Mathematical and Computational Modeling in Complex Biological Systems.

PubMed

Ji, Zhiwei; Yan, Ke; Li, Wenyang; Hu, Haigen; Zhu, Xiaoliang

2017-01-01

The biological process and molecular functions involved in the cancer progression remain difficult to understand for biologists and clinical doctors. Recent developments in high-throughput technologies urge the systems biology to achieve more precise models for complex diseases. Computational and mathematical models are gradually being used to help us understand the omics data produced by high-throughput experimental techniques. The use of computational models in systems biology allows us to explore the pathogenesis of complex diseases, improve our understanding of the latent molecular mechanisms, and promote treatment strategy optimization and new drug discovery. Currently, it is urgent to bridge the gap between the developments of high-throughput technologies and systemic modeling of the biological process in cancer research. In this review, we firstly studied several typical mathematical modeling approaches of biological systems in different scales and deeply analyzed their characteristics, advantages, applications, and limitations. Next, three potential research directions in systems modeling were summarized. To conclude, this review provides an update of important solutions using computational modeling approaches in systems biology.

Integrating systems biology models and biomedical ontologies

PubMed Central

2011-01-01

Background Systems biology is an approach to biology that emphasizes the structure and dynamic behavior of biological systems and the interactions that occur within them. To succeed, systems biology crucially depends on the accessibility and integration of data across domains and levels of granularity. Biomedical ontologies were developed to facilitate such an integration of data and are often used to annotate biosimulation models in systems biology. Results We provide a framework to integrate representations of in silico systems biology with those of in vivo biology as described by biomedical ontologies and demonstrate this framework using the Systems Biology Markup Language. We developed the SBML Harvester software that automatically converts annotated SBML models into OWL and we apply our software to those biosimulation models that are contained in the BioModels Database. We utilize the resulting knowledge base for complex biological queries that can bridge levels of granularity, verify models based on the biological phenomenon they represent and provide a means to establish a basic qualitative layer on which to express the semantics of biosimulation models. Conclusions We establish an information flow between biomedical ontologies and biosimulation models and we demonstrate that the integration of annotated biosimulation models and biomedical ontologies enables the verification of models as well as expressive queries. Establishing a bi-directional information flow between systems biology and biomedical ontologies has the potential to enable large-scale analyses of biological systems that span levels of granularity from molecules to organisms. PMID:21835028

Characterising the Development of the Understanding of Human Body Systems in High-School Biology Students--A Longitudinal Study

ERIC Educational Resources Information Center

Snapir, Zohar; Eberbach, Catherine; Ben-Zvi-Assaraf, Orit; Hmelo-Silver, Cindy; Tripto, Jaklin

2017-01-01

Science education today has become increasingly focused on research into complex natural, social and technological systems. In this study, we examined the development of high-school biology students' systems understanding of the human body, in a three-year longitudinal study. The development of the students' system understanding was evaluated…

Modeling for Visual Feature Extraction Using Spiking Neural Networks

NASA Astrophysics Data System (ADS)

Kimura, Ichiro; Kuroe, Yasuaki; Kotera, Hiromichi; Murata, Tomoya

This paper develops models for “visual feature extraction” in biological systems by using “spiking neural network (SNN)”. The SNN is promising for developing the models because the information is encoded and processed by spike trains similar to biological neural networks. Two architectures of SNN are proposed for modeling the directionally selective and the motion parallax cell in neuro-sensory systems and they are trained so as to possess actual biological responses of each cell. To validate the developed models, their representation ability is investigated and their visual feature extraction mechanisms are discussed from the neurophysiological viewpoint. It is expected that this study can be the first step to developing a sensor system similar to the biological systems and also a complementary approach to investigating the function of the brain.

A Personal Journey of Discovery: Developing Technology and Changing Biology

NASA Astrophysics Data System (ADS)

Hood, Lee

2008-07-01

This autobiographical article describes my experiences in developing chemically based, biological technologies for deciphering biological information: DNA, RNA, proteins, interactions, and networks. The instruments developed include protein and DNA sequencers and synthesizers, as well as ink-jet technology for synthesizing DNA chips. Diverse new strategies for doing biology also arose from novel applications of these instruments. The functioning of these instruments can be integrated to generate powerful new approaches to cloning and characterizing genes from a small amount of protein sequence or to using gene sequences to synthesize peptide fragments so as to characterize various properties of the proteins. I also discuss the five paradigm changes in which I have participated: the development and integration of biological instrumentation; the human genome project; cross-disciplinary biology; systems biology; and predictive, personalized, preventive, and participatory (P4) medicine. Finally, I discuss the origins, the philosophy, some accomplishments, and the future trajectories of the Institute for Systems Biology.

Illustrations of mathematical modeling in biology: epigenetics, meiosis, and an outlook.

PubMed

Richards, D; Berry, S; Howard, M

2012-01-01

In the past few years, mathematical modeling approaches in biology have begun to fulfill their promise by assisting in the dissection of complex biological systems. Here, we review two recent examples of predictive mathematical modeling in plant biology. The first involves the quantitative epigenetic silencing of the floral repressor gene FLC in Arabidopsis, mediated by a Polycomb-based system. The second involves the spatiotemporal dynamics of telomere bouquet formation in wheat-rye meiosis. Although both the biology and the modeling framework of the two systems are different, both exemplify how mathematical modeling can help to accelerate discovery of the underlying mechanisms in complex biological systems. In both cases, the models that developed were relatively minimal, including only essential features, but both nevertheless yielded fundamental insights. We also briefly review the current state of mathematical modeling in biology, difficulties inherent in its application, and its potential future development.

Applying differential dynamic logic to reconfigurable biological networks.

PubMed

Figueiredo, Daniel; Martins, Manuel A; Chaves, Madalena

2017-09-01

Qualitative and quantitative modeling frameworks are widely used for analysis of biological regulatory networks, the former giving a preliminary overview of the system's global dynamics and the latter providing more detailed solutions. Another approach is to model biological regulatory networks as hybrid systems, i.e., systems which can display both continuous and discrete dynamic behaviors. Actually, the development of synthetic biology has shown that this is a suitable way to think about biological systems, which can often be constructed as networks with discrete controllers, and present hybrid behaviors. In this paper we discuss this approach as a special case of the reconfigurability paradigm, well studied in Computer Science (CS). In CS there are well developed computational tools to reason about hybrid systems. We argue that it is worth applying such tools in a biological context. One interesting tool is differential dynamic logic (dL), which has recently been developed by Platzer and applied to many case-studies. In this paper we discuss some simple examples of biological regulatory networks to illustrate how dL can be used as an alternative, or also as a complement to methods already used. Copyright © 2017 Elsevier Inc. All rights reserved.

Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases.

PubMed

Oh, Soo Jin; Choi, Young Ki; Shin, Ok Sarah

2018-03-01

Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs. © Copyright: Yonsei University College of Medicine 2018.

Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases

PubMed Central

2018-01-01

Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs. PMID:29436184

A new organismal systems biology: how animals walk the tight rope between stability and change.

PubMed

Padilla, Dianna K; Tsukimura, Brian

2014-07-01

The amount of knowledge in the biological sciences is growing at an exponential rate. Simultaneously, the incorporation of new technologies in gathering scientific information has greatly accelerated our capacity to ask, and answer, new questions. How do we, as organismal biologists, meet these challenges, and develop research strategies that will allow us to address the grand challenge question: how do organisms walk the tightrope between stability and change? Organisms and organismal systems are complex, and multi-scale in both space and time. It is clear that addressing major questions about organismal biology will not come from "business as usual" approaches. Rather, we require the collaboration of a wide range of experts and integration of biological information with more quantitative approaches traditionally found in engineering and applied mathematics. Research programs designed to address grand challenge questions will require deep knowledge and expertise within subfields of organismal biology, collaboration and integration among otherwise disparate areas of research, and consideration of organisms as integrated systems. Our ability to predict which features of complex integrated systems provide the capacity to be robust in changing environments is poorly developed. A predictive organismal biology is needed, but will require more quantitative approaches than are typical in biology, including complex systems-modeling approaches common to engineering. This new organismal systems biology will have reciprocal benefits for biologists, engineers, and mathematicians who address similar questions, including those working on control theory and dynamical systems biology, and will develop the tools we need to address the grand challenge questions of the 21st century. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Evolving a lingua franca and associated software infrastructure for computational systems biology: the Systems Biology Markup Language (SBML) project.

PubMed

Hucka, M; Finney, A; Bornstein, B J; Keating, S M; Shapiro, B E; Matthews, J; Kovitz, B L; Schilstra, M J; Funahashi, A; Doyle, J C; Kitano, H

2004-06-01

Biologists are increasingly recognising that computational modelling is crucial for making sense of the vast quantities of complex experimental data that are now being collected. The systems biology field needs agreed-upon information standards if models are to be shared, evaluated and developed cooperatively. Over the last four years, our team has been developing the Systems Biology Markup Language (SBML) in collaboration with an international community of modellers and software developers. SBML has become a de facto standard format for representing formal, quantitative and qualitative models at the level of biochemical reactions and regulatory networks. In this article, we summarise the current and upcoming versions of SBML and our efforts at developing software infrastructure for supporting and broadening its use. We also provide a brief overview of the many SBML-compatible software tools available today.

Industrial systems biology and its impact on synthetic biology of yeast cell factories.

PubMed

Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

2016-06-01

Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal of developing improved yeast cell factories. Biotechnol. Bioeng. 2016;113: 1164-1170. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Min Zhang | NREL

Science.gov Websites

Min Zhang Photo of Min Zhang Min Zhang Researcher V-Molecular Biology Min.Zhang@nrel.gov | 303-384 -7753 Research Interests Using a systems biology approach to identify, analyze, and engineer pathways Metabolic engineering Molecular biology Microbial physiology Systems biology Fermentation development Enzyme

Molecular communication and networking: opportunities and challenges.

PubMed

Nakano, Tadashi; Moore, Michael J; Wei, Fang; Vasilakos, Athanasios V; Shuai, Jianwei

2012-06-01

The ability of engineered biological nanomachines to communicate with biological systems at the molecular level is anticipated to enable future applications such as monitoring the condition of a human body, regenerating biological tissues and organs, and interfacing artificial devices with neural systems. From the viewpoint of communication theory and engineering, molecular communication is proposed as a new paradigm for engineered biological nanomachines to communicate with the natural biological nanomachines which form a biological system. Distinct from the current telecommunication paradigm, molecular communication uses molecules as the carriers of information; sender biological nanomachines encode information on molecules and release the molecules in the environment, the molecules then propagate in the environment to receiver biological nanomachines, and the receiver biological nanomachines biochemically react with the molecules to decode information. Current molecular communication research is limited to small-scale networks of several biological nanomachines. Key challenges to bridge the gap between current research and practical applications include developing robust and scalable techniques to create a functional network from a large number of biological nanomachines. Developing networking mechanisms and communication protocols is anticipated to introduce new avenues into integrating engineered and natural biological nanomachines into a single networked system. In this paper, we present the state-of-the-art in the area of molecular communication by discussing its architecture, features, applications, design, engineering, and physical modeling. We then discuss challenges and opportunities in developing networking mechanisms and communication protocols to create a network from a large number of bio-nanomachines for future applications.

Microbial Development and Metabolic Engineering | Bioenergy | NREL

Science.gov Websites

beaker filled with a green liquid cyanobacteria culture that is bubbling. Synthetic Biology We have utilized the power of synthetic biology to uncover relevant genetic factors to predictably regulate gene operating a gas chromatograph mass spectrometer. Systems Biology Our comprehensive systems biology

No Time To Kill: Entrainment and Accelerating Courseware Development.

ERIC Educational Resources Information Center

Millington, Paula Crnkovich

This paper examines the concept of time in multimedia, World Wide Web-based courseware development. The biological concept of entrainment (the alignment of rhythms within and between systems) to accelerate courseware development is explored. The discussion begins with the foundational concepts of entrainment from biological systems and social…

Systems biology for molecular life sciences and its impact in biomedicine.

PubMed

Medina, Miguel Ángel

2013-03-01

Modern systems biology is already contributing to a radical transformation of molecular life sciences and biomedicine, and it is expected to have a real impact in the clinical setting in the next years. In this review, the emergence of systems biology is contextualized with a historic overview, and its present state is depicted. The present and expected future contribution of systems biology to the development of molecular medicine is underscored. Concerning the present situation, this review includes a reflection on the "inflation" of biological data and the urgent need for tools and procedures to make hidden information emerge. Descriptions of the impact of networks and models and the available resources and tools for applying them in systems biology approaches to molecular medicine are provided as well. The actual current impact of systems biology in molecular medicine is illustrated, reviewing two cases, namely, those of systems pharmacology and cancer systems biology. Finally, some of the expected contributions of systems biology to the immediate future of molecular medicine are commented.

Evaluation and modeling of HIV based on communication theory in biological systems.

PubMed

Dong, Miaowu; Li, Wenrong; Xu, Xi

2016-12-01

Some forms of communication are used in biological systems such as HIV transmission in human beings. In this paper, we plan to get a unique insight into biological communication systems generally through the analogy between HIV infection and electrical communication system. The model established in this paper can be used to test and simulate various communication systems since it provides researchers with an opportunity. We interpret biological communication systems by using telecommunications exemplification from a layered communication protocol developed before and use the model to indicate HIV spreading. We also implement a simulation of HIV infection based on the layered communication protocol to predict the development of this disease and the results prove the validity of the model. Copyright © 2016 Elsevier B.V. All rights reserved.

Genome Scale Modeling in Systems Biology: Algorithms and Resources

PubMed Central

Najafi, Ali; Bidkhori, Gholamreza; Bozorgmehr, Joseph H.; Koch, Ina; Masoudi-Nejad, Ali

2014-01-01

In recent years, in silico studies and trial simulations have complemented experimental procedures. A model is a description of a system, and a system is any collection of interrelated objects; an object, moreover, is some elemental unit upon which observations can be made but whose internal structure either does not exist or is ignored. Therefore, any network analysis approach is critical for successful quantitative modeling of biological systems. This review highlights some of most popular and important modeling algorithms, tools, and emerging standards for representing, simulating and analyzing cellular networks in five sections. Also, we try to show these concepts by means of simple example and proper images and graphs. Overall, systems biology aims for a holistic description and understanding of biological processes by an integration of analytical experimental approaches along with synthetic computational models. In fact, biological networks have been developed as a platform for integrating information from high to low-throughput experiments for the analysis of biological systems. We provide an overview of all processes used in modeling and simulating biological networks in such a way that they can become easily understandable for researchers with both biological and mathematical backgrounds. Consequently, given the complexity of generated experimental data and cellular networks, it is no surprise that researchers have turned to computer simulation and the development of more theory-based approaches to augment and assist in the development of a fully quantitative understanding of cellular dynamics. PMID:24822031

Probing Gravitational Sensitivity in Biological Systems Using Magnetic Body Forces

NASA Technical Reports Server (NTRS)

Guevorkian, Karine; Wurzel, Sam; Mihalusova, Mariana; Valles, Jim

2003-01-01

At Brown University, we are developing the use of magnetic body forces as a means to simulate variable gravity body forces on biological systems. This tool promises new means to probe gravi-sensing and the gravi-response of biological systems. It also has the potential as a technique for screening future systems for space flight experiments.

Consistent design schematics for biological systems: standardization of representation in biological engineering

PubMed Central

Matsuoka, Yukiko; Ghosh, Samik; Kitano, Hiroaki

2009-01-01

The discovery by design paradigm driving research in synthetic biology entails the engineering of de novo biological constructs with well-characterized input–output behaviours and interfaces. The construction of biological circuits requires iterative phases of design, simulation and assembly, leading to the fabrication of a biological device. In order to represent engineered models in a consistent visual format and further simulating them in silico, standardization of representation and model formalism is imperative. In this article, we review different efforts for standardization, particularly standards for graphical visualization and simulation/annotation schemata adopted in systems biology. We identify the importance of integrating the different standardization efforts and provide insights into potential avenues for developing a common framework for model visualization, simulation and sharing across various tools. We envision that such a synergistic approach would lead to the development of global, standardized schemata in biology, empowering deeper understanding of molecular mechanisms as well as engineering of novel biological systems. PMID:19493898

Studying Plant-Rhizobium Mutualism in the Biology Classroom: Connecting the Big Ideas in Biology through Inquiry

ERIC Educational Resources Information Center

Suwa, Tomomi; Williamson, Brad

2014-01-01

We present a guided-inquiry biology lesson, using the plant-rhizobium symbiosis as a model system. This system provides a rich environment for developing connections between the big ideas in biology as outlined in the College Board's new AP Biology Curriculum. Students gain experience with the practice of scientific investigation, from…

Light microscopy applications in systems biology: opportunities and challenges

PubMed Central

2013-01-01

Biological systems present multiple scales of complexity, ranging from molecules to entire populations. Light microscopy is one of the least invasive techniques used to access information from various biological scales in living cells. The combination of molecular biology and imaging provides a bottom-up tool for direct insight into how molecular processes work on a cellular scale. However, imaging can also be used as a top-down approach to study the behavior of a system without detailed prior knowledge about its underlying molecular mechanisms. In this review, we highlight the recent developments on microscopy-based systems analyses and discuss the complementary opportunities and different challenges with high-content screening and high-throughput imaging. Furthermore, we provide a comprehensive overview of the available platforms that can be used for image analysis, which enable community-driven efforts in the development of image-based systems biology. PMID:23578051

Quantitative Genetic Interactions Reveal Layers of Biological Modularity

PubMed Central

Beltrao, Pedro; Cagney, Gerard; Krogan, Nevan J.

2010-01-01

In the past, biomedical research has embraced a reductionist approach, primarily focused on characterizing the individual components that comprise a system of interest. Recent technical developments have significantly increased the size and scope of data describing biological systems. At the same time, advances in the field of systems biology have evoked a broader view of how the underlying components are interconnected. In this essay, we discuss how quantitative genetic interaction mapping has enhanced our view of biological systems, allowing a deeper functional interrogation at different biological scales. PMID:20510918

Emerging Tools for Synthetic Genome Design

PubMed Central

Lee, Bo-Rahm; Cho, Suhyung; Song, Yoseb; Kim, Sun Chang; Cho, Byung-Kwan

2013-01-01

Synthetic biology is an emerging discipline for designing and synthesizing predictable, measurable, controllable, and transformable biological systems. These newly designed biological systems have great potential for the development of cheaper drugs, green fuels, biodegradable plastics, and targeted cancer therapies over the coming years. Fortunately, our ability to quickly and accurately engineer biological systems that behave predictably has been dramatically expanded by significant advances in DNA-sequencing, DNA-synthesis, and DNA-editing technologies. Here, we review emerging technologies and methodologies in the field of building designed biological systems, and we discuss their future perspectives. PMID:23708771

ENFIN a network to enhance integrative systems biology.

PubMed

Kahlem, Pascal; Birney, Ewan

2007-12-01

Integration of biological data of various types and development of adapted bioinformatics tools represent critical objectives to enable research at the systems level. The European Network of Excellence ENFIN is engaged in developing both an adapted infrastructure to connect databases and platforms to enable the generation of new bioinformatics tools as well as the experimental validation of computational predictions. We will give an overview of the projects tackled within ENFIN and discuss the challenges associated with integration for systems biology.

Reconstructing Anaximander's biological model unveils a theory of evolution akin to Darwin's, though centuries before the birth of science.

PubMed

Trevisanato, Siro Igino

2016-08-01

Anaximander's fragments on biology report a theory of evolution, which, unlike the development of other biological systems in the ancient Aegean, is naturalistic and is not based on metaphysics. According to Anaximander, evolution affected all living beings, including humans. The first biological systems formed in an aquatic environment, and were encased in a rugged and robust envelope. Evolution progressed with modifications that enabled the formation of more dynamic biological systems. For instance, after reaching land, the robust armors around aquatic beings dried up, and became brittle, This led to the loss of the armor and the development of more mobile life forms. Anaximander's theory combines observations of animals with speculations, and as such mirrors the more famous theory of evolution by Charles Darwin expressed 24 centuries later. The poor reception received by Anaximander's model in his time, illustrates a zeitgeist that would explain the contemporary lag phase in the development of biology and, as a result, medicine, in the ancient western world.

Scaffolded biology.

PubMed

Minelli, Alessandro

2016-09-01

Descriptions and interpretations of the natural world are dominated by dichotomies such as organism vs. environment, nature vs. nurture, genetic vs. epigenetic, but in the last couple of decades strong dissatisfaction with those partitions has been repeatedly voiced and a number of alternative perspectives have been suggested, from perspectives such as Dawkins' extended phenotype, Turner's extended organism, Oyama's Developmental Systems Theory and Odling-Smee's niche construction theory. Last in time is the description of biological phenomena in terms of hybrids between an organism (scaffolded system) and a living or non-living scaffold, forming unit systems to study processes such as reproduction and development. As scaffold, eventually, we can define any resource used by the biological system, especially in development and reproduction, without incorporating it as happens in the case of resources fueling metabolism. Addressing biological systems as functionally scaffolded systems may help pointing to functional relationships that can impart temporal marking to the developmental process and thus explain its irreversibility; revisiting the boundary between development and metabolism and also regeneration phenomena, by suggesting a conceptual framework within which to investigate phenomena of regular hypermorphic regeneration such as characteristic of deer antlers; fixing a periodization of development in terms of the times at which a scaffolding relationship begins or is terminated; and promoting plant galls to legitimate study objects of developmental biology.

Web-based applications for building, managing and analysing kinetic models of biological systems.

PubMed

Lee, Dong-Yup; Saha, Rajib; Yusufi, Faraaz Noor Khan; Park, Wonjun; Karimi, Iftekhar A

2009-01-01

Mathematical modelling and computational analysis play an essential role in improving our capability to elucidate the functions and characteristics of complex biological systems such as metabolic, regulatory and cell signalling pathways. The modelling and concomitant simulation render it possible to predict the cellular behaviour of systems under various genetically and/or environmentally perturbed conditions. This motivates systems biologists/bioengineers/bioinformaticians to develop new tools and applications, allowing non-experts to easily conduct such modelling and analysis. However, among a multitude of systems biology tools developed to date, only a handful of projects have adopted a web-based approach to kinetic modelling. In this report, we evaluate the capabilities and characteristics of current web-based tools in systems biology and identify desirable features, limitations and bottlenecks for further improvements in terms of usability and functionality. A short discussion on software architecture issues involved in web-based applications and the approaches taken by existing tools is included for those interested in developing their own simulation applications.

Autonomous biological system-an unique method of conducting long duration space flight experiments for pharmaceutical and gravitational biology research

NASA Astrophysics Data System (ADS)

Anderson, G. A.; MacCallum, T. K.; Poynter, J. E.; Klaus, D., Dr.

1998-01-01

Paragon Space Development Corporation (SDC) has developed an Autonomous Biological System (ABS) that can be flown in space to provide for long term growth and breeding of aquatic plants, animals, microbes and algae. The system functions autonomously and in isolation from the spacecraft life support systems and with no mandatory crew time required for function or observation. The ABS can also be used for long term plant and animal life support and breeding on a free flyer space craft. The ABS units are a research tool for both pharmaceutical and basic space biological sciences. Development flights in May of 1996 and September, 1996 through January, 1997 were largely successful, showing both that the hardware and life systems are performing with beneficial results, though some surprises were still found. The two space flights, plus the current flight now on Mir, are expected to result in both a scientific and commercially usable system for breeding and propagation of animals and plants in space.

Modeling and simulation of biological systems using SPICE language

PubMed Central

Lallement, Christophe; Haiech, Jacques

2017-01-01

The article deals with BB-SPICE (SPICE for Biochemical and Biological Systems), an extension of the famous Simulation Program with Integrated Circuit Emphasis (SPICE). BB-SPICE environment is composed of three modules: a new textual and compact description formalism for biological systems, a converter that handles this description and generates the SPICE netlist of the equivalent electronic circuit and NGSPICE which is an open-source SPICE simulator. In addition, the environment provides back and forth interfaces with SBML (System Biology Markup Language), a very common description language used in systems biology. BB-SPICE has been developed in order to bridge the gap between the simulation of biological systems on the one hand and electronics circuits on the other hand. Thus, it is suitable for applications at the interface between both domains, such as development of design tools for synthetic biology and for the virtual prototyping of biosensors and lab-on-chip. Simulation results obtained with BB-SPICE and COPASI (an open-source software used for the simulation of biochemical systems) have been compared on a benchmark of models commonly used in systems biology. Results are in accordance from a quantitative viewpoint but BB-SPICE outclasses COPASI by 1 to 3 orders of magnitude regarding the computation time. Moreover, as our software is based on NGSPICE, it could take profit of incoming updates such as the GPU implementation, of the coupling with powerful analysis and verification tools or of the integration in design automation tools (synthetic biology). PMID:28787027

Recent perspectives on the delivery of biologics to back of the eye

PubMed Central

Joseph, Mary; Trinh, Hoang M.; Cholkar, Kishore; Pal, Dhananjay; Mitra, Ashim K.

2017-01-01

Introduction Biologics are generally macromolecules, large in size with poor stability in biological environments. Delivery of biologics to tissues at the back of the eye remains a challenge. To overcome these challenges and treat posterior ocular diseases, several novel approaches have been developed. Nanotechnology-based delivery systems, like drug encapsulation technology, macromolecule implants and gene delivery are under investigation. We provide an overview of emerging technologies for biologics delivery to back of the eye tissues. Moreover, new biologic drugs currently in clinical trials for ocular neovascular diseases have been discussed. Areas Covered Anatomy of the eye, posterior segment disease and diagnosis, barriers to biologic delivery, ocular pharmacokinetic, novel biologic delivery system Expert Opinion Anti-VEGF therapy represents a significant advance in developing biologics for the treatment of ocular neovascular diseases. Various strategies for biologic delivery to posterior ocular tissues are under development with some in early or late stages of clinical trials. Despite significant progress in the delivery of biologics, there is unmet need to develop sustained delivery of biologics with nearly zero-order release kinetics to the back of the eye tissues. In addition, elevated intraocular pressure associated with frequent intravitreal injections of macromolecules is another concern that needs to be addressed. PMID:27573097

Coupling biology and oceanography in models.

PubMed

Fennel, W; Neumann, T

2001-08-01

The dynamics of marine ecosystems, i.e. the changes of observable chemical-biological quantities in space and time, are driven by biological and physical processes. Predictions of future developments of marine systems need a theoretical framework, i.e. models, solidly based on research and understanding of the different processes involved. The natural way to describe marine systems theoretically seems to be the embedding of chemical-biological models into circulation models. However, while circulation models are relatively advanced the quantitative theoretical description of chemical-biological processes lags behind. This paper discusses some of the approaches and problems in the development of consistent theories and indicates the beneficial potential of the coupling of marine biology and oceanography in models.

The Spring of Systems Biology-Driven Breeding.

PubMed

Lavarenne, Jérémy; Guyomarc'h, Soazig; Sallaud, Christophe; Gantet, Pascal; Lucas, Mikaël

2018-05-12

Genetics and molecular biology have contributed to the development of rationalized plant breeding programs. Recent developments in both high-throughput experimental analyses of biological systems and in silico data processing offer the possibility to address the whole gene regulatory network (GRN) controlling a given trait. GRN models can be applied to identify topological features helping to shortlist potential candidate genes for breeding purposes. Time-series data sets can be used to support dynamic modelling of the network. This will enable a deeper comprehension of network behaviour and the identification of the few elements to be genetically rewired to push the system towards a modified phenotype of interest. This paves the way to design more efficient, systems biology-based breeding strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Specifications of Standards in Systems and Synthetic Biology.

PubMed

Schreiber, Falk; Bader, Gary D; Golebiewski, Martin; Hucka, Michael; Kormeier, Benjamin; Le Novère, Nicolas; Myers, Chris; Nickerson, David; Sommer, Björn; Waltemath, Dagmar; Weise, Stephan

2015-09-04

Standards shape our everyday life. From nuts and bolts to electronic devices and technological processes, standardised products and processes are all around us. Standards have technological and economic benefits, such as making information exchange, production, and services more efficient. However, novel, innovative areas often either lack proper standards, or documents about standards in these areas are not available from a centralised platform or formal body (such as the International Standardisation Organisation). Systems and synthetic biology is a relatively novel area, and it is only in the last decade that the standardisation of data, information, and models related to systems and synthetic biology has become a community-wide effort. Several open standards have been established and are under continuous development as a community initiative. COMBINE, the ‘COmputational Modeling in BIology’ NEtwork has been established as an umbrella initiative to coordinate and promote the development of the various community standards and formats for computational models. There are yearly two meeting, HARMONY (Hackathons on Resources for Modeling in Biology), Hackathon-type meetings with a focus on development of the support for standards, and COMBINE forums, workshop-style events with oral presentations, discussion, poster, and breakout sessions for further developing the standards. For more information see http://co.mbine.org/. So far the different standards were published and made accessible through the standards’ web- pages or preprint services. The aim of this special issue is to provide a single, easily accessible and citable platform for the publication of standards in systems and synthetic biology. This special issue is intended to serve as a central access point to standards and related initiatives in systems and synthetic biology, it will be published annually to provide an opportunity for standard development groups to communicate updated specifications.

Development of biological control of Tetranychus urticae (Acari:Tetranychidae) and Phorodon humuli (Hemiptera: Aphididae) in Oregon Hop yards

USDA-ARS?s Scientific Manuscript database

The temporal development of biological control of arthropod pests in perennial cropping systems is largely unreported. In this study, the development of biological control of twospotted spider mite, Tetranychus urticae Koch and hop aphid, Phorodon humuli (Schrank) in a new planting of hop in Oregon...

Advances in systems biology: computational algorithms and applications.

PubMed

Huang, Yufei; Zhao, Zhongming; Xu, Hua; Shyr, Yu; Zhang, Bing

2012-01-01

The 2012 International Conference on Intelligent Biology and Medicine (ICIBM 2012) was held on April 22-24, 2012 in Nashville, Tennessee, USA. The conference featured six technical sessions, one tutorial session, one workshop, and 3 keynote presentations that covered state-of-the-art research activities in genomics, systems biology, and intelligent computing. In addition to a major emphasis on the next generation sequencing (NGS)-driven informatics, ICIBM 2012 aligned significant interests in systems biology and its applications in medicine. We highlight in this editorial the selected papers from the meeting that address the developments of novel algorithms and applications in systems biology.

Guidelines for Developing Successful Short Advanced Courses in Systems Medicine and Systems Biology.

PubMed

Gomez-Cabrero, David; Marabita, Francesco; Tarazona, Sonia; Cano, Isaac; Roca, Josep; Conesa, Ana; Sabatier, Philippe; Tegnér, Jesper

2017-09-27

Systems medicine and systems biology have inherent educational challenges. These have largely been addressed either by providing new masters programs or by redesigning undergraduate programs. In contrast, short courses can respond to a different need: they can provide condensed updates for professionals across academia, the clinic, and industry. These courses have received less attention. Here, we share our experiences in developing and providing such courses to current and future leaders in systems biology and systems medicine. We present guidelines for how to reproduce our courses, and we offer suggestions for how to select students who will nurture an interdisciplinary learning environment and thrive there. Copyright © 2017 Elsevier Inc. All rights reserved.

New Tools and New Biology: Recent Miniaturized Systems for Molecular and Cellular Biology

PubMed Central

Hamon, Morgan; Hong, Jong Wook

2013-01-01

Recent advances in applied physics and chemistry have led to the development of novel microfluidic systems. Microfluidic systems allow minute amounts of reagents to be processed using μm-scale channels and offer several advantages over conventional analytical devices for use in biological sciences: faster, more accurate and more reproducible analytical performance, reduced cell and reagent consumption, portability, and integration of functional components in a single chip. In this review, we introduce how microfluidics has been applied to biological sciences. We first present an overview of the fabrication of microfluidic systems and describe the distinct technologies available for biological research. We then present examples of microsystems used in biological sciences, focusing on applications in molecular and cellular biology. PMID:24305843

The 'Biologically-Inspired Computing' Column

NASA Technical Reports Server (NTRS)

Hinchey, Mike

2006-01-01

The field of Biology changed dramatically in 1953, with the determination by Francis Crick and James Dewey Watson of the double helix structure of DNA. This discovery changed Biology for ever, allowing the sequencing of the human genome, and the emergence of a "new Biology" focused on DNA, genes, proteins, data, and search. Computational Biology and Bioinformatics heavily rely on computing to facilitate research into life and development. Simultaneously, an understanding of the biology of living organisms indicates a parallel with computing systems: molecules in living cells interact, grow, and transform according to the "program" dictated by DNA. Moreover, paradigms of Computing are emerging based on modelling and developing computer-based systems exploiting ideas that are observed in nature. This includes building into computer systems self-management and self-governance mechanisms that are inspired by the human body's autonomic nervous system, modelling evolutionary systems analogous to colonies of ants or other insects, and developing highly-efficient and highly-complex distributed systems from large numbers of (often quite simple) largely homogeneous components to reflect the behaviour of flocks of birds, swarms of bees, herds of animals, or schools of fish. This new field of "Biologically-Inspired Computing", often known in other incarnations by other names, such as: Autonomic Computing, Pervasive Computing, Organic Computing, Biomimetics, and Artificial Life, amongst others, is poised at the intersection of Computer Science, Engineering, Mathematics, and the Life Sciences. Successes have been reported in the fields of drug discovery, data communications, computer animation, control and command, exploration systems for space, undersea, and harsh environments, to name but a few, and augur much promise for future progress.

Frontiers of optofluidics in synthetic biology.

PubMed

Tan, Cheemeng; Lo, Shih-Jie; LeDuc, Philip R; Cheng, Chao-Min

2012-10-07

The development of optofluidic-based technology has ushered in a new era of lab-on-a-chip functionality, including miniaturization of biomedical devices, enhanced sensitivity for molecular detection, and multiplexing of optical measurements. While having great potential, optofluidic devices have only begun to be exploited in many biotechnological applications. Here, we highlight the potential of integrating optofluidic devices with synthetic biological systems, which is a field focusing on creating novel cellular systems by engineering synthetic gene and protein networks. First, we review the development of synthetic biology at different length scales, ranging from single-molecule, single-cell, to cellular population. We emphasize light-sensitive synthetic biological systems that would be relevant for the integration with optofluidic devices. Next, we propose several areas for potential applications of optofluidics in synthetic biology. The integration of optofluidics and synthetic biology would have a broad impact on point-of-care diagnostics and biotechnology.

Holarchical Systems and Emotional Holons : Biologically-Inspired System Designs for Control of Autonomous Aerial Vehicles

NASA Technical Reports Server (NTRS)

Ippolito, Corey; Plice, Laura; Pisanich, Greg

2003-01-01

The BEES (Bio-inspired Engineering for Exploration Systems) for Mars project at NASA Ames Research Center has the goal of developing bio-inspired flight control strategies to enable aerial explorers for Mars scientific investigations. This paper presents a summary of our ongoing research into biologically inspired system designs for control of unmanned autonomous aerial vehicle communities for Mars exploration. First, we present cooperative design considerations for robotic explorers based on the holarchical nature of biological systems and communities. Second, an outline of an architecture for cognitive decision making and control of individual robotic explorers is presented, modeled after the emotional nervous system of cognitive biological systems. Keywords: Holarchy, Biologically Inspired, Emotional UAV Flight Control

Network-based drug discovery by integrating systems biology and computational technologies

PubMed Central

Leung, Elaine L.; Cao, Zhi-Wei; Jiang, Zhi-Hong; Zhou, Hua

2013-01-01

Network-based intervention has been a trend of curing systemic diseases, but it relies on regimen optimization and valid multi-target actions of the drugs. The complex multi-component nature of medicinal herbs may serve as valuable resources for network-based multi-target drug discovery due to its potential treatment effects by synergy. Recently, robustness of multiple systems biology platforms shows powerful to uncover molecular mechanisms and connections between the drugs and their targeting dynamic network. However, optimization methods of drug combination are insufficient, owning to lacking of tighter integration across multiple ‘-omics’ databases. The newly developed algorithm- or network-based computational models can tightly integrate ‘-omics’ databases and optimize combinational regimens of drug development, which encourage using medicinal herbs to develop into new wave of network-based multi-target drugs. However, challenges on further integration across the databases of medicinal herbs with multiple system biology platforms for multi-target drug optimization remain to the uncertain reliability of individual data sets, width and depth and degree of standardization of herbal medicine. Standardization of the methodology and terminology of multiple system biology and herbal database would facilitate the integration. Enhance public accessible databases and the number of research using system biology platform on herbal medicine would be helpful. Further integration across various ‘-omics’ platforms and computational tools would accelerate development of network-based drug discovery and network medicine. PMID:22877768

Systems Biology, Systems Medicine, Systems Pharmacology: The What and The Why.

PubMed

Stéphanou, Angélique; Fanchon, Eric; Innominato, Pasquale F; Ballesta, Annabelle

2018-05-09

Systems biology is today such a widespread discipline that it becomes difficult to propose a clear definition of what it really is. For some, it remains restricted to the genomic field. For many, it designates the integrated approach or the corpus of computational methods employed to handle the vast amount of biological or medical data and investigate the complexity of the living. Although defining systems biology might be difficult, on the other hand its purpose is clear: systems biology, with its emerging subfields systems medicine and systems pharmacology, clearly aims at making sense of complex observations/experimental and clinical datasets to improve our understanding of diseases and their treatments without putting aside the context in which they appear and develop. In this short review, we aim to specifically focus on these new subfields with the new theoretical tools and approaches that were developed in the context of cancer. Systems pharmacology and medicine now give hope for major improvements in cancer therapy, making personalized medicine closer to reality. As we will see, the current challenge is to be able to improve the clinical practice according to the paradigm shift of systems sciences.

Development and implementation of an expert system to improve the control of nitrification and denitrification in the Vic wastewater treatment plant.

PubMed

Ribas, F; Rodríguez-Roda, I; Serrat, J; Clara, P; Comas, J

2008-05-01

Wastewater treatment plants employ various physical, chemical and biological processes to reduce pollutants from raw wastewater. One of the most important is the biological nitrogen removal process through nitrification and denitrification steps taking place in various sections of the biological reactor. One of the most extensively used configurations to achieve the biological nitrogen removal is an activated sludge system using oxidation ditch or extended aeration. To improve nitrogen removal in the wastewater treatment plant (WWTP) of Vic (Catalonia, NE Spain), the automatic aeration control system was complemented with an Expert System to always provide the most appropriate aeration or anoxia sequence based on the values of ammonium and nitrates given by an automatic analyzer. This article illustrates the development and implementation of this knowledge-based system within the framework of a Decision Support System, which performs SCADA functions. The paper also shows that the application of the decision support system in the Vic WWTP resulted in significant improvements to the biological nitrogen removal.

Micro-separation toward systems biology.

PubMed

Liu, Bi-Feng; Xu, Bo; Zhang, Guisen; Du, Wei; Luo, Qingming

2006-02-17

Current biology is experiencing transformation in logic or philosophy that forces us to reevaluate the concept of cell, tissue or entire organism as a collection of individual components. Systems biology that aims at understanding biological system at the systems level is an emerging research area, which involves interdisciplinary collaborations of life sciences, computational and mathematical sciences, systems engineering, and analytical technology, etc. For analytical chemistry, developing innovative methods to meet the requirement of systems biology represents new challenges as also opportunities and responsibility. In this review, systems biology-oriented micro-separation technologies are introduced for comprehensive profiling of genome, proteome and metabolome, characterization of biomolecules interaction and single cell analysis such as capillary electrophoresis, ultra-thin layer gel electrophoresis, micro-column liquid chromatography, and their multidimensional combinations, parallel integrations, microfabricated formats, and nano technology involvement. Future challenges and directions are also suggested.

Revolution of Alzheimer Precision Neurology Passageway of Systems Biology and Neurophysiology.

PubMed

Hampel, Harald; Toschi, Nicola; Babiloni, Claudio; Baldacci, Filippo; Black, Keith L; Bokde, Arun L W; Bun, René S; Cacciola, Francesco; Cavedo, Enrica; Chiesa, Patrizia A; Colliot, Olivier; Coman, Cristina-Maria; Dubois, Bruno; Duggento, Andrea; Durrleman, Stanley; Ferretti, Maria-Teresa; George, Nathalie; Genthon, Remy; Habert, Marie-Odile; Herholz, Karl; Koronyo, Yosef; Koronyo-Hamaoui, Maya; Lamari, Foudil; Langevin, Todd; Lehéricy, Stéphane; Lorenceau, Jean; Neri, Christian; Nisticò, Robert; Nyasse-Messene, Francis; Ritchie, Craig; Rossi, Simone; Santarnecchi, Emiliano; Sporns, Olaf; Verdooner, Steven R; Vergallo, Andrea; Villain, Nicolas; Younesi, Erfan; Garaci, Francesco; Lista, Simone

2018-03-16

The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular, and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an "omics"-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical, and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer's disease. The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group "Alzheimer Precision Medicine" (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development toward breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND.

Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology

PubMed Central

Hampel, Harald; Toschi, Nicola; Babiloni, Claudio; Baldacci, Filippo; Black, Keith L.; Bokde, Arun L.W.; Bun, René S.; Cacciola, Francesco; Cavedo, Enrica; Chiesa, Patrizia A.; Colliot, Olivier; Coman, Cristina-Maria; Dubois, Bruno; Duggento, Andrea; Durrleman, Stanley; Ferretti, Maria-Teresa; George, Nathalie; Genthon, Remy; Habert, Marie-Odile; Herholz, Karl; Koronyo, Yosef; Koronyo-Hamaoui, Maya; Lamari, Foudil; Langevin, Todd; Lehéricy, Stéphane; Lorenceau, Jean; Neri, Christian; Nisticò, Robert; Nyasse-Messene, Francis; Ritchie, Craig; Rossi, Simone; Santarnecchi, Emiliano; Sporns, Olaf; Verdooner, Steven R.; Vergallo, Andrea; Villain, Nicolas; Younesi, Erfan; Garaci, Francesco; Lista, Simone

2018-01-01

The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an “omics”-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer’s disease (AD). The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group “Alzheimer Precision Medicine” (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development towards breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND. PMID:29562524

Wireless Biological Electronic Sensors.

PubMed

Cui, Yue

2017-10-09

The development of wireless biological electronic sensors could open up significant advances for both fundamental studies and practical applications in a variety of areas, including medical diagnosis, environmental monitoring, and defense applications. One of the major challenges in the development of wireless bioelectronic sensors is the successful integration of biosensing units and wireless signal transducers. In recent years, there are a few types of wireless communication systems that have been integrated with biosensing systems to construct wireless bioelectronic sensors. To successfully construct wireless biological electronic sensors, there are several interesting questions: What types of biosensing transducers can be used in wireless bioelectronic sensors? What types of wireless systems can be integrated with biosensing transducers to construct wireless bioelectronic sensors? How are the electrical sensing signals generated and transmitted? This review will highlight the early attempts to address these questions in the development of wireless biological electronic sensors.

Systems biology solutions for biochemical production challenges.

PubMed

Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus; Herrgård, Markus J

2017-06-01

There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains for biofuels and -chemicals. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Systems Biology for Smart Crops and Agricultural Innovation: Filling the Gaps between Genotype and Phenotype for Complex Traits Linked with Robust Agricultural Productivity and Sustainability

PubMed Central

Pathak, Rajesh Kumar; Gupta, Sanjay Mohan; Gaur, Vikram Singh; Pandey, Dinesh

2015-01-01

Abstract In recent years, rapid developments in several omics platforms and next generation sequencing technology have generated a huge amount of biological data about plants. Systems biology aims to develop and use well-organized and efficient algorithms, data structure, visualization, and communication tools for the integration of these biological data with the goal of computational modeling and simulation. It studies crop plant systems by systematically perturbing them, checking the gene, protein, and informational pathway responses; integrating these data; and finally, formulating mathematical models that describe the structure of system and its response to individual perturbations. Consequently, systems biology approaches, such as integrative and predictive ones, hold immense potential in understanding of molecular mechanism of agriculturally important complex traits linked to agricultural productivity. This has led to identification of some key genes and proteins involved in networks of pathways involved in input use efficiency, biotic and abiotic stress resistance, photosynthesis efficiency, root, stem and leaf architecture, and nutrient mobilization. The developments in the above fields have made it possible to design smart crops with superior agronomic traits through genetic manipulation of key candidate genes. PMID:26484978

How Is the Body's Systemic Nature Manifested amongst High School Biology Students?

ERIC Educational Resources Information Center

Tripto, Jaklin; Assaraf, Orit Ben; Snapir, Zohar; Amit, Miriam

2017-01-01

This study follows two groups of students (67 in all) through the 3 years of their high school biology education and examines the development of their systems thinking--specifically their models of the human body as a system. Both groups were composed of biology majors, but the students in one group also participated in a PBLbased extension…

When physics is not "just physics": complexity science invites new measurement frames for exploring the physics of cognitive and biological development.

PubMed

Kelty-Stephen, Damian; Dixon, James A

2012-01-01

The neurobiological sciences have struggled to resolve the physical foundations for biological and cognitive phenomena with a suspicion that biological and cognitive systems, capable of exhibiting and contributing to structure within themselves and through their contexts, are fundamentally distinct or autonomous from purely physical systems. Complexity science offers new physics-based approaches to explaining biological and cognitive phenomena. In response to controversy over whether complexity science might seek to "explain away" biology and cognition as "just physics," we propose that complexity science serves as an application of recent advances in physics to phenomena in biology and cognition without reducing or undermining the integrity of the phenomena to be explained. We highlight that physics is, like the neurobiological sciences, an evolving field and that the threat of reduction is overstated. We propose that distinctions between biological and cognitive systems from physical systems are pretheoretical and thus optional. We review our own work applying insights from post-classical physics regarding turbulence and fractal fluctuations to the problems of developing cognitive structure. Far from hoping to reduce biology and cognition to "nothing but" physics, we present our view that complexity science offers new explanatory frameworks for considering physical foundations of biological and cognitive phenomena.

Methods of information geometry in computational system biology (consistency between chemical and biological evolution).

PubMed

Astakhov, Vadim

2009-01-01

Interest in simulation of large-scale metabolic networks, species development, and genesis of various diseases requires new simulation techniques to accommodate the high complexity of realistic biological networks. Information geometry and topological formalisms are proposed to analyze information processes. We analyze the complexity of large-scale biological networks as well as transition of the system functionality due to modification in the system architecture, system environment, and system components. The dynamic core model is developed. The term dynamic core is used to define a set of causally related network functions. Delocalization of dynamic core model provides a mathematical formalism to analyze migration of specific functions in biosystems which undergo structure transition induced by the environment. The term delocalization is used to describe these processes of migration. We constructed a holographic model with self-poetic dynamic cores which preserves functional properties under those transitions. Topological constraints such as Ricci flow and Pfaff dimension were found for statistical manifolds which represent biological networks. These constraints can provide insight on processes of degeneration and recovery which take place in large-scale networks. We would like to suggest that therapies which are able to effectively implement estimated constraints, will successfully adjust biological systems and recover altered functionality. Also, we mathematically formulate the hypothesis that there is a direct consistency between biological and chemical evolution. Any set of causal relations within a biological network has its dual reimplementation in the chemistry of the system environment.

Plant Systems Biology at the Single-Cell Level.

PubMed

Libault, Marc; Pingault, Lise; Zogli, Prince; Schiefelbein, John

2017-11-01

Our understanding of plant biology is increasingly being built upon studies using 'omics and system biology approaches performed at the level of the entire plant, organ, or tissue. Although these approaches open new avenues to better understand plant biology, they suffer from the cellular complexity of the analyzed sample. Recent methodological advances now allow plant scientists to overcome this limitation and enable biological analyses of single-cells or single-cell-types. Coupled with the development of bioinformatics and functional genomics resources, these studies provide opportunities for high-resolution systems analyses of plant phenomena. In this review, we describe the recent advances, current challenges, and future directions in exploring the biology of single-cells and single-cell-types to enhance our understanding of plant biology as a system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Engineering scalable biological systems

PubMed Central

2010-01-01

Synthetic biology is focused on engineering biological organisms to study natural systems and to provide new solutions for pressing medical, industrial and environmental problems. At the core of engineered organisms are synthetic biological circuits that execute the tasks of sensing inputs, processing logic and performing output functions. In the last decade, significant progress has been made in developing basic designs for a wide range of biological circuits in bacteria, yeast and mammalian systems. However, significant challenges in the construction, probing, modulation and debugging of synthetic biological systems must be addressed in order to achieve scalable higher-complexity biological circuits. Furthermore, concomitant efforts to evaluate the safety and biocontainment of engineered organisms and address public and regulatory concerns will be necessary to ensure that technological advances are translated into real-world solutions. PMID:21468204

Designing mental health interventions informed by child development and human biology theory: A social ecology intervention for child soldiers in Nepal

PubMed Central

Kohrt, Brandon A.; Jordans, Mark J.D.; Koirala, Suraj; Worthman, Carol M.

2017-01-01

The anthropological study of human biology, health, and child development provides a model with potential to address the gap in population-wide mental health interventions. Four key concepts from human biology can inform public mental health interventions: life history theory and tradeoffs, redundancy and plurality of pathways, cascades and multiplier effects in biological systems, and proximate feedback systems. A public mental health intervention for former child soldiers in Nepal is used to illustrate the role of these concepts in intervention design and evaluation. Future directions and recommendations for applying human biology theory in pursuit of public mental health interventions are discussed. PMID:25380194

Designing mental health interventions informed by child development and human biology theory: a social ecology intervention for child soldiers in Nepal.

PubMed

Kohrt, Brandon A; Jordans, Mark J D; Koirala, Suraj; Worthman, Carol M

2015-01-01

The anthropological study of human biology, health, and child development provides a model with potential to address the gap in population-wide mental health interventions. Four key concepts from human biology can inform public mental health interventions: life history theory and tradeoffs, redundancy and plurality of pathways, cascades and multiplier effects in biological systems, and proximate feedback systems. A public mental health intervention for former child soldiers in Nepal is used to illustrate the role of these concepts in intervention design and evaluation. Future directions and recommendations for applying human biology theory in pursuit of public mental health interventions are discussed. © 2014 Wiley Periodicals, Inc.

Controlled biological and biomimetic systems for landmine detection.

PubMed

Habib, Maki K

2007-08-30

Humanitarian demining requires to accurately detect, locate and deactivate every single landmine and other buried mine-like objects as safely and as quickly as possible, and in the most non-invasive manner. The quality of landmine detection affects directly the efficiency and safety of this process. Most of the available methods to detect explosives and landmines are limited by their sensitivity and/or operational complexities. All landmines leak with time small amounts of their explosives that can be found on surrounding ground and plant life. Hence, explosive signatures represent the robust primary indicator of landmines. Accordingly, developing innovative technologies and efficient techniques to identify in real-time explosives residue in mined areas represents an attractive and promising approach. Biological and biologically inspired detection technology has the potential to compete with or be used in conjunction with other artificial technology to complement performance strengths. Biological systems are sensitive to many different scents concurrently, a property that has proven difficult to replicate artificially. Understanding biological systems presents unique opportunities for developing new capabilities through direct use of trained bio-systems, integration of living and non-living components, or inspiring new design by mimicking biological capabilities. It is expected that controlled bio-systems, biotechnology and microbial techniques will contribute to the advancement of mine detection and other application domains. This paper provides directions, evaluation and analysis on the progress of controlled biological and biomimetic systems for landmine detection. It introduces and discusses different approaches developed, underlining their relative advantages and limitations, and highlighting trends, safety and ecology concern, and possible future directions.

Synthetic Biology Open Language (SBOL) Version 2.0.0.

PubMed

Bartley, Bryan; Beal, Jacob; Clancy, Kevin; Misirli, Goksel; Roehner, Nicholas; Oberortner, Ernst; Pocock, Matthew; Bissell, Michael; Madsen, Curtis; Nguyen, Tramy; Zhang, Zhen; Gennari, John H; Myers, Chris; Wipat, Anil; Sauro, Herbert

2015-09-04

Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The Synthetic Biology Open Language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.0 of SBOL, introducing a standardized format for the electronic exchange of information on the structural and functional aspects of biological designs. The standard has been designed to support the explicit and unambiguous description of biological designs by means of a well defined data model. The standard also includes rules and best practices on how to use this data model and populate it with relevant design details. The publication of this specification is intended to make these capabilities more widely accessible to potential developers and users in the synthetic biology community and beyond.

Toward metabolic engineering in the context of system biology and synthetic biology: advances and prospects.

PubMed

Liu, Yanfeng; Shin, Hyun-dong; Li, Jianghua; Liu, Long

2015-02-01

Metabolic engineering facilitates the rational development of recombinant bacterial strains for metabolite overproduction. Building on enormous advances in system biology and synthetic biology, novel strategies have been established for multivariate optimization of metabolic networks in ensemble, spatial, and dynamic manners such as modular pathway engineering, compartmentalization metabolic engineering, and metabolic engineering guided by genome-scale metabolic models, in vitro reconstitution, and systems and synthetic biology. Herein, we summarize recent advances in novel metabolic engineering strategies. Combined with advancing kinetic models and synthetic biology tools, more efficient new strategies for improving cellular properties can be established and applied for industrially important biochemical production.

Synthetic biology: programming cells for biomedical applications.

PubMed

Hörner, Maximilian; Reischmann, Nadine; Weber, Wilfried

2012-01-01

The emerging field of synthetic biology is a novel biological discipline at the interface between traditional biology, chemistry, and engineering sciences. Synthetic biology aims at the rational design of complex synthetic biological devices and systems with desired properties by combining compatible, modular biological parts in a systematic manner. While the first engineered systems were mainly proof-of-principle studies to demonstrate the power of the modular engineering approach of synthetic biology, subsequent systems focus on applications in the health, environmental, and energy sectors. This review describes recent approaches for biomedical applications that were developed along the synthetic biology design hierarchy, at the level of individual parts, of devices, and of complex multicellular systems. It describes how synthetic biological parts can be used for the synthesis of drug-delivery tools, how synthetic biological devices can facilitate the discovery of novel drugs, and how multicellular synthetic ecosystems can give insight into population dynamics of parasites and hosts. These examples demonstrate how this new discipline could contribute to novel solutions in the biopharmaceutical industry.

Systems Modelling and the Development of Coherent Understanding of Cell Biology

ERIC Educational Resources Information Center

Verhoeff, Roald P.; Waarlo, Arend Jan; Boersma, Kerst Th.

2008-01-01

This article reports on educational design research concerning a learning and teaching strategy for cell biology in upper-secondary education introducing "systems modelling" as a key competence. The strategy consists of four modelling phases in which students subsequently develop models of free-living cells, a general two-dimensional model of…

Newton, Laplace, and The Epistemology of Systems Biology

PubMed Central

Bittner, Michael L.; Dougherty, Edward R.

2012-01-01

For science, theoretical or applied, to significantly advance, researchers must use the most appropriate mathematical methods. A century and a half elapsed between Newton’s development of the calculus and Laplace’s development of celestial mechanics. One cannot imagine the latter without the former. Today, more than three-quarters of a century has elapsed since the birth of stochastic systems theory. This article provides a perspective on the utilization of systems theory as the proper vehicle for the development of systems biology and its application to complex regulatory diseases such as cancer. PMID:23170064

Synthetic Biology and Microbial Fuel Cells: Towards Self-Sustaining Life Support Systems

NASA Technical Reports Server (NTRS)

Hogan, John Andrew

2014-01-01

NASA ARC and the J. Craig Venter Institute (JCVI) collaborated to investigate the development of advanced microbial fuels cells (MFCs) for biological wastewater treatment and electricity production (electrogenesis). Synthetic biology techniques and integrated hardware advances were investigated to increase system efficiency and robustness, with the intent of increasing power self-sufficiency and potential product formation from carbon dioxide. MFCs possess numerous advantages for space missions, including rapid processing, reduced biomass and effective removal of organics, nitrogen and phosphorus. Project efforts include developing space-based MFC concepts, integration analyses, increasing energy efficiency, and investigating novel bioelectrochemical system applications

Creating biological nanomaterials using synthetic biology.

PubMed

Rice, MaryJoe K; Ruder, Warren C

2014-02-01

Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

Quantum biology of the retina.

PubMed

Sia, Paul Ikgan; Luiten, André N; Stace, Thomas M; Wood, John Pm; Casson, Robert J

2014-08-01

The emerging field of quantum biology has led to a greater understanding of biological processes at the microscopic level. There is recent evidence to suggest that non-trivial quantum features such as entanglement, tunnelling and coherence have evolved in living systems. These quantum features are particularly evident in supersensitive light-harvesting systems such as in photosynthesis and photoreceptors. A biomimetic strategy utilizing biological quantum phenomena might allow new advances in the field of quantum engineering, particularly in quantum information systems. In addition, a better understanding of quantum biological features may lead to novel medical diagnostic and therapeutic developments. In the present review, we discuss the role of quantum physics in biological systems with an emphasis on the retina. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

Integration of systems biology with bioprocess engineering: L: -threonine production by systems metabolic engineering of Escherichia coli.

PubMed

Lee, Sang Yup; Park, Jin Hwan

2010-01-01

Random mutation and selection or targeted metabolic engineering without consideration of its impact on the entire metabolic and regulatory networks can unintentionally cause genetic alterations in the region, which is not directly related to the target metabolite. This is one of the reasons why strategies for developing industrial strains are now shifted towards targeted metabolic engineering based on systems biology, which is termed systems metabolic engineering. Using systems metabolic engineering strategies, all the metabolic engineering works are conducted in systems biology framework, whereby entire metabolic and regulatory networks are thoroughly considered in an integrated manner. The targets for purposeful engineering are selected after all possible effects on the entire metabolic and regulatory networks are thoroughly considered. Finally, the strain, which is capable of producing the target metabolite to a high level close to the theoretical maximum value, can be constructed. Here we review strategies and applications of systems biology successfully implemented on bioprocess engineering, with particular focus on developing L: -threonine production strains of Escherichia coli.

The "Biologically-Inspired Computing" Column

NASA Technical Reports Server (NTRS)

Hinchey, Mike

2007-01-01

Self-managing systems, whether viewed from the perspective of Autonomic Computing, or from that of another initiative, offers a holistic vision for the development and evolution of biologically-inspired computer-based systems. It aims to bring new levels of automation and dependability to systems, while simultaneously hiding their complexity and reducing costs. A case can certainly be made that all computer-based systems should exhibit autonomic properties [6], and we envisage greater interest in, and uptake of, autonomic principles in future system development.

Synthetic biology approaches in cancer immunotherapy, genetic network engineering, and genome editing.

PubMed

Chakravarti, Deboki; Cho, Jang Hwan; Weinberg, Benjamin H; Wong, Nicole M; Wong, Wilson W

2016-04-18

Investigations into cells and their contents have provided evolving insight into the emergence of complex biological behaviors. Capitalizing on this knowledge, synthetic biology seeks to manipulate the cellular machinery towards novel purposes, extending discoveries from basic science to new applications. While these developments have demonstrated the potential of building with biological parts, the complexity of cells can pose numerous challenges. In this review, we will highlight the broad and vital role that the synthetic biology approach has played in applying fundamental biological discoveries in receptors, genetic circuits, and genome-editing systems towards translation in the fields of immunotherapy, biosensors, disease models and gene therapy. These examples are evidence of the strength of synthetic approaches, while also illustrating considerations that must be addressed when developing systems around living cells.

Using argument notation to engineer biological simulations with increased confidence

PubMed Central

Alden, Kieran; Andrews, Paul S.; Polack, Fiona A. C.; Veiga-Fernandes, Henrique; Coles, Mark C.; Timmis, Jon

2015-01-01

The application of computational and mathematical modelling to explore the mechanics of biological systems is becoming prevalent. To significantly impact biological research, notably in developing novel therapeutics, it is critical that the model adequately represents the captured system. Confidence in adopting in silico approaches can be improved by applying a structured argumentation approach, alongside model development and results analysis. We propose an approach based on argumentation from safety-critical systems engineering, where a system is subjected to a stringent analysis of compliance against identified criteria. We show its use in examining the biological information upon which a model is based, identifying model strengths, highlighting areas requiring additional biological experimentation and providing documentation to support model publication. We demonstrate our use of structured argumentation in the development of a model of lymphoid tissue formation, specifically Peyer's Patches. The argumentation structure is captured using Artoo (www.york.ac.uk/ycil/software/artoo), our Web-based tool for constructing fitness-for-purpose arguments, using a notation based on the safety-critical goal structuring notation. We show how argumentation helps in making the design and structured analysis of a model transparent, capturing the reasoning behind the inclusion or exclusion of each biological feature and recording assumptions, as well as pointing to evidence supporting model-derived conclusions. PMID:25589574

Using argument notation to engineer biological simulations with increased confidence.

PubMed

Alden, Kieran; Andrews, Paul S; Polack, Fiona A C; Veiga-Fernandes, Henrique; Coles, Mark C; Timmis, Jon

2015-03-06

The application of computational and mathematical modelling to explore the mechanics of biological systems is becoming prevalent. To significantly impact biological research, notably in developing novel therapeutics, it is critical that the model adequately represents the captured system. Confidence in adopting in silico approaches can be improved by applying a structured argumentation approach, alongside model development and results analysis. We propose an approach based on argumentation from safety-critical systems engineering, where a system is subjected to a stringent analysis of compliance against identified criteria. We show its use in examining the biological information upon which a model is based, identifying model strengths, highlighting areas requiring additional biological experimentation and providing documentation to support model publication. We demonstrate our use of structured argumentation in the development of a model of lymphoid tissue formation, specifically Peyer's Patches. The argumentation structure is captured using Artoo (www.york.ac.uk/ycil/software/artoo), our Web-based tool for constructing fitness-for-purpose arguments, using a notation based on the safety-critical goal structuring notation. We show how argumentation helps in making the design and structured analysis of a model transparent, capturing the reasoning behind the inclusion or exclusion of each biological feature and recording assumptions, as well as pointing to evidence supporting model-derived conclusions.

Systems Biology of Industrial Microorganisms

NASA Astrophysics Data System (ADS)

Papini, Marta; Salazar, Margarita; Nielsen, Jens

The field of industrial biotechnology is expanding rapidly as the chemical industry is looking towards more sustainable production of chemicals that can be used as fuels or building blocks for production of solvents and materials. In connection with the development of sustainable bioprocesses, it is a major challenge to design and develop efficient cell factories that can ensure cost efficient conversion of the raw material into the chemical of interest. This is achieved through metabolic engineering, where the metabolism of the cell factory is engineered such that there is an efficient conversion of sugars, the typical raw materials in the fermentation industry, into the desired product. However, engineering of cellular metabolism is often challenging due to the complex regulation that has evolved in connection with adaptation of the different microorganisms to their ecological niches. In order to map these regulatory structures and further de-regulate them, as well as identify ingenious metabolic engineering strategies that full-fill mass balance constraints, tools from systems biology can be applied. This involves both high-throughput analysis tools like transcriptome, proteome and metabolome analysis, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies. It is in fact expected that systems biology may substantially improve the process of cell factory development, and we therefore propose the term Industrial Systems Biology for how systems biology will enhance the development of industrial biotechnology for sustainable chemical production.

Systems biology of industrial microorganisms.

PubMed

Papini, Marta; Salazar, Margarita; Nielsen, Jens

2010-01-01

The field of industrial biotechnology is expanding rapidly as the chemical industry is looking towards more sustainable production of chemicals that can be used as fuels or building blocks for production of solvents and materials. In connection with the development of sustainable bioprocesses, it is a major challenge to design and develop efficient cell factories that can ensure cost efficient conversion of the raw material into the chemical of interest. This is achieved through metabolic engineering, where the metabolism of the cell factory is engineered such that there is an efficient conversion of sugars, the typical raw materials in the fermentation industry, into the desired product. However, engineering of cellular metabolism is often challenging due to the complex regulation that has evolved in connection with adaptation of the different microorganisms to their ecological niches. In order to map these regulatory structures and further de-regulate them, as well as identify ingenious metabolic engineering strategies that full-fill mass balance constraints, tools from systems biology can be applied. This involves both high-throughput analysis tools like transcriptome, proteome and metabolome analysis, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies. It is in fact expected that systems biology may substantially improve the process of cell factory development, and we therefore propose the term Industrial Systems Biology for how systems biology will enhance the development of industrial biotechnology for sustainable chemical production.

Wireless Biological Electronic Sensors

PubMed Central

Cui, Yue

2017-01-01

The development of wireless biological electronic sensors could open up significant advances for both fundamental studies and practical applications in a variety of areas, including medical diagnosis, environmental monitoring, and defense applications. One of the major challenges in the development of wireless bioelectronic sensors is the successful integration of biosensing units and wireless signal transducers. In recent years, there are a few types of wireless communication systems that have been integrated with biosensing systems to construct wireless bioelectronic sensors. To successfully construct wireless biological electronic sensors, there are several interesting questions: What types of biosensing transducers can be used in wireless bioelectronic sensors? What types of wireless systems can be integrated with biosensing transducers to construct wireless bioelectronic sensors? How are the electrical sensing signals generated and transmitted? This review will highlight the early attempts to address these questions in the development of wireless biological electronic sensors. PMID:28991220

Engineering biological systems using automated biofoundries

PubMed Central

Chao, Ran; Mishra, Shekhar; Si, Tong; Zhao, Huimin

2017-01-01

Engineered biological systems such as genetic circuits and microbial cell factories have promised to solve many challenges in the modern society. However, the artisanal processes of research and development are slow, expensive, and inconsistent, representing a major obstacle in biotechnology and bioengineering. In recent years, biological foundries or biofoundries have been developed to automate design-build-test engineering cycles in an effort to accelerate these processes. This review summarizes the enabling technologies for such biofoundries as well as their early successes and remaining challenges. PMID:28602523

Enterobacter aerogenes Needle Stick Leads to Improved Biological Management System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johanson, Richard E.

2004-08-01

A laboratory worker who received a needle stick from a contaminated needle while working with a culture containing Enterobactor aerogenes developed a laboratory acquired infection. Although this organism has been shown to cause community and nosocomial infections, there have been no documented cases of a laboratory acquired infections. Lessons learned from the event led to corrective actions which included modification of lab procedures, development of a biological inventory tracking and risk identification system and the establishment of an effective biological safety program.

Review of S100A9 Biology and its Role in Cancer

PubMed Central

Markowitz, Joseph; Carson, William E.

2013-01-01

S100A9 is a calcium binding protein with multiple ligands and post-translation modifications that is involved in inflammatory events and the initial development of the cancer cell through to the development of metastatic disease. This review has a threefold purpose: 1) describe S100A9 structural elements important for its biological activity, 2) describe S100A9 biology in the context of the immune system, and 3) illustrate the role of S100A9 in the development of malignancy via interactions with the immune system and other cellular processes. PMID:23123827

Analyzing Change in Students' Gene-to-Evolution Models in College-Level Introductory Biology

ERIC Educational Resources Information Center

Dauer, Joseph T.; Momsen, Jennifer L.; Speth, Elena Bray; Makohon-Moore, Sasha C.; Long, Tammy M.

2013-01-01

Research in contemporary biology has become increasingly complex and organized around understanding biological processes in the context of systems. To better reflect the ways of thinking required for learning about systems, we developed and implemented a pedagogical approach using box-and-arrow models (similar to concept maps) as a foundational…

Graphics processing units in bioinformatics, computational biology and systems biology.

PubMed

Nobile, Marco S; Cazzaniga, Paolo; Tangherloni, Andrea; Besozzi, Daniela

2017-09-01

Several studies in Bioinformatics, Computational Biology and Systems Biology rely on the definition of physico-chemical or mathematical models of biological systems at different scales and levels of complexity, ranging from the interaction of atoms in single molecules up to genome-wide interaction networks. Traditional computational methods and software tools developed in these research fields share a common trait: they can be computationally demanding on Central Processing Units (CPUs), therefore limiting their applicability in many circumstances. To overcome this issue, general-purpose Graphics Processing Units (GPUs) are gaining an increasing attention by the scientific community, as they can considerably reduce the running time required by standard CPU-based software, and allow more intensive investigations of biological systems. In this review, we present a collection of GPU tools recently developed to perform computational analyses in life science disciplines, emphasizing the advantages and the drawbacks in the use of these parallel architectures. The complete list of GPU-powered tools here reviewed is available at http://bit.ly/gputools. © The Author 2016. Published by Oxford University Press.

Synthetic biology: applying biological circuits beyond novel therapies.

PubMed

Dobrin, Anton; Saxena, Pratik; Fussenegger, Martin

2016-04-18

Synthetic biology, an engineering, circuit-driven approach to biology, has developed whole new classes of therapeutics. Unfortunately, these advances have thus far been undercapitalized upon by basic researchers. As discussed herein, using synthetic circuits, one can undertake exhaustive investigations of the endogenous circuitry found in nature, develop novel detectors and better temporally and spatially controlled inducers. One could detect changes in DNA, RNA, protein or even transient signaling events, in cell-based systems, in live mice, and in humans. Synthetic biology has also developed inducible systems that can be induced chemically, optically or using radio waves. This induction has been re-wired to lead to changes in gene expression, RNA stability and splicing, protein stability and splicing, and signaling via endogenous pathways. Beyond simple detectors and inducible systems, one can combine these modalities and develop novel signal integration circuits that can react to a very precise pre-programmed set of conditions or even to multiple sets of precise conditions. In this review, we highlight some tools that were developed in which these circuits were combined such that the detection of a particular event automatically triggered a specific output. Furthermore, using novel circuit-design strategies, circuits have been developed that can integrate multiple inputs together in Boolean logic gates composed of up to 6 inputs. We highlight the tools available and what has been developed thus far, and highlight how some clinical tools can be very useful in basic science. Most of the systems that are presented can be integrated together; and the possibilities far exceed the number of currently developed strategies.

Potentials of single-cell biology in identification and validation of disease biomarkers.

PubMed

Niu, Furong; Wang, Diane C; Lu, Jiapei; Wu, Wei; Wang, Xiangdong

2016-09-01

Single-cell biology is considered a new approach to identify and validate disease-specific biomarkers. However, the concern raised by clinicians is how to apply single-cell measurements for clinical practice, translate the message of single-cell systems biology into clinical phenotype or explain alterations of single-cell gene sequencing and function in patient response to therapies. This study is to address the importance and necessity of single-cell gene sequencing in the identification and development of disease-specific biomarkers, the definition and significance of single-cell biology and single-cell systems biology in the understanding of single-cell full picture, the development and establishment of whole-cell models in the validation of targeted biological function and the figure and meaning of single-molecule imaging in single cell to trace intra-single-cell molecule expression, signal, interaction and location. We headline the important role of single-cell biology in the discovery and development of disease-specific biomarkers with a special emphasis on understanding single-cell biological functions, e.g. mechanical phenotypes, single-cell biology, heterogeneity and organization of genome function. We have reason to believe that such multi-dimensional, multi-layer, multi-crossing and stereoscopic single-cell biology definitely benefits the discovery and development of disease-specific biomarkers. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Electromagnetic fields as structure-function zeitgebers in biological systems: environmental orchestrations of morphogenesis and consciousness.

PubMed

Rouleau, Nicolas; Dotta, Blake T

2014-01-01

Within a cell system structure dictates function. Any interaction between cells, or a cell and its environment, has the potential to have long term implications on the function of a given cell and emerging cell aggregates. The structure and function of cells are continuously subjected to modification by electrical and chemical stimuli. However, biological systems are also subjected to an ever-present influence: the electromagnetic (EM) environment. Biological systems have the potential to be influenced by subtle energies which are exchanged at atomic and subatomic scales as EM phenomena. These energy exchanges have the potential to manifest at higher orders of discourse and affect the output (behavior) of a biological system. Here we describe theoretical and experimental evidence of EM influence on cells and the integration of whole systems. Even weak interactions between EM energies and biological systems display the potential to affect a developing system. We suggest the growing literature of EM effects on biological systems has significant implications to the cell and its functional aggregates.

Biophysics and systems biology.

PubMed

Noble, Denis

2010-03-13

Biophysics at the systems level, as distinct from molecular biophysics, acquired its most famous paradigm in the work of Hodgkin and Huxley, who integrated their equations for the nerve impulse in 1952. Their approach has since been extended to other organs of the body, notably including the heart. The modern field of computational biology has expanded rapidly during the first decade of the twenty-first century and, through its contribution to what is now called systems biology, it is set to revise many of the fundamental principles of biology, including the relations between genotypes and phenotypes. Evolutionary theory, in particular, will require re-assessment. To succeed in this, computational and systems biology will need to develop the theoretical framework required to deal with multilevel interactions. While computational power is necessary, and is forthcoming, it is not sufficient. We will also require mathematical insight, perhaps of a nature we have not yet identified. This article is therefore also a challenge to mathematicians to develop such insights.

Biophysics and systems biology

PubMed Central

Noble, Denis

2010-01-01

Biophysics at the systems level, as distinct from molecular biophysics, acquired its most famous paradigm in the work of Hodgkin and Huxley, who integrated their equations for the nerve impulse in 1952. Their approach has since been extended to other organs of the body, notably including the heart. The modern field of computational biology has expanded rapidly during the first decade of the twenty-first century and, through its contribution to what is now called systems biology, it is set to revise many of the fundamental principles of biology, including the relations between genotypes and phenotypes. Evolutionary theory, in particular, will require re-assessment. To succeed in this, computational and systems biology will need to develop the theoretical framework required to deal with multilevel interactions. While computational power is necessary, and is forthcoming, it is not sufficient. We will also require mathematical insight, perhaps of a nature we have not yet identified. This article is therefore also a challenge to mathematicians to develop such insights. PMID:20123750

6th Institute for Systems Biology International Symposium: Systems Biology and the Environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galitski, Timothy P.

2007-04-23

Systems biology recognizes the complex multi-scale organization of biological systems, from molecules to ecosystems. The International Symposium on Systems Biology is an annual two-day event gathering the most influential researchers transforming biology into an integrative discipline investigating complex systems. In recognition of the fundamental similarity between the scientific problems addressed in environmental science and systems biology studies at the molecular, cellular, and organismal levels, the 2007 Symposium featured global leaders in “Systems Biology and the Environment.” The objective of the 2007 “Systems Biology and the Environment” International Symposium was to stimulate interdisciplinary thinking and research that spans systems biology andmore » environmental science. This Symposium was well aligned with the DOE’s Genomics: GTL program efforts to achieve scientific objectives for each of the three DOE missions: Develop biofuels as a major secure energy source for this century; Develop biological solutions for intractable environmental problems; Understand biosystems’ climate impacts and assess sequestration strategies. Our scientific program highlighted world-class research exemplifying these priorities. The Symposium featured 45 minute lectures from 12 researchers including: Penny/Sallie Chisholm of MIT gave the keynote address “Tiny Cells, Global Impact: What Prochlorococcus Can Teach Us About Systems Biology”, plus Jim Fredrickson of PNNL, Nitin Baliga of ISB, Steve Briggs of UCSD, David Cox of Perlegen Sciences, Antoine Danchin of Institut Pasteur, John Delaney of the U of Washington, John Groopman of Johns Hopkins, Ben Kerr of the U of Washington, Steve Koonin of BP, Elliott Meyerowitz of Caltech, and Ed Rubin of LBNL. The 2007 Symposium promoted DOE’s three mission areas among scientists from multiple disciplines representing academia, non-profit research institutions, and the private sector. As in all previous Symposia, we had excellent attendance of participants representing 20-30 academic or research-oriented facilities along with 25-30 private corporations from 5-10 countries. To broaden the audience for the Symposium and ensure the continued accessibility of the presentations, we made the presentation videos available afterward on the ISB’s website.« less

Microscopic video observation of capillary vessel systems using diffuse back lighting

NASA Astrophysics Data System (ADS)

Sakai, Minako; Arai, Hiroki; Iwai, Toshiaki

2017-04-01

We have been developing a simple and practical video microscopy system based on absorption spectra of biological substance to perform spectroscopic observation of living tissues. The diffuse backlighting effect is actively used in the developed system, which is generated by multiple light scattering in the tissue. It is demonstrated that the light specularly reflected from the skin surface can be completely suppressed in the microscopic observation and the biological activity of the capillary vessel systems distributed under the skin can be successfully observed. As a result, we can confirm the effectiveness of the video microscopy system using diffuse backlighting and the applicability of our developed system.

Directed evolution and synthetic biology applications to microbial systems.

PubMed

Bassalo, Marcelo C; Liu, Rongming; Gill, Ryan T

2016-06-01

Biotechnology applications require engineering complex multi-genic traits. The lack of knowledge on the genetic basis of complex phenotypes restricts our ability to rationally engineer them. However, complex phenotypes can be engineered at the systems level, utilizing directed evolution strategies that drive whole biological systems toward desired phenotypes without requiring prior knowledge of the genetic basis of the targeted trait. Recent developments in the synthetic biology field accelerates the directed evolution cycle, facilitating engineering of increasingly complex traits in biological systems. In this review, we summarize some of the most recent advances in directed evolution and synthetic biology that allows engineering of complex traits in microbial systems. Then, we discuss applications that can be achieved through engineering at the systems level. Copyright © 2016 Elsevier Ltd. All rights reserved.

Extracting biomarkers of commitment to cancer development: potential role of vibrational spectroscopy in systems biology.

PubMed

Theophilou, Georgios; Paraskevaidi, Maria; Lima, Kássio M G; Kyrgiou, Maria; Martin-Hirsch, Pierre L; Martin, Francis L

2015-05-01

The complex processes driving cancer have so far impeded the discovery of dichotomous biomarkers associated with its initiation and progression. Reductionist approaches utilizing 'omics' technologies have met some success in identifying molecular alterations associated with carcinogenesis. Systems biology is an emerging science that combines high-throughput investigation techniques to define the dynamic interplay between regulatory biological systems in response to internal and external cues. Vibrational spectroscopy has the potential to play an integral role within systems biology research approaches. It is capable of examining global models of carcinogenesis by scrutinizing chemical bond alterations within molecules. The application of infrared or Raman spectroscopic approaches coupled with computational analysis under the systems biology umbrella can assist the transition of biomarker research from the molecular level to the system level. The comprehensive representation of carcinogenesis as a multilevel biological process will inevitably revolutionize cancer-related healthcare by personalizing risk prediction and prevention.

Interactive Biology[TM] Multimedia Courseware Series. [CD-ROM].

ERIC Educational Resources Information Center

1999

Interactive Biology Multimedia Courseware is an on-going project, with new titles continually under development. Currently, Interactive Biology includes 38 biological titles on CD-ROM for Macintosh and IBM-compatible systems. Each title deals with a specific biological subject and provides in-depth, comprehensive course material for the 9th grade…

Cancer Systems Biology: a peak into the future of patient care?

PubMed Central

Werner, Henrica M. J.; Mills, Gordon B.; Ram, Prahlad T.

2015-01-01

Traditionally, scientific research has focused on studying individual events, such as single mutations, gene function or the effect of the manipulation of one protein on a biological phenotype. A range of technologies, combined with the ability to develop robust and predictive mathematical models, is beginning to provide information that will enable a holistic view of how the genomic and epigenetic aberrations in cancer cells can alter the homeostasis of signalling networks within these cells, between cancer cells and the local microenvironment, at the organ and organism level. This systems biology process needs to be integrated with an iterative approach wherein hypotheses and predictions that arise from modelling are refined and constrained by experimental evaluation. Systems biology approaches will be vital for developing and implementing effective strategies to deliver personalized cancer therapy. Specifically, these approaches will be important to select those patients most likely to benefit from targeted therapies as well as for the development and implementation of rational combinatorial therapies. Systems biology can help to increase therapy efficacy or bypass the emergence of resistance, thus converting the current (often short term) effects of targeted therapies into durable responses, ultimately to improve quality of life and provide a cure. PMID:24492837

Detecting Motion from a Moving Platform; Phase 3: Unification of Control and Sensing for More Advanced Situational Awareness

DTIC Science & Technology

2011-11-01

RX-TY-TR-2011-0096-01) develops a novel computer vision sensor based upon the biological vision system of the common housefly , Musca domestica...01 summarizes the development of a novel computer vision sensor based upon the biological vision system of the common housefly , Musca domestica

Systems biology approach to developing S(2)RM-based "systems therapeutics" and naturally induced pluripotent stem cells.

PubMed

Maguire, Greg; Friedman, Peter

2015-05-26

The degree to, and the mechanisms through, which stem cells are able to build, maintain, and heal the body have only recently begun to be understood. Much of the stem cell's power resides in the release of a multitude of molecules, called stem cell released molecules (SRM). A fundamentally new type of therapeutic, namely "systems therapeutic", can be realized by reverse engineering the mechanisms of the SRM processes. Recent data demonstrates that the composition of the SRM is different for each type of stem cell, as well as for different states of each cell type. Although systems biology has been successfully used to analyze multiple pathways, the approach is often used to develop a small molecule interacting at only one pathway in the system. A new model is emerging in biology where systems biology is used to develop a new technology acting at multiple pathways called "systems therapeutics". A natural set of healing pathways in the human that uses SRM is instructive and of practical use in developing systems therapeutics. Endogenous SRM processes in the human body use a combination of SRM from two or more stem cell types, designated as S(2)RM, doing so under various state dependent conditions for each cell type. Here we describe our approach in using state-dependent SRM from two or more stem cell types, S(2)RM technology, to develop a new class of therapeutics called "systems therapeutics." Given the ubiquitous and powerful nature of innate S(2)RM-based healing in the human body, this "systems therapeutic" approach using S(2)RM technology will be important for the development of anti-cancer therapeutics, antimicrobials, wound care products and procedures, and a number of other therapeutics for many indications.

Recent Progress in the Development of Metabolome Databases for Plant Systems Biology

PubMed Central

Fukushima, Atsushi; Kusano, Miyako

2013-01-01

Metabolomics has grown greatly as a functional genomics tool, and has become an invaluable diagnostic tool for biochemical phenotyping of biological systems. Over the past decades, a number of databases involving information related to mass spectra, compound names and structures, statistical/mathematical models and metabolic pathways, and metabolite profile data have been developed. Such databases complement each other and support efficient growth in this area, although the data resources remain scattered across the World Wide Web. Here, we review available metabolome databases and summarize the present status of development of related tools, particularly focusing on the plant metabolome. Data sharing discussed here will pave way for the robust interpretation of metabolomic data and advances in plant systems biology. PMID:23577015

Controllability and observability of Boolean networks arising from biology

NASA Astrophysics Data System (ADS)

Li, Rui; Yang, Meng; Chu, Tianguang

2015-02-01

Boolean networks are currently receiving considerable attention as a computational scheme for system level analysis and modeling of biological systems. Studying control-related problems in Boolean networks may reveal new insights into the intrinsic control in complex biological systems and enable us to develop strategies for manipulating biological systems using exogenous inputs. This paper considers controllability and observability of Boolean biological networks. We propose a new approach, which draws from the rich theory of symbolic computation, to solve the problems. Consequently, simple necessary and sufficient conditions for reachability, controllability, and observability are obtained, and algorithmic tests for controllability and observability which are based on the Gröbner basis method are presented. As practical applications, we apply the proposed approach to several different biological systems, namely, the mammalian cell-cycle network, the T-cell activation network, the large granular lymphocyte survival signaling network, and the Drosophila segment polarity network, gaining novel insights into the control and/or monitoring of the specific biological systems.

Perspective: Reaches of chemical physics in biology.

PubMed

Gruebele, Martin; Thirumalai, D

2013-09-28

Chemical physics as a discipline contributes many experimental tools, algorithms, and fundamental theoretical models that can be applied to biological problems. This is especially true now as the molecular level and the systems level descriptions begin to connect, and multi-scale approaches are being developed to solve cutting edge problems in biology. In some cases, the concepts and tools got their start in non-biological fields, and migrated over, such as the idea of glassy landscapes, fluorescence spectroscopy, or master equation approaches. In other cases, the tools were specifically developed with biological physics applications in mind, such as modeling of single molecule trajectories or super-resolution laser techniques. In this introduction to the special topic section on chemical physics of biological systems, we consider a wide range of contributions, all the way from the molecular level, to molecular assemblies, chemical physics of the cell, and finally systems-level approaches, based on the contributions to this special issue. Chemical physicists can look forward to an exciting future where computational tools, analytical models, and new instrumentation will push the boundaries of biological inquiry.

Perspective: Reaches of chemical physics in biology

PubMed Central

Gruebele, Martin; Thirumalai, D.

2013-01-01

Chemical physics as a discipline contributes many experimental tools, algorithms, and fundamental theoretical models that can be applied to biological problems. This is especially true now as the molecular level and the systems level descriptions begin to connect, and multi-scale approaches are being developed to solve cutting edge problems in biology. In some cases, the concepts and tools got their start in non-biological fields, and migrated over, such as the idea of glassy landscapes, fluorescence spectroscopy, or master equation approaches. In other cases, the tools were specifically developed with biological physics applications in mind, such as modeling of single molecule trajectories or super-resolution laser techniques. In this introduction to the special topic section on chemical physics of biological systems, we consider a wide range of contributions, all the way from the molecular level, to molecular assemblies, chemical physics of the cell, and finally systems-level approaches, based on the contributions to this special issue. Chemical physicists can look forward to an exciting future where computational tools, analytical models, and new instrumentation will push the boundaries of biological inquiry. PMID:24089712

The use of 'Omics technology to rationally improve industrial mammalian cell line performance.

PubMed

Lewis, Amanda M; Abu-Absi, Nicholas R; Borys, Michael C; Li, Zheng Jian

2016-01-01

Biologics represent an increasingly important class of therapeutics, with 7 of the 10 top selling drugs from 2013 being in this class. Furthermore, health authority approval of biologics in the immuno-oncology space is expected to transform treatment of patients with debilitating and deadly diseases. The growing importance of biologics in the healthcare field has also resulted in the recent approvals of several biosimilars. These recent developments, combined with pressure to provide treatments at lower costs to payers, are resulting in increasing need for the industry to quickly and efficiently develop high yielding, robust processes for the manufacture of biologics with the ability to control quality attributes within narrow distributions. Achieving this level of manufacturing efficiency and the ability to design processes capable of regulating growth, death and other cellular pathways through manipulation of media, feeding strategies, and other process parameters will undoubtedly be facilitated through systems biology tools generated in academic and public research communities. Here we discuss the intersection of systems biology, 'Omics technologies, and mammalian bioprocess sciences. Specifically, we address how these methods in conjunction with traditional monitoring techniques represent a unique opportunity to better characterize and understand host cell culture state, shift from an empirical to rational approach to process development and optimization of bioreactor cultivation processes. We summarize the following six key areas: (i) research applied to parental, non-recombinant cell lines; (ii) systems level datasets generated with recombinant cell lines; (iii) datasets linking phenotypic traits to relevant biomarkers; (iv) data depositories and bioinformatics tools; (v) in silico model development, and (vi) examples where these approaches have been used to rationally improve cellular processes. We critically assess relevant and state of the art research being conducted in academic, government and industrial laboratories. Furthermore, we apply our expertise in bioprocess to define a potential model for integration of these systems biology approaches into biologics development. © 2015 Wiley Periodicals, Inc.

78 FR 22527 - Army Science Board Request for Information on Technology and Core Competencies

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-16

...); Edgewood Chemical Biological Command (ECBC); Natick Soldier Research, Development & Engineering Center...; C4ISR; Night Vision; Chemical/Biological Warfare; and Soldier Systems. The study will focus on...); Armament Research, Development & Engineering Center (ARDEC); Aviation & Missile Research, Development...

Proceedings of the workshop "Development of biological decision support systems for resource managers": Denver, Colorado, October 27-29, 1998

USGS Publications Warehouse

Getter, James; D'Erchia, Terry D.; Root, Ralph; Getter, James; D'Erchia, Terry D.; Root, Ralph

1999-01-01

The format for this 3-day workshop (27-29 October 1998) included plenary presentations by USGS Biological Resources Division (BRD) and U.S. Fish and Wildlife Service per onnel who u e and develop decision support systems (DSS); breakout ses ions addressing DSS technical information aspect , outreach/ customer requirements, and future perspectives; and a DSS Steering Committee meeting to evaluate work hop goals and to provide guidance for fu ture efforts. Steering committee action item developed from workshop inputs were to ( I) develop a "DSS framework" document for u e in biological research. (2) develop a "proof of concept" DSS based upon the framework document, and (3) integrate decision support ystem into BRD program elements.

To Fly or Not to Fly: Teaching Advanced Secondary School Students about Principles of Flight in Biological Systems

ERIC Educational Resources Information Center

Pietsch, Renée B.; Bohland, Cynthia L.; Schmale, David G., III.

2015-01-01

Biological flight mechanics is typically taught in graduate level college classes rather than in secondary school classes. We developed an interdisciplinary unit for advanced upper-level secondary school students (ages 15-18) to teach the principles of flight and applications to biological systems. This unit capitalised on the tremendous…

Thinking about Digestive System in Early Childhood: A Comparative Study about Biological Knowledge

ERIC Educational Resources Information Center

AHI, Berat

2017-01-01

The current study aims to explore how children explain the concepts of biology and how biological knowledge develops across ages by focusing on the structure and functions of the digestive system. The study was conducted with 60 children. The data were collected through the interviews conducted within a think-aloud protocol. The interview data…

Systems Medicine: Sketching the Landscape.

PubMed

Kirschner, Marc

2016-01-01

To understand the meaning of the term Systems Medicine and to distinguish it from seemingly related other expressions currently in use, such as precision, personalized, -omics, or big data medicine, its underlying history and development into present time needs to be highlighted. Having this development in mind, it becomes evident that Systems Medicine is a genuine concept as well as a novel way of tackling the manifold complexity that occurs in nowadays clinical medicine-and not just a rebranding of what has previously been done in the past. So looking back it seems clear to many in the field that Systems Medicine has its origin in an integrative method to unravel biocomplexity, namely, Systems Biology. Here scientist by now gained useful experience that is on the verge toward implementation in clinical research and practice.Systems Medicine and Systems Biology have the same underlying theoretical principle in systems-based thinking-a methodology to understand complexity that can be traced back to ancient Greece. During the last decade, however, and due to a rapid methodological development in the life sciences and computing/IT technologies, Systems Biology has evolved from a scientific concept into an independent discipline most competent to tackle key questions of biocomplexity-with the potential to transform medicine and how it will be practiced in the future. To understand this process in more detail, the following section will thus give a short summary of the foundation of systems-based thinking and the different developmental stages including systems theory, the development of modern Systems Biology, and its transition into clinical practice. These are the components to pave the way toward Systems Medicine.

Mammalian synthetic biology for studying the cell

PubMed Central

Mathur, Melina; Xiang, Joy S.

2017-01-01

Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. PMID:27932576

Measurement of 100 B. anthracis Ames spores within 15 minutes by SERS at the US Army Edgewood Chemical Biological Ctr.

NASA Astrophysics Data System (ADS)

Farquharson, Stuart; Shende, Chetan; Smith, Wayne; Huang, Hermes; Sperry, Jay; Sickler, Todd; Prugh, Amber; Guicheteau, Jason

2014-05-01

Since the distribution of Bacillus anthracis-Ames spores through the US Postal System, there has been a persistent fear that biological warfare agents will be used by terrorists against our military abroad and our civilians at home. While there has been substantial effort since the anthrax attack of 2001 to develop analyzers to detect this and other biological warfare agents, the analyzers remain either too slow, lack sensitivity, produce high false-positive rates, or cannot be fielded. In an effort to overcome these limitations we have been developing a surface-enhanced Raman spectroscopy system. Here we describe the use of silver nanoparticles functionalized with a short peptide to selectively capture Bacillus anthracis spores and produce SER scattering. Specifically, measurements of 100 B. anthracis-Ames spores/mL in ~25 minutes performed at the US Army's Edgewood Chemical Biological Center are presented. The measurements provide a basis for the development of systems that can detect spores collected from the air or water supplies with the potential of saving lives during a biological warfare attack.

Plant MetGenMAP: an integrative analysis system for plant systems biology

USDA-ARS?s Scientific Manuscript database

We have developed a web-based system, Plant MetGenMAP, which can identify significantly altered biochemical pathways and highly affected biological processes, predict functional roles of pathway genes, and potential pathway-related regulatory motifs from transcript and metabolite profile datasets. P...

Biological Basis For Computer Vision: Some Perspectives

NASA Astrophysics Data System (ADS)

Gupta, Madan M.

1990-03-01

Using biology as a basis for the development of sensors, devices and computer vision systems is a challenge to systems and vision scientists. It is also a field of promising research for engineering applications. Biological sensory systems, such as vision, touch and hearing, sense different physical phenomena from our environment, yet they possess some common mathematical functions. These mathematical functions are cast into the neural layers which are distributed throughout our sensory regions, sensory information transmission channels and in the cortex, the centre of perception. In this paper, we are concerned with the study of the biological vision system and the emulation of some of its mathematical functions, both retinal and visual cortex, for the development of a robust computer vision system. This field of research is not only intriguing, but offers a great challenge to systems scientists in the development of functional algorithms. These functional algorithms can be generalized for further studies in such fields as signal processing, control systems and image processing. Our studies are heavily dependent on the the use of fuzzy - neural layers and generalized receptive fields. Building blocks of such neural layers and receptive fields may lead to the design of better sensors and better computer vision systems. It is hoped that these studies will lead to the development of better artificial vision systems with various applications to vision prosthesis for the blind, robotic vision, medical imaging, medical sensors, industrial automation, remote sensing, space stations and ocean exploration.

Quantitative biology of single neurons

PubMed Central

Eberwine, James; Lovatt, Ditte; Buckley, Peter; Dueck, Hannah; Francis, Chantal; Kim, Tae Kyung; Lee, Jaehee; Lee, Miler; Miyashiro, Kevin; Morris, Jacqueline; Peritz, Tiina; Schochet, Terri; Spaethling, Jennifer; Sul, Jai-Yoon; Kim, Junhyong

2012-01-01

The building blocks of complex biological systems are single cells. Fundamental insights gained from single-cell analysis promise to provide the framework for understanding normal biological systems development as well as the limits on systems/cellular ability to respond to disease. The interplay of cells to create functional systems is not well understood. Until recently, the study of single cells has concentrated primarily on morphological and physiological characterization. With the application of new highly sensitive molecular and genomic technologies, the quantitative biochemistry of single cells is now accessible. PMID:22915636

Macro- and microscale fluid flow systems for endothelial cell biology.

PubMed

Young, Edmond W K; Simmons, Craig A

2010-01-21

Recent advances in microfluidics have brought forth new tools for studying flow-induced effects on mammalian cells, with important applications in cardiovascular, bone and cancer biology. The plethora of microscale systems developed to date demonstrate the flexibility of microfluidic designs, and showcase advantages of the microscale that are simply not available at the macroscale. However, the majority of these systems will likely not achieve widespread use in the biological laboratory due to their complexity and lack of user-friendliness. To gain widespread acceptance in the biological research community, microfluidics engineers must understand the needs of cell biologists, while biologists must be made aware of available technology. This review provides a critical evaluation of cell culture flow (CCF) systems used to study the effects of mechanical forces on endothelial cells (ECs) in vitro. To help understand the need for various designs of CCF systems, we first briefly summarize main properties of ECs and their native environments. Basic principles of various macro- and microscale systems are described and evaluated. New opportunities are uncovered for developing technologies that have potential to both improve efficiency of experimentation as well as answer important biological questions that otherwise cannot be tackled with existing systems. Finally, we discuss some of the unresolved issues related to microfluidic cell culture, suggest possible avenues of investigation that could resolve these issues, and provide an outlook for the future of microfluidics in biological research.

Promoting microbiology education through the iGEM synthetic biology competition.

PubMed

Kelwick, Richard; Bowater, Laura; Yeoman, Kay H; Bowater, Richard P

2015-08-01

Synthetic biology has developed rapidly in the 21st century. It covers a range of scientific disciplines that incorporate principles from engineering to take advantage of and improve biological systems, often applied to specific problems. Methods important in this subject area include the systematic design and testing of biological systems and, here, we describe how synthetic biology projects frequently develop microbiology skills and education. Synthetic biology research has huge potential in biotechnology and medicine, which brings important ethical and moral issues to address, offering learning opportunities about the wider impact of microbiological research. Synthetic biology projects have developed into wide-ranging training and educational experiences through iGEM, the International Genetically Engineered Machines competition. Elements of the competition are judged against specific criteria and teams can win medals and prizes across several categories. Collaboration is an important element of iGEM, and all DNA constructs synthesized by iGEM teams are made available to all researchers through the Registry for Standard Biological Parts. An overview of microbiological developments in the iGEM competition is provided. This review is targeted at educators that focus on microbiology and synthetic biology, but will also be of value to undergraduate and postgraduate students with an interest in this exciting subject area. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Systems-Level Analysis of Innate Immunity

PubMed Central

Zak, Daniel E.; Tam, Vincent C.; Aderem, Alan

2014-01-01

Systems-level analysis of biological processes strives to comprehensively and quantitatively evaluate the interactions between the relevant molecular components over time, thereby enabling development of models that can be employed to ultimately predict behavior. Rapid development in measurement technologies (omics), when combined with the accessible nature of the cellular constituents themselves, is allowing the field of innate immunity to take significant strides toward this lofty goal. In this review, we survey exciting results derived from systems biology analyses of the immune system, ranging from gene regulatory networks to influenza pathogenesis and systems vaccinology. PMID:24655298

Connections Matter: Social Networks and Lifespan Health in Primate Translational Models

PubMed Central

McCowan, Brenda; Beisner, Brianne; Bliss-Moreau, Eliza; Vandeleest, Jessica; Jin, Jian; Hannibal, Darcy; Hsieh, Fushing

2016-01-01

Humans live in societies full of rich and complex relationships that influence health. The ability to improve human health requires a detailed understanding of the complex interplay of biological systems that contribute to disease processes, including the mechanisms underlying the influence of social contexts on these biological systems. A longitudinal computational systems science approach provides methods uniquely suited to elucidate the mechanisms by which social systems influence health and well-being by investigating how they modulate the interplay among biological systems across the lifespan. In the present report, we argue that nonhuman primate social systems are sufficiently complex to serve as model systems allowing for the development and refinement of both analytical and theoretical frameworks linking social life to health. Ultimately, developing systems science frameworks in nonhuman primate models will speed discovery of the mechanisms that subserve the relationship between social life and human health. PMID:27148103

Systems Vaccinology: Enabling rational vaccine design with systems biological approaches

PubMed Central

Hagan, Thomas; Nakaya, Helder I.; Subramaniam, Shankar; Pulendran, Bali

2015-01-01

Vaccines have drastically reduced the mortality and morbidity of many diseases. However, vaccines have historically been developed empirically, and recent development of vaccines against current pandemics such as HIV and malaria has been met with difficulty. The advent of high-throughput technologies, coupled with systems biological methods of data analysis, has enabled researchers to interrogate the entire complement of a variety of molecular components within cells, and characterize the myriad interactions among them in order to model and understand the behavior of the system as a whole. In the context of vaccinology, these tools permit exploration of the molecular mechanisms by which vaccines induce protective immune responses. Here we review the recent advances, challenges, and potential of systems biological approaches in vaccinology. If the challenges facing this developing field can be overcome, systems vaccinology promises to empower the identification of early predictive signatures of vaccine response, as well as novel and robust correlates of protection from infection. Such discoveries, along with the improved understanding of immune responses to vaccination they impart, will play an instrumental role in development of the next generation of rationally designed vaccines. PMID:25858860

Plant defense compounds: systems approaches to metabolic analysis.

PubMed

Kliebenstein, Daniel J

2012-01-01

Systems biology attempts to answer biological questions by integrating across diverse genomic data sets. With the increasing ability to conduct genomics experiments, this integrative approach is being rapidly applied across numerous biological research communities. One of these research communities investigates how plants utilize secondary metabolites or defense metabolites to defend against attack by pathogens and other biotic organisms. This use of systems biology to integrate across transcriptomics, metabolomics, and genomics is significantly enhancing the rate of discovery of genes, metabolites, and bioactivities for plant defense compounds as well as extending our knowledge of how these compounds are regulated. Plant defense compounds are also providing a unique proving platform to develop new approaches that enhance the ability to conduct systems biology with existing and previously unforseen genomics data sets. This review attempts to illustrate both how systems biology is helping the study of plant defense compounds and vice versa.

Priorities and developments of sensors, samplers and methods for key marine biological observations.

NASA Astrophysics Data System (ADS)

Simmons, Samantha; Chavez, Francisco; Pearlman, Jay

2016-04-01

Over the last two decades or more, physical oceanography has seen a significant growth in in-situ sensors and platforms including fixed point and cable observatories, Argo floats, gliders and AUVs to supplement satellites for creating a 3-D view of the time-varying global ocean temperature and salinity structures. There are important developments recently for biogeochemists for monitoring nitrate, chemical contaminants, oxygen and pH that can now be added to these autonomous systems. Biologists are still lagging. Given the importance of biology to ocean health and the future earth, and the present reliance on humans and ships for observing species and abundance, it is paramount that new biological sensor systems be developed. Some promising sensor systems based on, but not limited to acoustic, chemical, genomic or imaging techniques, can sense from microbes to whales, are on the horizon. These techniques can be applied in situ with either real time or recorded data and can be captured and returned to the laboratory using the autonomous systems. The number of samples is limiting, requiring adaptive and smart systems. Two steps are envisioned to meeting the challenges. The first is to identify the priority biological variables to focus observation requirements and planning. The second is to address new sensors that can fill the gaps in current capabilities for biological observations. This abstract will review recent efforts to identify core biological variables for the US Integrated Ocean Observing System and address new sensors and innovations for observing these variables, particularly focused on availability and maturity of sensors.

MCT-based SWIR hyperspectral imaging system for evaluation of biological samples

USDA-ARS?s Scientific Manuscript database

Hyperspectral imaging has been shown to be a powerful tool for nondestructive evaluation of biological samples. We recently developed a new line-scan-based shortwave infrared (SWIR) hyperspectral imaging system. Critical sensing components of the system include a SWIR spectrograph, an MCT (HgCdTe) a...

Towards systems metabolic engineering of microorganisms for amino acid production.

PubMed

Park, Jin Hwan; Lee, Sang Yup

2008-10-01

Microorganisms capable of efficient production of amino acids have traditionally been developed by random mutation and selection method, which might cause unwanted physiological changes in cellular metabolism. Rational genome-wide metabolic engineering based on systems and synthetic biology tools, which is termed 'systems metabolic engineering', is rising as an alternative to overcome these problems. Recently, several amino acid producers have been successfully developed by systems metabolic engineering, where the metabolic engineering procedures were performed within a systems biology framework, and entire metabolic networks, including complex regulatory circuits, were engineered in an integrated manner. Here we review the current status of systems metabolic engineering successfully applied for developing amino acid producing strains and discuss future prospects.

Synthetic biology: advancing the design of diverse genetic systems

PubMed Central

Wang, Yen-Hsiang; Wei, Kathy Y.; Smolke, Christina D.

2013-01-01

A main objective of synthetic biology is to make the process of designing genetically-encoded biological systems more systematic, predictable, robust, scalable, and efficient. The examples of genetic systems in the field vary widely in terms of operating hosts, compositional approaches, and network complexity, ranging from a simple genetic switch to search-and-destroy systems. While significant advances in synthesis capabilities support the potential for the implementation of pathway- and genome-scale programs, several design challenges currently restrict the scale of systems that can be reasonably designed and implemented. Synthetic biology offers much promise in developing systems to address challenges faced in manufacturing, the environment and sustainability, and health and medicine, but the realization of this potential is currently limited by the diversity of available parts and effective design frameworks. As researchers make progress in bridging this design gap, advances in the field hint at ever more diverse applications for biological systems. PMID:23413816

The NASA Space Radiobiology Risk Assessment Project

NASA Astrophysics Data System (ADS)

Cucinotta, Francis A.; Huff, Janice; Ponomarev, Artem; Patel, Zarana; Kim, Myung-Hee

The current first phase (2006-2011) has the three major goals of: 1) optimizing the conventional cancer risk models currently used based on the double-detriment life-table and radiation quality functions; 2) the integration of biophysical models of acute radiation syndromes; and 3) the development of new systems radiation biology models of cancer processes. The first-phase also includes continued uncertainty assessment of space radiation environmental models and transport codes, and relative biological effectiveness factors (RBE) based on flight data and NSRL results, respectively. The second phase of the (2012-2016) will: 1) develop biophysical models of central nervous system risks (CNS); 2) achieve comphrensive systems biology models of cancer processes using data from proton and heavy ion studies performed at NSRL; and 3) begin to identify computational models of biological countermeasures. Goals for the third phase (2017-2021) include: 1) the development of a systems biology model of cancer risks for operational use at NASA; 2) development of models of degenerative risks, 2) quantitative models of counter-measure impacts on cancer risks; and 3) indiviudal based risk assessments. Finally, we will support a decision point to continue NSRL research in support of NASA's exploration goals beyond 2021, and create an archival of NSRL research results for continued analysis. Details on near term goals, plans for a WEB based data resource of NSRL results, and a space radiation Wikepedia are described.

Bioprocess systems engineering: transferring traditional process engineering principles to industrial biotechnology.

PubMed

Koutinas, Michalis; Kiparissides, Alexandros; Pistikopoulos, Efstratios N; Mantalaris, Athanasios

2012-01-01

The complexity of the regulatory network and the interactions that occur in the intracellular environment of microorganisms highlight the importance in developing tractable mechanistic models of cellular functions and systematic approaches for modelling biological systems. To this end, the existing process systems engineering approaches can serve as a vehicle for understanding, integrating and designing biological systems and processes. Here, we review the application of a holistic approach for the development of mathematical models of biological systems, from the initial conception of the model to its final application in model-based control and optimisation. We also discuss the use of mechanistic models that account for gene regulation, in an attempt to advance the empirical expressions traditionally used to describe micro-organism growth kinetics, and we highlight current and future challenges in mathematical biology. The modelling research framework discussed herein could prove beneficial for the design of optimal bioprocesses, employing rational and feasible approaches towards the efficient production of chemicals and pharmaceuticals.

Bioprocess systems engineering: transferring traditional process engineering principles to industrial biotechnology

PubMed Central

Koutinas, Michalis; Kiparissides, Alexandros; Pistikopoulos, Efstratios N.; Mantalaris, Athanasios

2013-01-01

The complexity of the regulatory network and the interactions that occur in the intracellular environment of microorganisms highlight the importance in developing tractable mechanistic models of cellular functions and systematic approaches for modelling biological systems. To this end, the existing process systems engineering approaches can serve as a vehicle for understanding, integrating and designing biological systems and processes. Here, we review the application of a holistic approach for the development of mathematical models of biological systems, from the initial conception of the model to its final application in model-based control and optimisation. We also discuss the use of mechanistic models that account for gene regulation, in an attempt to advance the empirical expressions traditionally used to describe micro-organism growth kinetics, and we highlight current and future challenges in mathematical biology. The modelling research framework discussed herein could prove beneficial for the design of optimal bioprocesses, employing rational and feasible approaches towards the efficient production of chemicals and pharmaceuticals. PMID:24688682

Evolving Relevance of Neuroproteomics in Alzheimer's Disease.

PubMed

Lista, Simone; Zetterberg, Henrik; O'Bryant, Sid E; Blennow, Kaj; Hampel, Harald

2017-01-01

Substantial progress in the understanding of the biology of Alzheimer's disease (AD) has been achieved over the past decades. The early detection and diagnosis of AD and other age-related neurodegenerative diseases, however, remain a challenging scientific frontier. Therefore, the comprehensive discovery (relating to all individual, converging or diverging biochemical disease mechanisms), development, validation, and qualification of standardized biological markers with diagnostic and prognostic functions with a precise performance profile regarding specificity, sensitivity, and positive and negative predictive value are warranted.Methodological innovations in the area of exploratory high-throughput technologies, such as sequencing, microarrays, and mass spectrometry-based analyses of proteins/peptides, have led to the generation of large global molecular datasets from a multiplicity of biological systems, such as biological fluids, cells, tissues, and organs. Such methodological progress has shifted the attention to the execution of hypothesis-independent comprehensive exploratory analyses (opposed to the classical hypothesis-driven candidate approach), with the aim of fully understanding the biological systems in physiology and disease as a whole. The systems biology paradigm integrates experimental biology with accurate and rigorous computational modelling to describe and foresee the dynamic features of biological systems. The use of dynamically evolving technological platforms, including mass spectrometry, in the area of proteomics has enabled to rush the process of biomarker discovery and validation for refining significantly the diagnosis of AD. Currently, proteomics-which is part of the systems biology paradigm-is designated as one of the dominant matured sciences needed for the effective exploratory discovery of prospective biomarker candidates expected to play an effective role in aiding the early detection, diagnosis, prognosis, and therapy development in AD.

Organizing Community-Based Data Standards: Lessons from Developing a Successful Open Standard in Systems Biology

NASA Astrophysics Data System (ADS)

Hucka, M.

2015-09-01

In common with many fields, including astronomy, a vast number of software tools for computational modeling and simulation are available today in systems biology. This wealth of resources is a boon to researchers, but it also presents interoperability problems. Despite working with different software tools, researchers want to disseminate their work widely as well as reuse and extend the models of other researchers. This situation led in the year 2000 to an effort to create a tool-independent, machine-readable file format for representing models: SBML, the Systems Biology Markup Language. SBML has since become the de facto standard for its purpose. Its success and general approach has inspired and influenced other community-oriented standardization efforts in systems biology. Open standards are essential for the progress of science in all fields, but it is often difficult for academic researchers to organize successful community-based standards. I draw on personal experiences from the development of SBML and summarize some of the lessons learned, in the hope that this may be useful to other groups seeking to develop open standards in a community-oriented fashion.

Biophysics at the Boundaries: The Next Problem Sets

NASA Astrophysics Data System (ADS)

Skolnick, Malcolm

2009-03-01

The interface between physics and biology is one of the fastest growing subfields of physics. As knowledge of such topics as cellular processes and complex ecological systems advances, researchers have found that progress in understanding these and other systems requires application of more quantitative approaches. Today, there is a growing demand for quantitative and computational skills in biological research and the commercialization of that research. The fragmented teaching of science in our universities still leaves biology outside the quantitative and mathematical culture that is the foundation of physics. This is particularly inopportune at a time when the needs for quantitative thinking about biological systems are exploding. More physicists should be encouraged to become active in research and development in the growing application fields of biophysics including molecular genetics, biomedical imaging, tissue generation and regeneration, drug development, prosthetics, neural and brain function, kinetics of nonequilibrium open biological systems, metabolic networks, biological transport processes, large-scale biochemical networks and stochastic processes in biochemical systems to name a few. In addition to moving into basic research in these areas, there is increasing opportunity for physicists in industry beginning with entrepreneurial roles in taking research results out of the laboratory and in the industries who perfect and market the inventions and developments that physicists produce. In this talk we will identify and discuss emerging opportunities for physicists in biophysical and biotechnological pursuits ranging from basic research through development of applications and commercialization of results. This will include discussion of the roles of physicists in non-traditional areas apart from academia such as patent law, financial analysis and regulatory science and the problem sets assigned in education and training that will enable future biophysicists to fill these roles.

Improving Satellite Compatible Microdevices to Study Biology in Space

NASA Technical Reports Server (NTRS)

Kalkus, Trevor; Snyder, Jessica; Paulino-Lima, Ivan; Rothschild, Lynn

2017-01-01

The technology for biology in space lags far behind the gold standard for biological experiments on Earth. To remedy this disparity, the Rothschild lab works on proof of concept, prototyping, and developing of new sensors and devices to further the capabilities of biology research on satellites. One such device is the PowerCell Payload System. One goal for synthetic biology in aiding space travel and colonization is to genetically engineer living cells to produce biochemicals in space. However, such farming in space presupposes bacteria retain their functionality post-launch, bombarded by radiation, and without the 1G of Earth. Our questions is, does a co-culture of cyanobacteria and protein-synthesizing bacteria produce Earth-like yields of target proteins? Is the yield sensitive to variable gravitational forces? To answer these questions, a PowerCell Payload System will spend 1 year aboard the German Aerospace Center's Euglena and Combined Regenerative Organic-food Production In Space (Eu:CROPIS) mission satellite. The PowerCell system is a pair of two 48-well microfluidic cards, each well seeded with bacteria. The system integrates fluidic, thermal, optical, electronic, and control systems to germinate bacteria spores, then measure the protein synthesized for comparison to parallel experiments conducted on the Earth. In developing the PowerCell Payload, we gained insight into the shortcomings of biology experiments on satellites. To address these issues, we have started three new prototyping projects: 1) The development of an extremely stable and radiation resistant cell-free system, allowing for the construction of proteins utilizing only cell components instead of living cells. This can be lyophilized on a substrate, like paper. (2) Using paper as a microfluidic platform that is flexible, stable, cheap, and wicking. The capillary action eliminates the need for pumps, reducing volume, mass, and potential failing points. Electrodes can be printed on the paper to sense for biochemicals. (3) Developing a modular, semi-autonomous microfluidic device that can be easily adapted for a variety of common biological experiments. This versatility will allow for quicker and cheaper experimentation. These improvements to satellite experiment platforms have the potential to radically increase the return from NASA's biological and field studies with reduced development time, mass, and cost with increased robustness data and interpretation.

Mammalian synthetic biology for studying the cell.

PubMed

Mathur, Melina; Xiang, Joy S; Smolke, Christina D

2017-01-02

Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

Specifications of Standards in Systems and Synthetic Biology: Status and Developments in 2017.

PubMed

Schreiber, Falk; Bader, Gary D; Gleeson, Padraig; Golebiewski, Martin; Hucka, Michael; Keating, Sarah M; Novère, Nicolas Le; Myers, Chris; Nickerson, David; Sommer, Björn; Waltemath, Dagmar

2018-03-29

Standards are essential to the advancement of Systems and Synthetic Biology. COMBINE provides a formal body and a centralised platform to help develop and disseminate relevant standards and related resources. The regular special issue of the Journal of Integrative Bioinformatics aims to support the exchange, distribution and archiving of these standards by providing unified, easily citable access. This paper provides an overview of existing COMBINE standards and presents developments of the last year.

Advanced systems biology methods in drug discovery and translational biomedicine.

PubMed

Zou, Jun; Zheng, Ming-Wu; Li, Gen; Su, Zhi-Guang

2013-01-01

Systems biology is in an exponential development stage in recent years and has been widely utilized in biomedicine to better understand the molecular basis of human disease and the mechanism of drug action. Here, we discuss the fundamental concept of systems biology and its two computational methods that have been commonly used, that is, network analysis and dynamical modeling. The applications of systems biology in elucidating human disease are highlighted, consisting of human disease networks, treatment response prediction, investigation of disease mechanisms, and disease-associated gene prediction. In addition, important advances in drug discovery, to which systems biology makes significant contributions, are discussed, including drug-target networks, prediction of drug-target interactions, investigation of drug adverse effects, drug repositioning, and drug combination prediction. The systems biology methods and applications covered in this review provide a framework for addressing disease mechanism and approaching drug discovery, which will facilitate the translation of research findings into clinical benefits such as novel biomarkers and promising therapies.

Data-intensive drug development in the information age: applications of Systems Biology/Pharmacology/Toxicology.

PubMed

Kiyosawa, Naoki; Manabe, Sunao

2016-01-01

Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. R&D productivity of drug development projects depends on 1) the value of the drug concept and 2) data and in-depth knowledge that are used rationally to evaluate the drug concept's validity. A model-based data-intensive drug development approach is a key competitive factor used by innovative pharmaceutical companies to reduce information bias and rationally demonstrate the value of drug concepts. Owing to the accumulation of publicly available biomedical information, our understanding of the pathophysiological mechanisms of diseases has developed considerably; it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful for these purposes. Furthermore, applying Systems Pharmacology enables dynamic simulation of drug responses, from which key research questions to be addressed in the subsequent studies can be adequately informed. Application of Systems Biology/Pharmacology to toxicology research, namely Systems Toxicology, should considerably improve the predictability of drug-induced toxicities in clinical situations that are difficult to predict from conventional preclinical toxicology studies. Systems Biology/Pharmacology/Toxicology models can be continuously improved using iterative learn-confirm processes throughout preclinical and clinical drug discovery and development processes. Successful implementation of data-intensive drug development approaches requires cultivation of an adequate R&D culture to appreciate this approach.

Half dozen of one, six billion of the other: What can small- and large-scale molecular systems biology learn from one another?

PubMed

Mellis, Ian A; Raj, Arjun

2015-10-01

Small-scale molecular systems biology, by which we mean the understanding of a how a few parts work together to control a particular biological process, is predicated on the assumption that cellular regulation is arranged in a circuit-like structure. Results from the omics revolution have upset this vision to varying degrees by revealing a high degree of interconnectivity, making it difficult to develop a simple, circuit-like understanding of regulatory processes. We here outline the limitations of the small-scale systems biology approach with examples from research into genetic algorithms, genetics, transcriptional network analysis, and genomics. We also discuss the difficulties associated with deriving true understanding from the analysis of large data sets and propose that the development of new, intelligent, computational tools may point to a way forward. Throughout, we intentionally oversimplify and talk about things in which we have little expertise, and it is likely that many of our arguments are wrong on one level or another. We do believe, however, that developing a true understanding via molecular systems biology will require a fundamental rethinking of our approach, and our goal is to provoke thought along these lines. © 2015 Mellis and Raj; Published by Cold Spring Harbor Laboratory Press.

Synergism of Nanomaterials with Physical Stimuli for Biology and Medicine.

PubMed

Shin, Tae-Hyun; Cheon, Jinwoo

2017-03-21

Developing innovative tools that facilitate the understanding of sophisticated biological systems has been one of the Holy Grails in the physical and biological sciences. In this Commentary, we discuss recent advances, opportunities, and challenges in the use of nanomaterials as a precision tool for biology and medicine.

On the making of a system theory of life: Paul A Weiss and Ludwig von Bertalanffy's conceptual connection.

PubMed

Drack, Manfred; Apfalter, Wilfried; Pouvreau, David

2007-12-01

In this article, we review how two eminent Viennese system thinkers, Paul A Weiss and Ludwig von Bertalanffy, began to develop their own perspectives toward a system theory of life in the 1920s. Their work is especially rooted in experimental biology as performed at the Biologische Versuchsanstalt, as well as in philosophy, and they converge in basic concepts. We underline the conceptual connections of their thinking, among them the organism as an organized system, hierarchical organization, and primary activity. With their system thinking, both biologists shared a strong desire to overcome what they viewed as a "mechanistic" approach in biology. Their interpretations are relevant to the renaissance of system thinking in biology--"systems biology." Unless otherwise noted, all translations are our own.

Insects as test systems for assessing the potential role of microgravity in biological development and evolution

NASA Astrophysics Data System (ADS)

Vernós, I.; Carratalá, M.; González-Jurado, J.; Valverde, J. R.; Calleja, M.; Domingo, A.; Vinós, J.; Cervera, M.; Marco, R.

Gravity and radiation are undoubtedly the two major environmental factors altered in space. Gravity is a weak force, which creates a permanent potential field acting on the mass of biological systems and their cellular components, strongly reduced in space flights. Developmental systems, particularly at very early stages, provide the larger cellular compartments known, where the effects of alterations in the size of the gravity vector on living organisms can be more effectively tested. The insects, one of the more highly evolved classes of animals in which early development occurs in a syncytial embryo, are systems particularly well suited to test these effects and the specific developmental mechanisms affected. Furthermore, they share some basic features such as small size, short life cycles, relatively high radio-resistance, etc. and show a diversity of developmental strategies and tempos advantageous in experiments of this type in space. Drosophila melanogaster, the current biological paradigm to study development, with so much genetic and evolutionary background available, is clearly the reference organism for these studies. The current evidence on the effects of the physical parameters altered in space flights on insect development indicate a surprising correlation between effects seen on the fast developing and relatively small Drosophila embryo and the more slowly developing and large Carausius morosus system. In relation to the issue of the importance of developmental and environmental constraints in biological evolution, still the missing link in current evolutionary thinking, insects and space facilities for long-term experiments could provide useful experimental settings where to critically assess how development and evolution may be interconnected. Finally, it has to be pointed out that since there are experimental data indicating a possible synergism between microgravity and space radiation, possible effects of space radiation should be taken into account in the planning and evaluation of experiments designed to test the potential role of microgravity on biological development and evolution.

Generation and characterization of biological aerosols for laser measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Yung-Sung; Barr, E.B.

1995-12-01

Concerns for proliferation of biological weapons including bacteria, fungi, and viruses have prompted research and development on methods for the rapid detection of biological aerosols in the field. Real-time instruments that can distinguish biological aerosols from background dust would be especially useful. Sandia National Laboratories (SNL) is developing a laser-based, real-time instrument for rapid detection of biological aerosols, and ITRI is working with SNL scientists and engineers to evaluate this technology for a wide range of biological aerosols. This paper describes methods being used to generate the characterize the biological aerosols for these tests. In summary, a biosafe system hasmore » been developed for generating and characterizing biological aerosols and using those aerosols to test the SNL laser-based real-time instrument. Such tests are essential in studying methods for rapid detection of airborne biological materials.« less

Assessment and management of soil microbial community structure for disease suppression.

PubMed

Mazzola, Mark

2004-01-01

Identification of the biological properties contributing to the function of suppressive soils is a necessary first step to the management of such systems for use in the control of soilborne diseases. The development and application of molecular methods for the characterization and monitoring of soil microbial properties will enable a more rapid and detailed assessment of the biological nature of soil suppressiveness. Although suppressive soils have provided a wealth of microbial resources that have subsequently been applied for the biological control of soilborne plant pathogens, the full functional capabilities of the phenomena have not been realized in production agricultural ecosystems. Cultural practices, such as the application of soil amendments, have the capacity to enhance disease suppression, though the biological modes of action may vary from that initially resident to the soil. Plants have a distinct impact on characteristics and activity of resident soil microbial communities, and therefore play an important role in determining the development of the disease-suppressive state. Likewise, plant genotype will modulate these same biological communities, and should be considered when developing strategies to exploit the potential of such a natural disease control system. Implementation of consistently effective practices to manage this resource in an economically and environmentally feasible manner will require more detailed investigation of these biologically complex systems and refinement of currently available methodologies.

Parameter estimation using meta-heuristics in systems biology: a comprehensive review.

PubMed

Sun, Jianyong; Garibaldi, Jonathan M; Hodgman, Charlie

2012-01-01

This paper gives a comprehensive review of the application of meta-heuristics to optimization problems in systems biology, mainly focussing on the parameter estimation problem (also called the inverse problem or model calibration). It is intended for either the system biologist who wishes to learn more about the various optimization techniques available and/or the meta-heuristic optimizer who is interested in applying such techniques to problems in systems biology. First, the parameter estimation problems emerging from different areas of systems biology are described from the point of view of machine learning. Brief descriptions of various meta-heuristics developed for these problems follow, along with outlines of their advantages and disadvantages. Several important issues in applying meta-heuristics to the systems biology modelling problem are addressed, including the reliability and identifiability of model parameters, optimal design of experiments, and so on. Finally, we highlight some possible future research directions in this field.

Multi-agent-based bio-network for systems biology: protein-protein interaction network as an example.

PubMed

Ren, Li-Hong; Ding, Yong-Sheng; Shen, Yi-Zhen; Zhang, Xiang-Feng

2008-10-01

Recently, a collective effort from multiple research areas has been made to understand biological systems at the system level. This research requires the ability to simulate particular biological systems as cells, organs, organisms, and communities. In this paper, a novel bio-network simulation platform is proposed for system biology studies by combining agent approaches. We consider a biological system as a set of active computational components interacting with each other and with an external environment. Then, we propose a bio-network platform for simulating the behaviors of biological systems and modelling them in terms of bio-entities and society-entities. As a demonstration, we discuss how a protein-protein interaction (PPI) network can be seen as a society of autonomous interactive components. From interactions among small PPI networks, a large PPI network can emerge that has a remarkable ability to accomplish a complex function or task. We also simulate the evolution of the PPI networks by using the bio-operators of the bio-entities. Based on the proposed approach, various simulators with different functions can be embedded in the simulation platform, and further research can be done from design to development, including complexity validation of the biological system.

Biological satellite scientific devices

NASA Astrophysics Data System (ADS)

Perepech, B. L.; Rumiantsev, V. P.; Galkin, V. M.; Shakhvorostov, S. V.; Rvachev, S. S.

1991-02-01

The paper describes the NA SBS 9 systems developed for the ninth Cosmos-2044 biological test mission. The NA SBS 9 life support systems designed for monkeys and rats follow standard design of BIOS-Vivarium and BIOS-Primate units. The main features of NA SBS 9 include the use of a recently developed HF physiological data recorder Skat-3; the incorporation into BIOS-Primate of two units intended for biorhythmic studies (the BBI-Zh system for studying beetles and the VITALOG developed by NASA for studies on monkeys); and a new version of BIOS-Primate system incorporating a capacitance-link and an inductance-link temperature transmitters and a brain tissue oxygen tension control channel.

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-off on Phenotype Robustness in Biological Networks Part I: Gene Regulatory Networks in Systems and Evolutionary Biology

PubMed Central

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties observed in biological systems at different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be enough to confer intrinsic robustness in order to tolerate intrinsic parameter fluctuations, genetic robustness for buffering genetic variations, and environmental robustness for resisting environmental disturbances. With this, the phenotypic stability of biological network can be maintained, thus guaranteeing phenotype robustness. This paper presents a survey on biological systems and then develops a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation in systems and evolutionary biology. Further, from the unifying mathematical framework, it was discovered that the phenotype robustness criterion for biological networks at different levels relies upon intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness. When this is true, the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in systems and evolutionary biology can also be investigated through their corresponding phenotype robustness criterion from the systematic point of view. PMID:23515240

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-off on Phenotype Robustness in Biological Networks Part I: Gene Regulatory Networks in Systems and Evolutionary Biology.

PubMed

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties observed in biological systems at different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be enough to confer intrinsic robustness in order to tolerate intrinsic parameter fluctuations, genetic robustness for buffering genetic variations, and environmental robustness for resisting environmental disturbances. With this, the phenotypic stability of biological network can be maintained, thus guaranteeing phenotype robustness. This paper presents a survey on biological systems and then develops a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation in systems and evolutionary biology. Further, from the unifying mathematical framework, it was discovered that the phenotype robustness criterion for biological networks at different levels relies upon intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness. When this is true, the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in systems and evolutionary biology can also be investigated through their corresponding phenotype robustness criterion from the systematic point of view.

Reputation-based collaborative network biology.

PubMed

Binder, Jean; Boue, Stephanie; Di Fabio, Anselmo; Fields, R Brett; Hayes, William; Hoeng, Julia; Park, Jennifer S; Peitsch, Manuel C

2015-01-01

A pilot reputation-based collaborative network biology platform, Bionet, was developed for use in the sbv IMPROVER Network Verification Challenge to verify and enhance previously developed networks describing key aspects of lung biology. Bionet was successful in capturing a more comprehensive view of the biology associated with each network using the collective intelligence and knowledge of the crowd. One key learning point from the pilot was that using a standardized biological knowledge representation language such as BEL is critical to the success of a collaborative network biology platform. Overall, Bionet demonstrated that this approach to collaborative network biology is highly viable. Improving this platform for de novo creation of biological networks and network curation with the suggested enhancements for scalability will serve both academic and industry systems biology communities.

Photonics and bioinspiration

NASA Astrophysics Data System (ADS)

Lewis, Keith

2014-10-01

Biological systems exploiting light have benefitted from thousands of years of genetic evolution and can provide insight to support the development of new approaches for imaging, image processing and communication. For example, biological vision systems can provide significant diversity, yet are able to function with only a minimal degree of neural processing. Examples will be described underlying the processes used to support the development of new concepts for photonic systems, ranging from uncooled bolometers and tunable filters, to asymmetric free-space optical communication systems and new forms of camera capable of simultaneously providing spectral and polarimetric diversity.

Development of sensory systems in zebrafish (Danio rerio)

NASA Technical Reports Server (NTRS)

Moorman, S. J.

2001-01-01

Zebrafish possess all of the classic sensory modalities: taste, tactile, smell, balance, vision, and hearing. For each sensory system, this article provides a brief overview of the system in the adult zebrafish followed by a more detailed overview of the development of the system. By far the majority of studies performed in each of the sensory systems of the zebrafish have involved some aspect of molecular biology or genetics. Although molecular biology and genetics are not major foci of the paper, brief discussions of some of the mutant strains of zebrafish that have developmental defects in each specific sensory system are included. The development of the sensory systems is only a small sampling of the work being done using zebrafish and provides a mere glimpse of the potential of this model for the study of vertebrate development, physiology, and human disease.

Adverse outcome pathway (AOP) development I: Strategies and principles

EPA Science Inventory

An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically-supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organizatio...

Introduction to landscape influences on stream habitats and biological assemblages

EPA Science Inventory

Viewing river systems within a landscape context is a relatively new and rapidly developing approach to river ecology. Although the linkages among landscapes and associated physicochemical and biological characteristics of rivers have long been recognized, the development of con...

Biologically active chitosan systems for tissue engineering and regenerative medicine.

PubMed

Jiang, Tao; Kumbar, Sangamesh G; Nair, Lakshmi S; Laurencin, Cato T

2008-01-01

Biodegradable polymeric scaffolds are widely used as a temporary extracellular matrix in tissue engineering and regenerative medicine. By physical adsorption of biomolecules on scaffold surface, physical entrapment of biomolecules in polymer microspheres or hydrogels, and chemical immobilization of oligopeptides or proteins on biomaterials, biologically active biomaterials and scaffolds can be derived. These bioactive systems show great potential in tissue engineering in rendering bioactivity and/or specificity to scaffolds. This review highlights some of the biologically active chitosan systems for tissue engineering application and the associated strategies to develop such bioactive chitosan systems.

A Case Study of Web-Based Instruction (WBI): The Effectiveness of Using Frontpage Feedback System (FFS) as Metacognition Strategy for Freshmen Biology Teaching

ERIC Educational Resources Information Center

Wang, Tzu-Hua; Wang, Wei-Lung; Wang, Kuo-Hua; Huang, Hsih-Chieh

2004-01-01

This research aims to develop a Metacognition strategy for Web-Based Instruction (WBI) to stimulate reflective questions in biology learning to run Frontpage Feedback System (FFS) embedded in web pages, and thus to evaluate the influence of this internet-teaching style on biology learning among freshmen. According to the questionnaire survey, we…

Modeling biology with HDL languages: a first step toward a genetic design automation tool inspired from microelectronics.

PubMed

Gendrault, Yves; Madec, Morgan; Lallement, Christophe; Haiech, Jacques

2014-04-01

Nowadays, synthetic biology is a hot research topic. Each day, progresses are made to improve the complexity of artificial biological functions in order to tend to complex biodevices and biosystems. Up to now, these systems are handmade by bioengineers, which require strong technical skills and leads to nonreusable development. Besides, scientific fields that share the same design approach, such as microelectronics, have already overcome several issues and designers succeed in building extremely complex systems with many evolved functions. On the other hand, in systems engineering and more specifically in microelectronics, the development of the domain has been promoted by both the improvement of technological processes and electronic design automation tools. The work presented in this paper paves the way for the adaptation of microelectronics design tools to synthetic biology. Considering the similarities and differences between the synthetic biology and microelectronics, the milestones of this adaptation are described. The first one concerns the modeling of biological mechanisms. To do so, a new formalism is proposed, based on an extension of the generalized Kirchhoff laws to biology. This way, a description of all biological mechanisms can be made with languages widely used in microelectronics. Our approach is therefore successfully validated on specific examples drawn from the literature.

End-to-End Data System Architecture for the Space Station Biological Research Project

NASA Technical Reports Server (NTRS)

Mian, Arshad; Scimemi, Sam; Adeni, Kaiser; Picinich, Lou; Ramos, Rubin (Technical Monitor)

1998-01-01

The Space Station Biological Research Project (SSBRP) Is developing hardware referred to as the "facility" for providing life sciences research capability on the International Space Station. This hardware includes several biological specimen habitats, habitat holding racks, a centrifuge and a glovebox. An SSBRP end to end data system architecture has been developed to allow command and control of the facility from the ground, either with crew assistance or autonomously. The data system will be capable of handling commands, sensor data, and video from multiple cameras. The data will traverse through several onboard and ground networks and processing entities including the SSBRP and Space Station onboard and ground data systems. A large number of onboard and ground (,entities of the data system are being developed by the Space Station Program, other NASA centers and the International Partners. The SSBRP part of the system which includes the habitats, holding racks, and the ground operations center, User Operations Facility (UOF) will be developed by a multitude of geographically distributed development organizations. The SSBRP has the responsibility to define the end to end data and communications systems to make the interfaces manageable and verifiable with multiple contractors with widely varying development constraints and schedules. This paper provides an overview of the SSBRP end-to-end data system. Specifically, it describes the hardware, software and functional interactions of individual systems, and interface requirements among various entities of the end-to-end system.

Development of the Special Operations Combat Management System

DTIC Science & Technology

1999-08-01

Distribution Unlimited Prepared for U. S. Army Soldier and Biological Chemical Command Soldier Systems Center Natick, Massachusetts 01760-5020 19990826 022...Army Soldier and Biological Chemical Command, Soldier Systems Center, ATTN: AMSSB-RSS-D(N) (H. Girolamo), Natick, MA 01760-5020 14. ABSTRACT The...system design, integration and test. American Megatrends Inc. provided the motherboard circuit design, layout and production. Tactical Technologies Inc

Revealing complex function, process and pathway interactions with high-throughput expression and biological annotation data.

PubMed

Singh, Nitesh Kumar; Ernst, Mathias; Liebscher, Volkmar; Fuellen, Georg; Taher, Leila

2016-10-20

The biological relationships both between and within the functions, processes and pathways that operate within complex biological systems are only poorly characterized, making the interpretation of large scale gene expression datasets extremely challenging. Here, we present an approach that integrates gene expression and biological annotation data to identify and describe the interactions between biological functions, processes and pathways that govern a phenotype of interest. The product is a global, interconnected network, not of genes but of functions, processes and pathways, that represents the biological relationships within the system. We validated our approach on two high-throughput expression datasets describing organismal and organ development. Our findings are well supported by the available literature, confirming that developmental processes and apoptosis play key roles in cell differentiation. Furthermore, our results suggest that processes related to pluripotency and lineage commitment, which are known to be critical for development, interact mainly indirectly, through genes implicated in more general biological processes. Moreover, we provide evidence that supports the relevance of cell spatial organization in the developing liver for proper liver function. Our strategy can be viewed as an abstraction that is useful to interpret high-throughput data and devise further experiments.

[Biotechnological functional systems].

PubMed

Bokser, O Ia

1999-01-01

Based on the theory of functional systems and a concept of the quantum system of behavior, studies of the quantumsystems were conducted. Their structure, the interaction of biological and technical sections were analyzed. Mathematical, biophysical, and experimental models were designed. The paper shows that biotechnical quantumsystems are involved in the formation of biological feedback. A system with imperative feedback from the programmed and introduced current results of efforts has been developed and put into practice for the self-regulation of muscle tension. Training by using this biological feedback system causes a stable increase in the perception rate of proprioceptive stimulus in examinees (operates, sportsmen, neurological patients).

Biological sludge solubilisation for reduction of excess sludge production in wastewater treatment process.

PubMed

Yamaguchi, T; Yao, Y; Kihara, Y

2006-01-01

A novel sludge disintegration system (JFE-SD system) was developed for the reduction of excess sludge production in wastewater treatment plants. Chemical and biological treatments were applied to disintegrate excess sludge. At the first step, to enhance biological disintegration, the sludge was pretreated with alkali. At the second step, the sludge was disintegrated by biological treatment. Many kinds of sludge degrading microorganisms integrated the sludge. The efficiency of the new sludge disintegration system was confirmed in a full-scale experiment. The JFE-SD system reduced excess sludge production by approximately 50% during the experimental period. The quality of effluent was kept at quite a good level. Economic analysis revealed that this system could significantly decrease the excess sludge treatment cost.

Engineering biological systems using automated biofoundries.

PubMed

Chao, Ran; Mishra, Shekhar; Si, Tong; Zhao, Huimin

2017-07-01

Engineered biological systems such as genetic circuits and microbial cell factories have promised to solve many challenges in the modern society. However, the artisanal processes of research and development are slow, expensive, and inconsistent, representing a major obstacle in biotechnology and bioengineering. In recent years, biological foundries or biofoundries have been developed to automate design-build-test engineering cycles in an effort to accelerate these processes. This review summarizes the enabling technologies for such biofoundries as well as their early successes and remaining challenges. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Advanced biologically plausible algorithms for low-level image processing

NASA Astrophysics Data System (ADS)

Gusakova, Valentina I.; Podladchikova, Lubov N.; Shaposhnikov, Dmitry G.; Markin, Sergey N.; Golovan, Alexander V.; Lee, Seong-Whan

1999-08-01

At present, in computer vision, the approach based on modeling the biological vision mechanisms is extensively developed. However, up to now, real world image processing has no effective solution in frameworks of both biologically inspired and conventional approaches. Evidently, new algorithms and system architectures based on advanced biological motivation should be developed for solution of computational problems related to this visual task. Basic problems that should be solved for creation of effective artificial visual system to process real world imags are a search for new algorithms of low-level image processing that, in a great extent, determine system performance. In the present paper, the result of psychophysical experiments and several advanced biologically motivated algorithms for low-level processing are presented. These algorithms are based on local space-variant filter, context encoding visual information presented in the center of input window, and automatic detection of perceptually important image fragments. The core of latter algorithm are using local feature conjunctions such as noncolinear oriented segment and composite feature map formation. Developed algorithms were integrated into foveal active vision model, the MARR. It is supposed that proposed algorithms may significantly improve model performance while real world image processing during memorizing, search, and recognition.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sussman, Michael R.

The 2012 Gordon Conference on Plant Molecular Biology will present cutting-edge research on molecular aspects of plant growth and development, with particular emphasis on recent discoveries in molecular mechanisms involved with plant signaling systems. The Conference will feature a wide range of topics in plant molecular biology including hormone receptors and early events in hormone signaling, plant perception of and response to plant pathogen and symbionts, as well as technological and biological aspects of epigenomics particularly as it relates to signaling systems that regulate plant growth and development. Genomic approaches to plant signaling will be emphasized, including genomic profiling technologiesmore » for quantifying various biological subsystems, such as the epigenome, transcriptome, phosphorylome, and metabolome. The meeting will include an important session devoted to answering the question, "What are the biological and technological limits of plant breeding/genetics, and how can they be solved"?« less

Promoting new concepts of skincare via skinomics and systems biology-From traditional skincare and efficacy-based skincare to precision skincare.

PubMed

Jiang, Biao; Jia, Yan; He, Congfen

2018-05-11

Traditional skincare involves the subjective classification of skin into 4 categories (oily, dry, mixed, and neutral) prior to skin treatment. Following the development of noninvasive methods in skin and skin imaging technology, scientists have developed efficacy-based skincare products based on the physiological characteristics of skin under different conditions. Currently, the emergence of skinomics and systems biology has facilitated the development of precision skincare. In this article, the evolution of skincare based on the physiological states of the skin (from traditional skincare and efficacy-based skincare to precision skincare) is described. In doing so, we highlight skinomics and systems biology, with particular emphasis on the importance of skin lipidomics and microbiomes in precision skincare. The emerging trends of precision skincare are anticipated. © 2018 Wiley Periodicals, Inc.

A system to evaluate the scientific quality of biological and restoration objectives using National Wildlife Refuge Comprehensive Conservation Plans as a case study

USGS Publications Warehouse

Schroeder, R.L.

2006-01-01

It is widely accepted that plans for restoration projects should contain specific, measurable, and science-based objectives to guide restoration efforts. The United States Fish and Wildlife Service (USFWS) is in the process of developing Comprehensive Conservation Plans (CCPs) for more than 500 units in the National Wildlife Refuge System (NWRS). These plans contain objectives for biological and ecosystem restoration efforts on the refuges. Based on USFWS policy, a system was developed to evaluate the scientific quality of such objectives based on three critical factors: (1) Is the objective specific, measurable, achievable, results-oriented, and time-fixed? (2) What is the extent of the rationale that explains the assumptions, logic, and reasoning for the objective? (3) How well was available science used in the development of the objective? The evaluation system scores each factor on a scale of 1 (poor) to 4 (excellent) according to detailed criteria. The biological and restoration objectives from CCPs published as of September 2004 (60 total) were evaluated. The overall average score for all biological and restoration objectives was 1.73. Average scores for each factor were: Factor 1-1.97; Factor 2-1.86; Factor 3-1.38. The overall scores increased from 1997 to 2004. Future restoration efforts may benefit by using this evaluation system during the process of plan development, to ensure that biological and restoration objectives are of the highest scientific quality possible prior to the implementation of restoration plans, and to allow for improved monitoring and adaptive management.

Biomimicry, Biofabrication, and Biohybrid Systems: The Emergence and Evolution of Biological Design.

PubMed

Raman, Ritu; Bashir, Rashid

2017-10-01

The discipline of biological design has a relatively short history, but has undergone very rapid expansion and development over that time. This Progress Report outlines the evolution of this field from biomimicry to biofabrication to biohybrid systems' design, showcasing how each subfield incorporates bioinspired dynamic adaptation into engineered systems. Ethical implications of biological design are discussed, with an emphasis on establishing responsible practices for engineering non-natural or hypernatural functional behaviors in biohybrid systems. This report concludes with recommendations for implementing biological design into educational curricula, ensuring effective and responsible practices for the next generation of engineers and scientists. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biology Curriculum Reform in Venezuela.

ERIC Educational Resources Information Center

Rondon, Leonor Mariasole

2001-01-01

Describes science in the Venezuelan school system which reflects on the process of development followed to design and validate the Biology Study Programs (BSP) with the emphasis on the relevance of curricular changes proposed in biological science for secondary education. (Contains 19 references.) (ASK)

Insects as test systems for assessing the potential role of microgravity in biological development and evolution.

PubMed

Vernós, I; Carratalá, M; González-Jurado, J; Valverde, J R; Calleja, M; Domingo, A; Vinós, J; Cervera, M; Marco, R

1989-01-01

Gravity and radiation are undoubtedly the two major environmental factors altered in space. Gravity is a weak force, which creates a permanent potential field acting on the mass of biological systems and their cellular components, strongly reduced in space flights. Developmental systems, particularly at very early stages, provide the larger cellular compartments known, where the effects of alterations in the size of the gravity vector on living organisms can be more effectively tested. The insects, one of the more highly evolved classes of animals in which early development occurs in a syncytial embryo, are systems particularly well suited to test these effects and the specific developmental mechanisms affected. Furthermore, they share some basic features such as small size, short life cycles, relatively high radio-resistance, etc. and show a diversity of developmental strategies and tempos advantageous in experiments of this type in space. Drosophila melanogaster, the current biological paradigm to study development, with so much genetic and evolutionary background available, is clearly the reference organism for these studies. The current evidence on the effects of the physical parameters altered in space flights on insect development indicate a surprising correlation between effects seen on the fast developing and relatively small Drosophila embryo and the more slowly developing and large Carausius morosus system. In relation to the issue of the importance of developmental and environmental constraints in biological evolution, still the missing link in current evolutionary thinking, insects and space facilities for long-term experiments could provide useful experimental settings where to critically assess how development and evolution may be interconnected. Finally, it has to be pointed out that since there are experimental data indicating a possible synergism between microgravity and space radiation, possible effects of space radiation should be taken into account in the planning and evaluation of experiments designed to test the potential role of microgravity on biological developmental and evolution.

CURRENT PRACTICES IN QSAR DEVELOPMENT AND APPLICATIONS

EPA Science Inventory

Current Practices in QSAR Development and Applications

Although it is commonly assumed that the structure and properties of a single chemical determines its activity in a particular biological system, it is only through study of how biological activity varies with changes...

[Biological therapies in systemic lupus erythematosus].

PubMed

Cairoli, Ernesto; Espinosa, Gerard; Cervera, Ricard

2010-07-01

The immunosuppressive agents used in patients with systemic lupus erythematosus (SLE) have significantly improved prognosis. However, it is necessary to develop more specific immunosuppressive treatments with less toxicity. Better understanding of the mechanisms involved in the loss of tolerance in autoimmune diseases has contributed to the development of potential new treatments called biologic therapies. The targets of these biological therapies are directed toward the B cell depletion, interference in the co-stimulation signals and the blockade of cytokines. Therapies using anti-CD20 monoclonal antibodies have shown satisfactory results especially in patients with SLE refractory to conventional treatment. The biological therapies provide encouraging results that represent a possible option in the treatment of refractory patients as well as a potential therapy in the future management of SLE.

Logic Gate Operation by DNA Translocation through Biological Nanopores.

PubMed

Yasuga, Hiroki; Kawano, Ryuji; Takinoue, Masahiro; Tsuji, Yutaro; Osaki, Toshihisa; Kamiya, Koki; Miki, Norihisa; Takeuchi, Shoji

2016-01-01

Logical operations using biological molecules, such as DNA computing or programmable diagnosis using DNA, have recently received attention. Challenges remain with respect to the development of such systems, including label-free output detection and the rapidity of operation. Here, we propose integration of biological nanopores with DNA molecules for development of a logical operating system. We configured outputs "1" and "0" as single-stranded DNA (ssDNA) that is or is not translocated through a nanopore; unlabeled DNA was detected electrically. A negative-AND (NAND) operation was successfully conducted within approximately 10 min, which is rapid compared with previous studies using unlabeled DNA. In addition, this operation was executed in a four-droplet network. DNA molecules and associated information were transferred among droplets via biological nanopores. This system would facilitate linking of molecules and electronic interfaces. Thus, it could be applied to molecular robotics, genetic engineering, and even medical diagnosis and treatment.

BIOCHEMISTRY OF MOBILE ZINC AND NITRIC OXIDE REVEALED BY FLUORESCENT SENSORS

PubMed Central

Pluth, Michael D.; Tomat, Elisa; Lippard, Stephen J.

2010-01-01

Biologically mobile zinc and nitric oxide (NO) are two prominent examples of inorganic compounds involved in numerous signaling pathways in living systems. In the past decade, a synergy of regulation, signaling, and translocation of these two species has emerged in several areas of human physiology, providing additional incentive for developing adequate detection systems for Zn(II) ions and NO in biological specimens. Fluorescent probes for both of these bioinorganic analytes provide excellent tools for their detection, with high spatial and temporal resolution. We review the most widely used fluorescent sensors for biological zinc and nitric oxide, together with promising new developments and unmet needs of contemporary Zn(II) and NO biological imaging. The interplay between zinc and nitric oxide in the nervous, cardiovascular, and immune systems is highlighted to illustrate the contributions of selective fluorescent probes to the study of these two important bioinorganic analytes. PMID:21675918

Tools for visually exploring biological networks.

PubMed

Suderman, Matthew; Hallett, Michael

2007-10-15

Many tools exist for visually exploring biological networks including well-known examples such as Cytoscape, VisANT, Pathway Studio and Patika. These systems play a key role in the development of integrative biology, systems biology and integrative bioinformatics. The trend in the development of these tools is to go beyond 'static' representations of cellular state, towards a more dynamic model of cellular processes through the incorporation of gene expression data, subcellular localization information and time-dependent behavior. We provide a comprehensive review of the relative advantages and disadvantages of existing systems with two goals in mind: to aid researchers in efficiently identifying the appropriate existing tools for data visualization; to describe the necessary and realistic goals for the next generation of visualization tools. In view of the first goal, we provide in the Supplementary Material a systematic comparison of more than 35 existing tools in terms of over 25 different features. Supplementary data are available at Bioinformatics online.

Logic Gate Operation by DNA Translocation through Biological Nanopores

PubMed Central

Takinoue, Masahiro; Tsuji, Yutaro; Osaki, Toshihisa; Kamiya, Koki; Miki, Norihisa; Takeuchi, Shoji

2016-01-01

Logical operations using biological molecules, such as DNA computing or programmable diagnosis using DNA, have recently received attention. Challenges remain with respect to the development of such systems, including label-free output detection and the rapidity of operation. Here, we propose integration of biological nanopores with DNA molecules for development of a logical operating system. We configured outputs “1” and “0” as single-stranded DNA (ssDNA) that is or is not translocated through a nanopore; unlabeled DNA was detected electrically. A negative-AND (NAND) operation was successfully conducted within approximately 10 min, which is rapid compared with previous studies using unlabeled DNA. In addition, this operation was executed in a four-droplet network. DNA molecules and associated information were transferred among droplets via biological nanopores. This system would facilitate linking of molecules and electronic interfaces. Thus, it could be applied to molecular robotics, genetic engineering, and even medical diagnosis and treatment. PMID:26890568

Synthetic biology: new engineering rules for an emerging discipline

PubMed Central

Andrianantoandro, Ernesto; Basu, Subhayu; Karig, David K; Weiss, Ron

2006-01-01

Synthetic biologists engineer complex artificial biological systems to investigate natural biological phenomena and for a variety of applications. We outline the basic features of synthetic biology as a new engineering discipline, covering examples from the latest literature and reflecting on the features that make it unique among all other existing engineering fields. We discuss methods for designing and constructing engineered cells with novel functions in a framework of an abstract hierarchy of biological devices, modules, cells, and multicellular systems. The classical engineering strategies of standardization, decoupling, and abstraction will have to be extended to take into account the inherent characteristics of biological devices and modules. To achieve predictability and reliability, strategies for engineering biology must include the notion of cellular context in the functional definition of devices and modules, use rational redesign and directed evolution for system optimization, and focus on accomplishing tasks using cell populations rather than individual cells. The discussion brings to light issues at the heart of designing complex living systems and provides a trajectory for future development. PMID:16738572

Synthetic biology: new engineering rules for an emerging discipline.

PubMed

Andrianantoandro, Ernesto; Basu, Subhayu; Karig, David K; Weiss, Ron

2006-01-01

Synthetic biologists engineer complex artificial biological systems to investigate natural biological phenomena and for a variety of applications. We outline the basic features of synthetic biology as a new engineering discipline, covering examples from the latest literature and reflecting on the features that make it unique among all other existing engineering fields. We discuss methods for designing and constructing engineered cells with novel functions in a framework of an abstract hierarchy of biological devices, modules, cells, and multicellular systems. The classical engineering strategies of standardization, decoupling, and abstraction will have to be extended to take into account the inherent characteristics of biological devices and modules. To achieve predictability and reliability, strategies for engineering biology must include the notion of cellular context in the functional definition of devices and modules, use rational redesign and directed evolution for system optimization, and focus on accomplishing tasks using cell populations rather than individual cells. The discussion brings to light issues at the heart of designing complex living systems and provides a trajectory for future development.

Metabolic modelling in the development of cell factories by synthetic biology

PubMed Central

Jouhten, Paula

2012-01-01

Cell factories are commonly microbial organisms utilized for bioconversion of renewable resources to bulk or high value chemicals. Introduction of novel production pathways in chassis strains is the core of the development of cell factories by synthetic biology. Synthetic biology aims to create novel biological functions and systems not found in nature by combining biology with engineering. The workflow of the development of novel cell factories with synthetic biology is ideally linear which will be attainable with the quantitative engineering approach, high-quality predictive models, and libraries of well-characterized parts. Different types of metabolic models, mathematical representations of metabolism and its components, enzymes and metabolites, are useful in particular phases of the synthetic biology workflow. In this minireview, the role of metabolic modelling in synthetic biology will be discussed with a review of current status of compatible methods and models for the in silico design and quantitative evaluation of a cell factory. PMID:24688669

Synthetic biology: Emerging bioengineering in Indonesia

NASA Astrophysics Data System (ADS)

Suhandono, Sony

2017-05-01

The development of synthetic biology will shape the new era of science and technology. It is an emerging bioengineering technique involving genetic engineering which can alter the phenotype and behavior of the cell or the new product. Synthetic biology may produce biomaterials, drugs, vaccines, biosensors, and even a recombinant secondary metabolite used in herbal and complementary medicine, such as artemisinin, a malaria drug which is usually extracted from the plant Artemisia annua. The power of synthetic biology has encouraged scientists in Indonesia, and is still in early development. This paper also covers some research from an Indonesian research institute in synthetic biology such as observing the production of bio surfactants and the enhanced production of artemisinin using a transient expression system. Synthetic biology development in Indonesia may also be related to the iGEM competition, a large synthetic biology research competition which was attended by several universities in Indonesia. The application of synthetic biology for drug discovery will be discussed.

Agent-based modelling in synthetic biology.

PubMed

Gorochowski, Thomas E

2016-11-30

Biological systems exhibit complex behaviours that emerge at many different levels of organization. These span the regulation of gene expression within single cells to the use of quorum sensing to co-ordinate the action of entire bacterial colonies. Synthetic biology aims to make the engineering of biology easier, offering an opportunity to control natural systems and develop new synthetic systems with useful prescribed behaviours. However, in many cases, it is not understood how individual cells should be programmed to ensure the emergence of a required collective behaviour. Agent-based modelling aims to tackle this problem, offering a framework in which to simulate such systems and explore cellular design rules. In this article, I review the use of agent-based models in synthetic biology, outline the available computational tools, and provide details on recently engineered biological systems that are amenable to this approach. I further highlight the challenges facing this methodology and some of the potential future directions. © 2016 The Author(s).

Information processing in bacteria: memory, computation, and statistical physics: a key issues review

NASA Astrophysics Data System (ADS)

Lan, Ganhui; Tu, Yuhai

2016-05-01

Living systems have to constantly sense their external environment and adjust their internal state in order to survive and reproduce. Biological systems, from as complex as the brain to a single E. coli cell, have to process these data in order to make appropriate decisions. How do biological systems sense external signals? How do they process the information? How do they respond to signals? Through years of intense study by biologists, many key molecular players and their interactions have been identified in different biological machineries that carry out these signaling functions. However, an integrated, quantitative understanding of the whole system is still lacking for most cellular signaling pathways, not to say the more complicated neural circuits. To study signaling processes in biology, the key thing to measure is the input-output relationship. The input is the signal itself, such as chemical concentration, external temperature, light (intensity and frequency), and more complex signals such as the face of a cat. The output can be protein conformational changes and covalent modifications (phosphorylation, methylation, etc), gene expression, cell growth and motility, as well as more complex output such as neuron firing patterns and behaviors of higher animals. Due to the inherent noise in biological systems, the measured input-output dependence is often noisy. These noisy data can be analysed by using powerful tools and concepts from information theory such as mutual information, channel capacity, and the maximum entropy hypothesis. This information theory approach has been successfully used to reveal the underlying correlations between key components of biological networks, to set bounds for network performance, and to understand possible network architecture in generating observed correlations. Although the information theory approach provides a general tool in analysing noisy biological data and may be used to suggest possible network architectures in preserving information, it does not reveal the underlying mechanism that leads to the observed input-output relationship, nor does it tell us much about which information is important for the organism and how biological systems use information to carry out specific functions. To do that, we need to develop models of the biological machineries, e.g. biochemical networks and neural networks, to understand the dynamics of biological information processes. This is a much more difficult task. It requires deep knowledge of the underlying biological network—the main players (nodes) and their interactions (links)—in sufficient detail to build a model with predictive power, as well as quantitative input-output measurements of the system under different perturbations (both genetic variations and different external conditions) to test the model predictions to guide further development of the model. Due to the recent growth of biological knowledge thanks in part to high throughput methods (sequencing, gene expression microarray, etc) and development of quantitative in vivo techniques such as various florescence technology, these requirements are starting to be realized in different biological systems. The possible close interaction between quantitative experimentation and theoretical modeling has made systems biology an attractive field for physicists interested in quantitative biology. In this review, we describe some of the recent work in developing a quantitative predictive model of bacterial chemotaxis, which can be considered as the hydrogen atom of systems biology. Using statistical physics approaches, such as the Ising model and Langevin equation, we study how bacteria, such as E. coli, sense and amplify external signals, how they keep a working memory of the stimuli, and how they use these data to compute the chemical gradient. In particular, we will describe how E. coli cells avoid cross-talk in a heterogeneous receptor cluster to keep a ligand-specific memory. We will also study the thermodynamic costs of adaptation for cells to maintain an accurate memory. The statistical physics based approach described here should be useful in understanding design principles for cellular biochemical circuits in general.

Information processing in bacteria: memory, computation, and statistical physics: a key issues review.

PubMed

Lan, Ganhui; Tu, Yuhai

2016-05-01

Living systems have to constantly sense their external environment and adjust their internal state in order to survive and reproduce. Biological systems, from as complex as the brain to a single E. coli cell, have to process these data in order to make appropriate decisions. How do biological systems sense external signals? How do they process the information? How do they respond to signals? Through years of intense study by biologists, many key molecular players and their interactions have been identified in different biological machineries that carry out these signaling functions. However, an integrated, quantitative understanding of the whole system is still lacking for most cellular signaling pathways, not to say the more complicated neural circuits. To study signaling processes in biology, the key thing to measure is the input-output relationship. The input is the signal itself, such as chemical concentration, external temperature, light (intensity and frequency), and more complex signals such as the face of a cat. The output can be protein conformational changes and covalent modifications (phosphorylation, methylation, etc), gene expression, cell growth and motility, as well as more complex output such as neuron firing patterns and behaviors of higher animals. Due to the inherent noise in biological systems, the measured input-output dependence is often noisy. These noisy data can be analysed by using powerful tools and concepts from information theory such as mutual information, channel capacity, and the maximum entropy hypothesis. This information theory approach has been successfully used to reveal the underlying correlations between key components of biological networks, to set bounds for network performance, and to understand possible network architecture in generating observed correlations. Although the information theory approach provides a general tool in analysing noisy biological data and may be used to suggest possible network architectures in preserving information, it does not reveal the underlying mechanism that leads to the observed input-output relationship, nor does it tell us much about which information is important for the organism and how biological systems use information to carry out specific functions. To do that, we need to develop models of the biological machineries, e.g. biochemical networks and neural networks, to understand the dynamics of biological information processes. This is a much more difficult task. It requires deep knowledge of the underlying biological network-the main players (nodes) and their interactions (links)-in sufficient detail to build a model with predictive power, as well as quantitative input-output measurements of the system under different perturbations (both genetic variations and different external conditions) to test the model predictions to guide further development of the model. Due to the recent growth of biological knowledge thanks in part to high throughput methods (sequencing, gene expression microarray, etc) and development of quantitative in vivo techniques such as various florescence technology, these requirements are starting to be realized in different biological systems. The possible close interaction between quantitative experimentation and theoretical modeling has made systems biology an attractive field for physicists interested in quantitative biology. In this review, we describe some of the recent work in developing a quantitative predictive model of bacterial chemotaxis, which can be considered as the hydrogen atom of systems biology. Using statistical physics approaches, such as the Ising model and Langevin equation, we study how bacteria, such as E. coli, sense and amplify external signals, how they keep a working memory of the stimuli, and how they use these data to compute the chemical gradient. In particular, we will describe how E. coli cells avoid cross-talk in a heterogeneous receptor cluster to keep a ligand-specific memory. We will also study the thermodynamic costs of adaptation for cells to maintain an accurate memory. The statistical physics based approach described here should be useful in understanding design principles for cellular biochemical circuits in general.

Relations among Functional Systems in Behavior Analysis

PubMed Central

Thompson, Travis

2007-01-01

This paper proposes that an organism's integrated repertoire of operant behavior has the status of a biological system, similar to other biological systems, like the nervous, cardiovascular, or immune systems. Evidence from a number of sources indicates that the distinctions between biological and behavioral events is often misleading, engendering counterproductive explanatory controversy. A good deal of what is viewed as biological (often thought to be inaccessible or hypothetical) can become publicly measurable variables using currently available and developing technologies. Moreover, such endogenous variables can serve as establishing operations, discriminative stimuli, conjoint mediating events, and maintaining consequences within a functional analysis of behavior and need not lead to reductionistic explanation. I suggest that explanatory misunderstandings often arise from conflating different levels of analysis and that behavior analysis can extend its reach by identifying variables operating within a functional analysis that also serve functions in other biological systems. PMID:17575907

cellPACK: A Virtual Mesoscope to Model and Visualize Structural Systems Biology

PubMed Central

Johnson, Graham T.; Autin, Ludovic; Al-Alusi, Mostafa; Goodsell, David S.; Sanner, Michel F.; Olson, Arthur J.

2014-01-01

cellPACK assembles computational models of the biological mesoscale, an intermediate scale (10−7–10−8m) between molecular and cellular biology. cellPACK’s modular architecture unites existing and novel packing algorithms to generate, visualize and analyze comprehensive 3D models of complex biological environments that integrate data from multiple experimental systems biology and structural biology sources. cellPACK is currently available as open source code, with tools for validation of models and with recipes and models for five biological systems: blood plasma, cytoplasm, synaptic vesicles, HIV and a mycoplasma cell. We have applied cellPACK to model distributions of HIV envelope protein to test several hypotheses for consistency with experimental observations. Biologists, educators, and outreach specialists can interact with cellPACK models, develop new recipes and perform packing experiments through scripting and graphical user interfaces at http://cellPACK.org. PMID:25437435

Synthetic biology: tools to design microbes for the production of chemicals and fuels.

PubMed

Seo, Sang Woo; Yang, Jina; Min, Byung Eun; Jang, Sungho; Lim, Jae Hyung; Lim, Hyun Gyu; Kim, Seong Cheol; Kim, Se Yeon; Jeong, Jun Hong; Jung, Gyoo Yeol

2013-11-01

The engineering of biological systems to achieve specific purposes requires design tools that function in a predictable and quantitative manner. Recent advances in the field of synthetic biology, particularly in the programmable control of gene expression at multiple levels of regulation, have increased our ability to efficiently design and optimize biological systems to perform designed tasks. Furthermore, implementation of these designs in biological systems highlights the potential of using these tools to build microbial cell factories for the production of chemicals and fuels. In this paper, we review current developments in the design of tools for controlling gene expression at transcriptional, post-transcriptional and post-translational levels, and consider potential applications of these tools. Copyright © 2013 Elsevier Inc. All rights reserved.

Biomimetic chemical sensors using bioengineered olfactory and taste cells.

PubMed

Du, Liping; Zou, Ling; Zhao, Luhang; Wang, Ping; Wu, Chunsheng

2014-01-01

Biological olfactory and taste systems are natural chemical sensing systems with unique performances for the detection of environmental chemical signals. With the advances in olfactory and taste transduction mechanisms, biomimetic chemical sensors have achieved significant progress due to their promising prospects and potential applications. Biomimetic chemical sensors exploit the unique capability of biological functional components for chemical sensing, which are often sourced from sensing units of biological olfactory or taste systems at the tissue level, cellular level, or molecular level. Specifically, at the cellular level, there are mainly two categories of cells have been employed for the development of biomimetic chemical sensors, which are natural cells and bioengineered cells, respectively. Natural cells are directly isolated from biological olfactory and taste systems, which are convenient to achieve. However, natural cells often suffer from the undefined sensing properties and limited amount of identical cells. On the other hand, bioengineered cells have shown decisive advantages to be applied in the development of biomimetic chemical sensors due to the powerful biotechnology for the reconstruction of the cell sensing properties. Here, we briefly summarized the most recent advances of biomimetic chemical sensors using bioengineered olfactory and taste cells. The development challenges and future trends are discussed as well.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogura, Toshihiko, E-mail: t-ogura@aist.go.jp

Scanning electron microscopy (SEM) has been widely used to examine biological specimens of bacteria, viruses and proteins. Until now, atmospheric and/or wet biological specimens have been examined using various atmospheric holders or special equipment involving SEM. Unfortunately, they undergo heavy radiation damage by the direct electron beam. In addition, images of unstained biological samples in water yield poor contrast. We recently developed a new analytical technology involving a frequency transmission electric-field (FTE) method based on thermionic SEM. This method is suitable for high-contrast imaging of unstained biological specimens. Our aim was to optimise the method. Here we describe a high-resolutionmore » FTE system based on field-emission SEM; it allows for imaging and nanoscale examination of various biological specimens in water without radiation damage. The spatial resolution is 8 nm, which is higher than 41 nm of the existing FTE system. Our new method can be easily utilised for examination of unstained biological specimens including bacteria, viruses and protein complexes. Furthermore, our high-resolution FTE system can be used for diverse liquid samples across a broad range of scientific fields, e.g. nanoparticles, nanotubes and organic and catalytic materials. - Highlights: • We developed a high-resolution frequency transmission electric-field (FTE) system. • High-resolution FTE system is introduced in the field-emission SEM. • The spatial resolution of high-resolution FTE method is 8 nm. • High-resolution FTE system enables observation of the intact IgM particles in water.« less

75 FR 35492 - Guidance for Industry on Lupus Nephritis Caused By Systemic Lupus Erythematosus-Developing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-22

...] Guidance for Industry on Lupus Nephritis Caused By Systemic Lupus Erythematosus--Developing Medical... entitled ``Lupus Nephritis Caused By Systemic Lupus Erythematosus--Developing Medical Products for... biological products, and medical devices for the treatment of lupus nephritis (LN) caused by systemic lupus...

Towards Engineering Biological Systems in a Broader Context.

PubMed

Venturelli, Ophelia S; Egbert, Robert G; Arkin, Adam P

2016-02-27

Significant advances have been made in synthetic biology to program information processing capabilities in cells. While these designs can function predictably in controlled laboratory environments, the reliability of these devices in complex, temporally changing environments has not yet been characterized. As human society faces global challenges in agriculture, human health and energy, synthetic biology should develop predictive design principles for biological systems operating in complex environments. Natural biological systems have evolved mechanisms to overcome innumerable and diverse environmental challenges. Evolutionary design rules should be extracted and adapted to engineer stable and predictable ecological function. We highlight examples of natural biological responses spanning the cellular, population and microbial community levels that show promise in synthetic biology contexts. We argue that synthetic circuits embedded in host organisms or designed ecologies informed by suitable measurement of biotic and abiotic environmental parameters could be used as engineering substrates to achieve target functions in complex environments. Successful implementation of these methods will broaden the context in which synthetic biological systems can be applied to solve important problems. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recent advances in systems metabolic engineering tools and strategies.

PubMed

Chae, Tong Un; Choi, So Young; Kim, Je Woong; Ko, Yoo-Sung; Lee, Sang Yup

2017-10-01

Metabolic engineering has been playing increasingly important roles in developing microbial cell factories for the production of various chemicals and materials to achieve sustainable chemical industry. Nowadays, many tools and strategies are available for performing systems metabolic engineering that allows systems-level metabolic engineering in more sophisticated and diverse ways by adopting rapidly advancing methodologies and tools of systems biology, synthetic biology and evolutionary engineering. As an outcome, development of more efficient microbial cell factories has become possible. Here, we review recent advances in systems metabolic engineering tools and strategies together with accompanying application examples. In addition, we describe how these tools and strategies work together in simultaneous and synergistic ways to develop novel microbial cell factories. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthetic Biology Outside the Cell: Linking Computational Tools to Cell-Free Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewis, Daniel D.; Department of Biomedical Engineering, University of California Davis, Davis, CA; Villarreal, Fernando D.

As mathematical models become more commonly integrated into the study of biology, a common language for describing biological processes is manifesting. Many tools have emerged for the simulation of in vivo synthetic biological systems, with only a few examples of prominent work done on predicting the dynamics of cell-free synthetic systems. At the same time, experimental biologists have begun to study dynamics of in vitro systems encapsulated by amphiphilic molecules, opening the door for the development of a new generation of biomimetic systems. In this review, we explore both in vivo and in vitro models of biochemical networks with amore » special focus on tools that could be applied to the construction of cell-free expression systems. We believe that quantitative studies of complex cellular mechanisms and pathways in synthetic systems can yield important insights into what makes cells different from conventional chemical systems.« less

Synthetic Biology Outside the Cell: Linking Computational Tools to Cell-Free Systems

PubMed Central

Lewis, Daniel D.; Villarreal, Fernando D.; Wu, Fan; Tan, Cheemeng

2014-01-01

As mathematical models become more commonly integrated into the study of biology, a common language for describing biological processes is manifesting. Many tools have emerged for the simulation of in vivo synthetic biological systems, with only a few examples of prominent work done on predicting the dynamics of cell-free synthetic systems. At the same time, experimental biologists have begun to study dynamics of in vitro systems encapsulated by amphiphilic molecules, opening the door for the development of a new generation of biomimetic systems. In this review, we explore both in vivo and in vitro models of biochemical networks with a special focus on tools that could be applied to the construction of cell-free expression systems. We believe that quantitative studies of complex cellular mechanisms and pathways in synthetic systems can yield important insights into what makes cells different from conventional chemical systems. PMID:25538941

Synthetic biology outside the cell: linking computational tools to cell-free systems.

PubMed

Lewis, Daniel D; Villarreal, Fernando D; Wu, Fan; Tan, Cheemeng

2014-01-01

As mathematical models become more commonly integrated into the study of biology, a common language for describing biological processes is manifesting. Many tools have emerged for the simulation of in vivo synthetic biological systems, with only a few examples of prominent work done on predicting the dynamics of cell-free synthetic systems. At the same time, experimental biologists have begun to study dynamics of in vitro systems encapsulated by amphiphilic molecules, opening the door for the development of a new generation of biomimetic systems. In this review, we explore both in vivo and in vitro models of biochemical networks with a special focus on tools that could be applied to the construction of cell-free expression systems. We believe that quantitative studies of complex cellular mechanisms and pathways in synthetic systems can yield important insights into what makes cells different from conventional chemical systems.

Managing biological networks by using text mining and computer-aided curation

NASA Astrophysics Data System (ADS)

Yu, Seok Jong; Cho, Yongseong; Lee, Min-Ho; Lim, Jongtae; Yoo, Jaesoo

2015-11-01

In order to understand a biological mechanism in a cell, a researcher should collect a huge number of protein interactions with experimental data from experiments and the literature. Text mining systems that extract biological interactions from papers have been used to construct biological networks for a few decades. Even though the text mining of literature is necessary to construct a biological network, few systems with a text mining tool are available for biologists who want to construct their own biological networks. We have developed a biological network construction system called BioKnowledge Viewer that can generate a biological interaction network by using a text mining tool and biological taggers. It also Boolean simulation software to provide a biological modeling system to simulate the model that is made with the text mining tool. A user can download PubMed articles and construct a biological network by using the Multi-level Knowledge Emergence Model (KMEM), MetaMap, and A Biomedical Named Entity Recognizer (ABNER) as a text mining tool. To evaluate the system, we constructed an aging-related biological network that consist 9,415 nodes (genes) by using manual curation. With network analysis, we found that several genes, including JNK, AP-1, and BCL-2, were highly related in aging biological network. We provide a semi-automatic curation environment so that users can obtain a graph database for managing text mining results that are generated in the server system and can navigate the network with BioKnowledge Viewer, which is freely available at http://bioknowledgeviewer.kisti.re.kr.

Eric P. Knoshaug | NREL

Science.gov Websites

P. Knoshaug Photo of Eric P. Knoshaug Eric Knoshaug Researcher IV-Molecular Biology Eric.Knoshaug , molecular biology, and microbial physiology Fermentation and growth systems development Metabolic

Proposal for the development of biologics in pediatric rheumatology.

PubMed

Mori, Masaaki; Nakagawa, Masao; Tsuchida, Nao; Kawada, Kou; Sato, Junko; Sakiyama, Michiyo; Hirano, Shinya; Sato, Katsuaki; Nakamura, Hidefumi

2018-02-01

In order to assess the development, approval and early introduction into clinical practice of biologics in the pediatric field, we herein describe the current status of the development to approval of biologics as anti-rheumatic agents for children in Japan, discuss the present problems and provide a proposal for the future. It has become apparent that the duration of the review period required for the preparation of clinical trials and Pharmaceuticals and Medical Devices Agency approval is clearly reduced compared with the past. Thus, it was speculated that a rate-limiting step in the process from development to approval was the duration of clinical trials from start to end. Hence, we focused on the following key words with regard to promotion of the development of biologics and their early practical use: "registry", "centralization", and "global cooperation", all of which are related to the reduction of duration of a clinical trial. In conclusion, to reduce the duration of a clinical trial, it is essential to complete a world-scale registry system by developing the registry system established by the Pediatric Rheumatology Association of Japan. The next step is then to carefully plan to participate in the international network using the world-scale registry system, and develop global cooperative trials in which we can ensure a sufficient number of entries from Japan. © 2017 Japan Pediatric Society.

Evolutionary game based control for biological systems with applications in drug delivery.

PubMed

Li, Xiaobo; Lenaghan, Scott C; Zhang, Mingjun

2013-06-07

Control engineering and analysis of biological systems have become increasingly important for systems and synthetic biology. Unfortunately, no widely accepted control framework is currently available for these systems, especially at the cell and molecular levels. This is partially due to the lack of appropriate mathematical models to describe the unique dynamics of biological systems, and the lack of implementation techniques, such as ultra-fast and ultra-small devices and corresponding control algorithms. This paper proposes a control framework for biological systems subject to dynamics that exhibit adaptive behavior under evolutionary pressures. The control framework was formulated based on evolutionary game based modeling, which integrates both the internal dynamics and the population dynamics. In the proposed control framework, the adaptive behavior was characterized as an internal dynamic, and the external environment was regarded as an external control input. The proposed open-interface control framework can be integrated with additional control algorithms for control of biological systems. To demonstrate the effectiveness of the proposed framework, an optimal control strategy was developed and validated for drug delivery using the pathogen Giardia lamblia as a test case. In principle, the proposed control framework can be applied to any biological system exhibiting adaptive behavior under evolutionary pressures. Copyright © 2013 Elsevier Ltd. All rights reserved.

Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.

The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhancedmore » approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures to each infectious condition. Through this DBN computational approach, the method identified significantly perturbed pathways and GO category groups of genes that define the pathogenicity signatures of the infectious agent. Our preliminary results provide deeper understanding of the overall complexity of host innate immune response as well as the identification of host gene perturbations that defines a unique host temporal biosignature response to each pathogen. The application of advanced computational methods for developing interactome models based on DBNs has proven to be instrumental in elucidating novel host responses and improved functional biological insight into the host defensive mechanisms. Evaluating the unique differences in pathway and GO perturbations across pathogen conditions allowed the identification of plausible host pathogen interaction mechanisms. Accordingly, a systems biology approach to study molecular pathway gene expression profiles of host cellular responses to microbial pathogens holds great promise as a methodology to identify, model and predict the overall dynamics of the host pathogen interactome. Thus, we propose that such an approach has immediate application to the rational design of brucellosis and salmonellosis vaccines.« less

Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: linking systems biology with vaccine development.

PubMed

Adams, L Garry; Khare, Sangeeta; Lawhon, Sara D; Rossetti, Carlos A; Lewin, Harris A; Lipton, Mary S; Turse, Joshua E; Wylie, Dennis C; Bai, Yu; Drake, Kenneth L

2011-09-22

The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host-pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic ΔsipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures to each infectious condition. Through this DBN computational approach, the method identified significantly perturbed pathways and GO category groups of genes that define the pathogenicity signatures of the infectious agent. Our preliminary results provide deeper understanding of the overall complexity of host innate immune response as well as the identification of host gene perturbations that defines a unique host temporal biosignature response to each pathogen. The application of advanced computational methods for developing interactome models based on DBNs has proven to be instrumental in elucidating novel host responses and improved functional biological insight into the host defensive mechanisms. Evaluating the unique differences in pathway and GO perturbations across pathogen conditions allowed the identification of plausible host-pathogen interaction mechanisms. Accordingly, a systems biology approach to study molecular pathway gene expression profiles of host cellular responses to microbial pathogens holds great promise as a methodology to identify, model and predict the overall dynamics of the host-pathogen interactome. Thus, we propose that such an approach has immediate application to the rational design of brucellosis and salmonellosis vaccines. Copyright © 2011 Elsevier Ltd. All rights reserved.

Revisiting lab-on-a-chip technology for drug discovery.

PubMed

Neuži, Pavel; Giselbrecht, Stefan; Länge, Kerstin; Huang, Tony Jun; Manz, Andreas

2012-08-01

The field of microfluidics or lab-on-a-chip technology aims to improve and extend the possibilities of bioassays, cell biology and biomedical research based on the idea of miniaturization. Microfluidic systems allow more accurate modelling of physiological situations for both fundamental research and drug development, and enable systematic high-volume testing for various aspects of drug discovery. Microfluidic systems are in development that not only model biological environments but also physically mimic biological tissues and organs; such 'organs on a chip' could have an important role in expediting early stages of drug discovery and help reduce reliance on animal testing. This Review highlights the latest lab-on-a-chip technologies for drug discovery and discusses the potential for future developments in this field.

Network analysis reveals stage-specific changes in zebrafish embryo development using time course whole transcriptome profiling and prior biological knowledge.

PubMed

Zhang, Yuji

2015-01-01

Molecular networks act as the backbone of molecular activities within cells, offering a unique opportunity to better understand the mechanism of diseases. While network data usually constitute only static network maps, integrating them with time course gene expression information can provide clues to the dynamic features of these networks and unravel the mechanistic driver genes characterizing cellular responses. Time course gene expression data allow us to broadly "watch" the dynamics of the system. However, one challenge in the analysis of such data is to establish and characterize the interplay among genes that are altered at different time points in the context of a biological process or functional category. Integrative analysis of these data sources will lead us a more complete understanding of how biological entities (e.g., genes and proteins) coordinately perform their biological functions in biological systems. In this paper, we introduced a novel network-based approach to extract functional knowledge from time-dependent biological processes at a system level using time course mRNA sequencing data in zebrafish embryo development. The proposed method was applied to investigate 1α, 25(OH)2D3-altered mechanisms in zebrafish embryo development. We applied the proposed method to a public zebrafish time course mRNA-Seq dataset, containing two different treatments along four time points. We constructed networks between gene ontology biological process categories, which were enriched in differential expressed genes between consecutive time points and different conditions. The temporal propagation of 1α, 25-Dihydroxyvitamin D3-altered transcriptional changes started from a few genes that were altered initially at earlier stage, to large groups of biological coherent genes at later stages. The most notable biological processes included neuronal and retinal development and generalized stress response. In addition, we also investigated the relationship among biological processes enriched in co-expressed genes under different conditions. The enriched biological processes include translation elongation, nucleosome assembly, and retina development. These network dynamics provide new insights into the impact of 1α, 25-Dihydroxyvitamin D3 treatment in bone and cartilage development. We developed a network-based approach to analyzing the DEGs at different time points by integrating molecular interactions and gene ontology information. These results demonstrate that the proposed approach can provide insight on the molecular mechanisms taking place in vertebrate embryo development upon treatment with 1α, 25(OH)2D3. Our approach enables the monitoring of biological processes that can serve as a basis for generating new testable hypotheses. Such network-based integration approach can be easily extended to any temporal- or condition-dependent genomic data analyses.

Economic development and conservation of biological and cultural diversity in Yunnan Province, China

USGS Publications Warehouse

Stendell, R.C.; Johnson, Richard L.; Mosesso, J.P.; Zhang, X.

2001-01-01

Chinese and American scientists are co-operating to develop concepts, strategies, agreements, and proposals in support of an economic development and sustainable ecosystems project in Yunnan Province, People's Republic of China. Yunnan's Provincial Government has initiated a major programme to develop and further utilise its biological resources to help improve economic conditions for its citizens. They are co-operating with the US Geological Survey (USGS) on evaluation and management of biological resources so economic development will be compatible with sustainable ecological systems. Scientists from the USGS and co-operating universities will provide expertise on synthesising biological data, conducting a Gap Analysis for the Province, evaluating innovative economic opportunities, and designing an effective education, training, and outreach programme.

Biomimetic machine vision system.

PubMed

Harman, William M; Barrett, Steven F; Wright, Cameron H G; Wilcox, Michael

2005-01-01

Real-time application of digital imaging for use in machine vision systems has proven to be prohibitive when used within control systems that employ low-power single processors without compromising the scope of vision or resolution of captured images. Development of a real-time machine analog vision system is the focus of research taking place at the University of Wyoming. This new vision system is based upon the biological vision system of the common house fly. Development of a single sensor is accomplished, representing a single facet of the fly's eye. This new sensor is then incorporated into an array of sensors capable of detecting objects and tracking motion in 2-D space. This system "preprocesses" incoming image data resulting in minimal data processing to determine the location of a target object. Due to the nature of the sensors in the array, hyperacuity is achieved thereby eliminating resolutions issues found in digital vision systems. In this paper, we will discuss the biological traits of the fly eye and the specific traits that led to the development of this machine vision system. We will also discuss the process of developing an analog based sensor that mimics the characteristics of interest in the biological vision system. This paper will conclude with a discussion of how an array of these sensors can be applied toward solving real-world machine vision issues.

On a biologically inspired topology optimization method

NASA Astrophysics Data System (ADS)

Kobayashi, Marcelo H.

2010-03-01

This work concerns the development of a biologically inspired methodology for the study of topology optimization in engineering and natural systems. The methodology is based on L systems and its turtle interpretation for the genotype-phenotype modeling of the topology development. The topology is analyzed using the finite element method, and optimized using an evolutionary algorithm with the genetic encoding of the L system and its turtle interpretation, as well as, body shape and physical characteristics. The test cases considered in this work clearly show the suitability of the proposed method for the study of engineering and natural complex systems.

Bioseguridad in Mexico: Pursuing Security between Local and Global Biologies.

PubMed

Wanderer, Emily Mannix

2017-09-01

In the aftermath of the 2009 outbreak of H1N1 influenza, scientists in Mexico sought to develop bioseguridad, that is, to protect biological life in Mexico by safely conducting research on infectious disease. Drawing on ethnographic research in laboratories and with scientists in Mexico, I look at how scientists make claims about local differences in regulations, infrastructure, bodies, and culture. The scientists working with infectious microbes sought to establish how different microbial ecologies, human immune systems, and political and regulatory systems made the risks of research different in Mexico from other countries. In developing bioseguridad, the idea of globalized biology that animates many public health projects was undermined as scientists attended to the elements of place that affected human health and safety. Scientists argued for the importance of local biologies, generating tension with global public health projects and regulations premised on the universality of biology. © 2016 by the American Anthropological Association.

Nanoscale hybrid systems based on carbon nanotubes for biological sensing and control

PubMed Central

Cho, Youngtak; Shin, Narae; Kim, Daesan; Park, Jae Yeol

2017-01-01

This paper provides a concise review on the recent development of nanoscale hybrid systems based on carbon nanotubes (CNTs) for biological sensing and control. CNT-based hybrid systems have been intensively studied for versatile applications of biological interfaces such as sensing, cell therapy and tissue regeneration. Recent advances in nanobiotechnology not only enable the fabrication of highly sensitive biosensors at nanoscale but also allow the applications in the controls of cell growth and differentiation. This review describes the fabrication methods of such CNT-based hybrid systems and their applications in biosensing and cell controls. PMID:28188158

High definition for systems biology of microbial communities: metagenomics gets genome-centric and strain-resolved.

PubMed

Turaev, Dmitrij; Rattei, Thomas

2016-06-01

The systems biology of microbial communities, organismal communities inhabiting all ecological niches on earth, has in recent years been strongly facilitated by the rapid development of experimental, sequencing and data analysis methods. Novel experimental approaches and binning methods in metagenomics render the semi-automatic reconstructions of near-complete genomes of uncultivable bacteria possible, while advances in high-resolution amplicon analysis allow for efficient and less biased taxonomic community characterization. This will also facilitate predictive modeling approaches, hitherto limited by the low resolution of metagenomic data. In this review, we pinpoint the most promising current developments in metagenomics. They facilitate microbial systems biology towards a systemic understanding of mechanisms in microbial communities with scopes of application in many areas of our daily life. Copyright © 2016 Elsevier Ltd. All rights reserved.

ACToR A Aggregated Computational Toxicology Resource ...

EPA Pesticide Factsheets

We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology. We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology.

ACToR A Aggregated Computational Toxicology Resource (S) ...

EPA Pesticide Factsheets

We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology. We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology.

Federal Research and Development Funding: FY2010

DTIC Science & Technology

2009-09-23

Budget activities 6.4 and 6.5 focus on the development of specific weapon systems or components (e.g., the Joint Strike Fighter or missile defense systems...more than the request for chemical and biological basic research and would provide $10 million in the Infrastructure and Geophysical Division for...40 40 Chemical and Biological 208 200 207 222 207 Command, Control, and Interoperability 57 75 80 81 83 Explosives 78 96 121 121 121 Human

Federal Research and Development Funding: FY2010

DTIC Science & Technology

2009-11-23

represent the more research-oriented part of the RDT&E program. Budget activities 6.4 and 6.5 focus on the development of specific weapon systems or...to fund developmental testing of the BioWatch Generation 3 biological agent detection system. The Administration requested these funds for the...Acquisition, and Operations 800 826 825 844 856 Border and Maritime 33 40 40 40 44 Chemical and Biological 200 207 222 207 207 Command, Control, and

ENFIN--A European network for integrative systems biology.

PubMed

Kahlem, Pascal; Clegg, Andrew; Reisinger, Florian; Xenarios, Ioannis; Hermjakob, Henning; Orengo, Christine; Birney, Ewan

2009-11-01

Integration of biological data of various types and the development of adapted bioinformatics tools represent critical objectives to enable research at the systems level. The European Network of Excellence ENFIN is engaged in developing an adapted infrastructure to connect databases, and platforms to enable both the generation of new bioinformatics tools and the experimental validation of computational predictions. With the aim of bridging the gap existing between standard wet laboratories and bioinformatics, the ENFIN Network runs integrative research projects to bring the latest computational techniques to bear directly on questions dedicated to systems biology in the wet laboratory environment. The Network maintains internally close collaboration between experimental and computational research, enabling a permanent cycling of experimental validation and improvement of computational prediction methods. The computational work includes the development of a database infrastructure (EnCORE), bioinformatics analysis methods and a novel platform for protein function analysis FuncNet.

Extending and expanding the Darwinian synthesis: the role of complex systems dynamics.

PubMed

Weber, Bruce H

2011-03-01

Darwinism is defined here as an evolving research tradition based upon the concepts of natural selection acting upon heritable variation articulated via background assumptions about systems dynamics. Darwin's theory of evolution was developed within a context of the background assumptions of Newtonian systems dynamics. The Modern Evolutionary Synthesis, or neo-Darwinism, successfully joined Darwinian selection and Mendelian genetics by developing population genetics informed by background assumptions of Boltzmannian systems dynamics. Currently the Darwinian Research Tradition is changing as it incorporates new information and ideas from molecular biology, paleontology, developmental biology, and systems ecology. This putative expanded and extended synthesis is most perspicuously deployed using background assumptions from complex systems dynamics. Such attempts seek to not only broaden the range of phenomena encompassed by the Darwinian Research Tradition, such as neutral molecular evolution, punctuated equilibrium, as well as developmental biology, and systems ecology more generally, but to also address issues of the emergence of evolutionary novelties as well as of life itself. Copyright © 2010 Elsevier Ltd. All rights reserved.

Supplementing Introductory Biology with On-Line Curriculum

ERIC Educational Resources Information Center

McGroarty, Estelle; Parker, Joyce; Heidemann, Merle; Lim, Heejun; Olson, Mark; Long, Tammy; Merrill, John; Riffell, Samuel; Smith, James; Batzli, Janet; Kirschtel, David

2004-01-01

We developed web-based modules addressing fundamental concepts of introductory biology delivered through the LON-CAPA course management system. These modules were designed and used to supplement large, lecture-based introductory biology classes. Incorporating educational principles and the strength of web-based instructional technology, choices…

Modeling biochemical transformation processes and information processing with Narrator.

PubMed

Mandel, Johannes J; Fuss, Hendrik; Palfreyman, Niall M; Dubitzky, Werner

2007-03-27

Software tools that model and simulate the dynamics of biological processes and systems are becoming increasingly important. Some of these tools offer sophisticated graphical user interfaces (GUIs), which greatly enhance their acceptance by users. Such GUIs are based on symbolic or graphical notations used to describe, interact and communicate the developed models. Typically, these graphical notations are geared towards conventional biochemical pathway diagrams. They permit the user to represent the transport and transformation of chemical species and to define inhibitory and stimulatory dependencies. A critical weakness of existing tools is their lack of supporting an integrative representation of transport, transformation as well as biological information processing. Narrator is a software tool facilitating the development and simulation of biological systems as Co-dependence models. The Co-dependence Methodology complements the representation of species transport and transformation together with an explicit mechanism to express biological information processing. Thus, Co-dependence models explicitly capture, for instance, signal processing structures and the influence of exogenous factors or events affecting certain parts of a biological system or process. This combined set of features provides the system biologist with a powerful tool to describe and explore the dynamics of life phenomena. Narrator's GUI is based on an expressive graphical notation which forms an integral part of the Co-dependence Methodology. Behind the user-friendly GUI, Narrator hides a flexible feature which makes it relatively easy to map models defined via the graphical notation to mathematical formalisms and languages such as ordinary differential equations, the Systems Biology Markup Language or Gillespie's direct method. This powerful feature facilitates reuse, interoperability and conceptual model development. Narrator is a flexible and intuitive systems biology tool. It is specifically intended for users aiming to construct and simulate dynamic models of biology without recourse to extensive mathematical detail. Its design facilitates mappings to different formal languages and frameworks. The combined set of features makes Narrator unique among tools of its kind. Narrator is implemented as Java software program and available as open-source from http://www.narrator-tool.org.

Modeling biochemical transformation processes and information processing with Narrator

PubMed Central

Mandel, Johannes J; Fuß, Hendrik; Palfreyman, Niall M; Dubitzky, Werner

2007-01-01

Background Software tools that model and simulate the dynamics of biological processes and systems are becoming increasingly important. Some of these tools offer sophisticated graphical user interfaces (GUIs), which greatly enhance their acceptance by users. Such GUIs are based on symbolic or graphical notations used to describe, interact and communicate the developed models. Typically, these graphical notations are geared towards conventional biochemical pathway diagrams. They permit the user to represent the transport and transformation of chemical species and to define inhibitory and stimulatory dependencies. A critical weakness of existing tools is their lack of supporting an integrative representation of transport, transformation as well as biological information processing. Results Narrator is a software tool facilitating the development and simulation of biological systems as Co-dependence models. The Co-dependence Methodology complements the representation of species transport and transformation together with an explicit mechanism to express biological information processing. Thus, Co-dependence models explicitly capture, for instance, signal processing structures and the influence of exogenous factors or events affecting certain parts of a biological system or process. This combined set of features provides the system biologist with a powerful tool to describe and explore the dynamics of life phenomena. Narrator's GUI is based on an expressive graphical notation which forms an integral part of the Co-dependence Methodology. Behind the user-friendly GUI, Narrator hides a flexible feature which makes it relatively easy to map models defined via the graphical notation to mathematical formalisms and languages such as ordinary differential equations, the Systems Biology Markup Language or Gillespie's direct method. This powerful feature facilitates reuse, interoperability and conceptual model development. Conclusion Narrator is a flexible and intuitive systems biology tool. It is specifically intended for users aiming to construct and simulate dynamic models of biology without recourse to extensive mathematical detail. Its design facilitates mappings to different formal languages and frameworks. The combined set of features makes Narrator unique among tools of its kind. Narrator is implemented as Java software program and available as open-source from . PMID:17389034

Construction of a Linux based chemical and biological information system.

PubMed

Molnár, László; Vágó, István; Fehér, András

2003-01-01

A chemical and biological information system with a Web-based easy-to-use interface and corresponding databases has been developed. The constructed system incorporates all chemical, numerical and textual data related to the chemical compounds, including numerical biological screen results. Users can search the database by traditional textual/numerical and/or substructure or similarity queries through the web interface. To build our chemical database management system, we utilized existing IT components such as ORACLE or Tripos SYBYL for database management and Zope application server for the web interface. We chose Linux as the main platform, however, almost every component can be used under various operating systems.

Promoting Systems Thinking through Biology Lessons

ERIC Educational Resources Information Center

Riess, Werner; Mischo, Christoph

2010-01-01

This study's goal was to analyze various teaching approaches within the context of natural science lessons, especially in biology. The main focus of the paper lies on the effectiveness of different teaching methods in promoting systems thinking in the field of Education for Sustainable Development. The following methods were incorporated into the…

Studies on Semantic Systems Chemical Biology

ERIC Educational Resources Information Center

Chen, Bin

2012-01-01

Current "one disease, one target and one drug" drug development paradigm is under question as relatively few drugs have reached the market in the last two decades. Increasingly research focus is being placed on the study of drug action against biological systems as a whole rather than against a single component (called "Systems…

Biological sample evaluation using a line-scan based SWIR hyperspectral imaging system

USDA-ARS?s Scientific Manuscript database

A new line-scan hyperspectral imaging system was developed to enable short wavelength infrared (SWIR) imagery for biological sample evaluation. Critical sensing components include a SWIR imaging spectrograph and an HgCdTe (MCT) focal plane array detector. To date, agricultural applications of infra...

The development of synthetic biology: a patent analysis.

PubMed

van Doren, Davy; Koenigstein, Stefan; Reiss, Thomas

2013-12-01

In the past decades, synthetic biology has gained interest regarding research and development efforts within the biotechnology domain. However, it is unclear to what extent synthetic biology has matured already into being commercially exploitable. By means of a patent analysis, this study shows that there is an increasing trend regarding synthetic biology related patent applications. The majority of retrieved patents relates to innovations facilitating the realisation of synthetic biology through improved understanding of biological systems. In addition, there is increased activity concerning the development of synthetic biology based applications. When looking at potential application areas, the majority of synthetic biology patents seems most relevant for the medical, energy and industrial sector. Furthermore, the analysis shows that most activity has been carried out by the USA, with Japan and a number of European countries considerably trailing behind. In addition, both universities and companies are major patent applicant actor types. The results presented here form a starting point for follow-up studies concerning the identification of drivers explaining the observed patent application trends in synthetic biology.

[THE INCONSISTENCIES OF REGULATION OF METABOLISM IN PHYLOGENESIS AT THREE LEVELS OF "RELATIVE BIOLOGICAL PERFECTION": ETIOLOGY OF METABOLIC PANDEMICS].

PubMed

Titov, V N

2015-11-01

The regulation of metabolism in vivo can be comprehended by considering stages of becoming inphylogenesis of humoral, hormonal, vegetative regulators separately: at the level of cells; in paracrin-regulated cenosises of cells; organs and systems under open blood circulation and closed system of blood flow. The levels of regulations formed at different stages of phylogenesis. Their completion occurred at achievement of "relative biological perfection". Only this way need of cells in functional, structural interaction and forming of multicellular developed. The development of organs and systems of organs also completed at the level of "relative biological perfection". From the same level the third stage of becoming of regulation of metabolism at the level of organism started. When three conditions of "relative biological perfection" achieved consequently at level in vivo are considered in species Homo sapiens using system approach it is detected that "relative biological perfection" in vivo is accompanied by different inconsistencies of regulation of metabolism. They are etiologic factors of "metabolic pandemics ". The inconsistencies (etiological factors) are consider as exemplified by local (at the level of paracrin-regulated cenosises of cells) and system (at the level of organism) regulation of biological reaction metabolism-microcirculation that results in dysfunction of target organs and development of pathogenesis of essential metabolic arterial hypertension. The article describes phylogenetic difference between visceral fatty cells and adpocytes, regulation of metabolism by phylogenetically late insulin, reaction of albumin at increasing of content of unesterified fatty acids in blood plasma, difference of function of resident macrophage and monocytes-macrophages in pathogenesis of atherosclerosis, metabolic syndrome, insulin resistance, obesity, under diabetes mellitus and essential metabolic arterial hypertension.

Engineering of microorganisms for the production of biofuels and perspectives based on systems metabolic engineering approaches.

PubMed

Jang, Yu-Sin; Park, Jong Myoung; Choi, Sol; Choi, Yong Jun; Seung, Do Young; Cho, Jung Hee; Lee, Sang Yup

2012-01-01

The increasing oil price and environmental concerns caused by the use of fossil fuel have renewed our interest in utilizing biomass as a sustainable resource for the production of biofuel. It is however essential to develop high performance microbes that are capable of producing biofuels with very high efficiency in order to compete with the fossil fuel. Recently, the strategies for developing microbial strains by systems metabolic engineering, which can be considered as metabolic engineering integrated with systems biology and synthetic biology, have been developed. Systems metabolic engineering allows successful development of microbes that are capable of producing several different biofuels including bioethanol, biobutanol, alkane, and biodiesel, and even hydrogen. In this review, the approaches employed to develop efficient biofuel producers by metabolic engineering and systems metabolic engineering approaches are reviewed with relevant example cases. It is expected that systems metabolic engineering will be employed as an essential strategy for the development of microbial strains for industrial applications. Copyright © 2011 Elsevier Inc. All rights reserved.

Mass balances for a biological life support system simulation model

NASA Technical Reports Server (NTRS)

Volk, Tyler; Rumel, John D.

1987-01-01

Design decisions to aid the development of future space-based biological life support systems (BLSS) can be made with simulation models. Here the biochemical stoichiometry is developed for: (1) protein, carbohydrate, fat, fiber, and lignin production in the edible and inedible parts of plants; (2) food consumption and production of organic solids in urine, feces, and wash water by the humans; and (3) operation of the waste processor. Flux values for all components are derived for a steady-state system with wheat as the sole food source.

How to integrate biological research into society and exclude errors in biomedical publications? Progress in theoretical and systems biology releases pressure on experimental research.

PubMed

Volkov, Vadim

2014-01-01

This brief opinion proposes measures to increase efficiency and exclude errors in biomedical research under the existing dynamic situation. Rapid changes in biology began with the description of the three dimensional structure of DNA 60 years ago; today biology has progressed by interacting with computer science and nanoscience together with the introduction of robotic stations for the acquisition of large-scale arrays of data. These changes have had an increasing influence on the entire research and scientific community. Future advance demands short-term measures to ensure error-proof and efficient development. They can include the fast publishing of negative results, publishing detailed methodical papers and excluding a strict connection between career progression and publication activity, especially for younger researchers. Further development of theoretical and systems biology together with the use of multiple experimental methods for biological experiments could also be helpful in the context of years and decades. With regards to the links between science and society, it is reasonable to compare both these systems, to find and describe specific features for biology and to integrate it into the existing stream of social life and financial fluxes. It will increase the level of scientific research and have mutual positive effects for both biology and society. Several examples are given for further discussion.

Extended Kalman Filter for Estimation of Parameters in Nonlinear State-Space Models of Biochemical Networks

PubMed Central

Sun, Xiaodian; Jin, Li; Xiong, Momiao

2008-01-01

It is system dynamics that determines the function of cells, tissues and organisms. To develop mathematical models and estimate their parameters are an essential issue for studying dynamic behaviors of biological systems which include metabolic networks, genetic regulatory networks and signal transduction pathways, under perturbation of external stimuli. In general, biological dynamic systems are partially observed. Therefore, a natural way to model dynamic biological systems is to employ nonlinear state-space equations. Although statistical methods for parameter estimation of linear models in biological dynamic systems have been developed intensively in the recent years, the estimation of both states and parameters of nonlinear dynamic systems remains a challenging task. In this report, we apply extended Kalman Filter (EKF) to the estimation of both states and parameters of nonlinear state-space models. To evaluate the performance of the EKF for parameter estimation, we apply the EKF to a simulation dataset and two real datasets: JAK-STAT signal transduction pathway and Ras/Raf/MEK/ERK signaling transduction pathways datasets. The preliminary results show that EKF can accurately estimate the parameters and predict states in nonlinear state-space equations for modeling dynamic biochemical networks. PMID:19018286

Synthetic Biology Open Language (SBOL) Version 2.2.0.

PubMed

Cox, Robert Sidney; Madsen, Curtis; McLaughlin, James Alastair; Nguyen, Tramy; Roehner, Nicholas; Bartley, Bryan; Beal, Jacob; Bissell, Michael; Choi, Kiri; Clancy, Kevin; Grünberg, Raik; Macklin, Chris; Misirli, Goksel; Oberortner, Ernst; Pocock, Matthew; Samineni, Meher; Zhang, Michael; Zhang, Zhen; Zundel, Zach; Gennari, John H; Myers, Chris; Sauro, Herbert; Wipat, Anil

2018-04-02

Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The synthetic biology open language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.2.0 of SBOL that builds upon version 2.1.0 published in last year's JIB special issue. In particular, SBOL 2.2.0 includes improved description and validation rules for genetic design provenance, an extension to support combinatorial genetic designs, a new class to add non-SBOL data as attachments, a new class for genetic design implementations, and a description of a methodology to describe the entire design-build-test-learn cycle within the SBOL data model.

Synthetic Biology Open Language (SBOL) Version 2.1.0.

PubMed

Beal, Jacob; Cox, Robert Sidney; Grünberg, Raik; McLaughlin, James; Nguyen, Tramy; Bartley, Bryan; Bissell, Michael; Choi, Kiri; Clancy, Kevin; Macklin, Chris; Madsen, Curtis; Misirli, Goksel; Oberortner, Ernst; Pocock, Matthew; Roehner, Nicholas; Samineni, Meher; Zhang, Michael; Zhang, Zhen; Zundel, Zach; Gennari, John H; Myers, Chris; Sauro, Herbert; Wipat, Anil

2016-09-01

Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The Synthetic Biology Open Language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.1 of SBOL that builds upon version 2.0 published in last year's JIB special issue. In particular, SBOL 2.1 includes improved rules for what constitutes a valid SBOL document, new role fields to simplify the expression of sequence features and how components are used in context, and new best practices descriptions to improve the exchange of basic sequence topology information and the description of genetic design provenance, as well as miscellaneous other minor improvements.

Synthetic Biology Open Language (SBOL) Version 2.1.0.

PubMed

Beal, Jacob; Cox, Robert Sidney; Grünberg, Raik; McLaughlin, James; Nguyen, Tramy; Bartley, Bryan; Bissell, Michael; Choi, Kiri; Clancy, Kevin; Macklin, Chris; Madsen, Curtis; Misirli, Goksel; Oberortner, Ernst; Pocock, Matthew; Roehner, Nicholas; Samineni, Meher; Zhang, Michael; Zhang, Zhen; Zundel, Zach; Gennari, John; Myers, Chris; Sauro, Herbert; Wipat, Anil

2016-12-18

Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The Synthetic Biology Open Language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.1 of SBOL that builds upon version 2.0 published in last year’s JIB special issue. In particular, SBOL 2.1 includes improved rules for what constitutes a valid SBOL document, new role fields to simplify the expression of sequence features and how components are used in context, and new best practices descriptions to improve the exchange of basic sequence topology information and the description of genetic design provenance, as well as miscellaneous other minor improvements.

Peptide and protein-based nanotubes for nanobiotechnology.

PubMed

Petrov, Anna; Audette, Gerald F

2012-01-01

The development of biologically relevant nanosystems such as biomolecular probes and sensors requires systems that effectively interface specific biochemical environments with abiotic architectures. The most widely studied nanomaterial, carbon nanotubes, has proven challenging in their adaptation for biomedical applications despite their numerous advantageous physical and electrochemical properties. On the other hand, development of bionanosystems through adaptation of existing biological systems has several advantages including their adaptability through modern recombinant DNA strategies. Indeed, the use of peptides, proteins and protein assemblies as nanotubes, scaffolds, and nanowires has shown much promise as a bottom-up approach to the development of novel bionanosystems. We highlight several unique peptide and protein systems that generate protein nanotubes (PNTs) that are being explored for the development of biosensors, probes, bionanowires, and drug delivery systems. Copyright © 2012 Wiley Periodicals, Inc.

Biological warfare agents

PubMed Central

Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

2010-01-01

The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies. PMID:21829313

Magnetic nanoparticles in different biological environments analyzed by magnetic particle spectroscopy

NASA Astrophysics Data System (ADS)

Löwa, Norbert; Seidel, Maria; Radon, Patricia; Wiekhorst, Frank

2017-04-01

Quantification of magnetic iron oxide nanoparticles (MNP) in biological systems like cells, tissue, or organs is of vital importance for development of novel biomedical applications, e.g. magnetofection, drug targeting or hyperthermia. Among others, the recently developed magnetic measurement technique magnetic particle spectroscopy (MPS) provides signals that are specific for MNP. MPS is based on the non-linear magnetic response of MNP exposed to a strong sinusoidal excitation field of up to 25 mT amplitude and 25 kHz frequency. So far, it has been proven a powerful tool for quantification of MNP in biological systems. In this study we investigated in detail the influence of typical biological media on the magnetic behavior of different MNP systems by MPS. The results reveal that amplitude and shape (ratio of harmonics) of the MPS spectra allow for perceptively monitoring changes in MNP magnetism caused by different physiological media. Additionally, the observed linear correlation between MPS amplitude and shape alterations can be used to reduce the quantification uncertainty for MNP suspended in a biological environment.

Mammalian Synthetic Biology: Engineering Biological Systems.

PubMed

Black, Joshua B; Perez-Pinera, Pablo; Gersbach, Charles A

2017-06-21

The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.

A versatile petri net based architecture for modeling and simulation of complex biological processes.

PubMed

Nagasaki, Masao; Doi, Atsushi; Matsuno, Hiroshi; Miyano, Satoru

2004-01-01

The research on modeling and simulation of complex biological systems is getting more important in Systems Biology. In this respect, we have developed Hybrid Function Petri net (HFPN) that was newly developed from existing Petri net because of their intuitive graphical representation and their capabilities for mathematical analyses. However, in the process of modeling metabolic, gene regulatory or signal transduction pathways with the architecture, we have realized three extensions of HFPN, (i) an entity should be extended to contain more than one value, (ii) an entity should be extended to handle other primitive types, e.g. boolean, string, (iii) an entity should be extended to handle more advanced type called object that consists of variables and methods, are necessary for modeling biological systems with Petri net based architecture. To deal with it, we define a new enhanced Petri net called hybrid functional Petri net with extension (HFPNe). To demonstrate the effectiveness of the enhancements, we model and simulate with HFPNe four biological processes that are diffcult to represent with the previous architecture HFPN.

NASA Space Biology Plant Research for 2010-2020

NASA Technical Reports Server (NTRS)

Levine, H. G.; Tomko, D. L.; Porterfield, D. M.

2012-01-01

The U.S. National Research Council (NRC) recently published "Recapturing a Future for Space Exploration: Life and Physical Sciences Research for a New Era" (http://www.nap.edu/catalog.php?record id=13048), and NASA completed a Space Biology Science Plan to develop a strategy for implementing its recommendations ( http://www.nasa.gov/exploration/library/esmd documents.html). The most important recommendations of the NRC report on plant biology in space were that NASA should: (1) investigate the roles of microbial-plant systems in long-term bioregenerative life support systems, and (2) establish a robust spaceflight program of research analyzing plant growth and physiological responses to the multiple stimuli encountered in spaceflight environments. These efforts should take advantage of recently emerged analytical technologies (genomics, transcriptomics, proteomics, metabolomics) and apply modern cellular and molecular approaches in the development of a vigorous flight-based and ground-based research program. This talk will describe NASA's strategy and plans for implementing these NRC Plant Space Biology recommendations. New research capabilities for Plant Biology, optimized by providing state-of-the-art automated technology and analytical techniques to maximize scientific return, will be described. Flight experiments will use the most appropriate platform to achieve science results (e.g., ISS, free flyers, sub-orbital flights) and NASA will work closely with its international partners and other U.S. agencies to achieve its objectives. One of NASA's highest priorities in Space Biology is the development research capabilities for use on the International Space Station and other flight platforms for studying multiple generations of large plants. NASA will issue recurring NASA Research Announcements (NRAs) that include a rapid turn-around model to more fully engage the biology community in designing experiments to respond to the NRC recommendations. In doing so, NASA's Space Biology research will optimize ISS research utilization, develop and demonstrate technology and hardware that will enable new science, and contribute to the base of fundamental knowledge that will facilitate development of new tools for human space exploration and Earth applications. By taking these steps, NASA will energize the Space Biology user community and advance our knowledge of the effect of the space flight environment on living systems.

Receptive fields and the theory of discriminant operators

NASA Astrophysics Data System (ADS)

Gupta, Madan M.; Hungenahally, Suresh K.

1991-02-01

Biological basis for machine vision is a notion which is being used extensively for the development of machine vision systems for various applications. In this paper we have made an attempt to emulate the receptive fields that exist in the biological visual channels. In particular we have exploited the notion of receptive fields for developing the mathematical functions named as discriminantfunctions for the extraction of transition information from signals and multi-dimensional signals and images. These functions are found to be useful for the development of artificial receptive fields for neuro-vision systems. 1.

Characterising the development of the understanding of human body systems in high-school biology students - a longitudinal study

NASA Astrophysics Data System (ADS)

Snapir, Zohar; Eberbach, Catherine; Ben-Zvi-Assaraf, Orit; Hmelo-Silver, Cindy; Tripto, Jaklin

2017-10-01

Science education today has become increasingly focused on research into complex natural, social and technological systems. In this study, we examined the development of high-school biology students' systems understanding of the human body, in a three-year longitudinal study. The development of the students' system understanding was evaluated using the Components Mechanisms Phenomena (CMP) framework for conceptual representation. We coded and analysed the repertory grid personal constructs of 67 high-school biology students at 4 points throughout the study. Our data analysis builds on the assumption that systems understanding entails a perception of all the system categories, including structures within the system (its Components), specific processes and interactions at the macro and micro levels (Mechanisms), and the Phenomena that present the macro scale of processes and patterns within a system. Our findings suggest that as the learning process progressed, the systems understanding of our students became more advanced, moving forward within each of the major CMP categories. Moreover, there was an increase in the mechanism complexity presented by the students, manifested by more students describing mechanisms at the molecular level. Thus, the 'mechanism' category and the micro level are critical components that enable students to understand system-level phenomena such as homeostasis.

Interdisciplinary education - a predator-prey model for developing a skill set in mathematics, biology and technology

NASA Astrophysics Data System (ADS)

van der Hoff, Quay

2017-08-01

The science of biology has been transforming dramatically and so the need for a stronger mathematical background for biology students has increased. Biological students reaching the senior or post-graduate level often come to realize that their mathematical background is insufficient. Similarly, students in a mathematics programme, interested in biological phenomena, find it difficult to master the complex systems encountered in biology. In short, the biologists do not have enough mathematics and the mathematicians are not being taught enough biology. The need for interdisciplinary curricula that includes disciplines such as biology, physical science, and mathematics is widely recognized, but has not been widely implemented. In this paper, it is suggested that students develop a skill set of ecology, mathematics and technology to encourage working across disciplinary boundaries. To illustrate such a skill set, a predator-prey model that contains self-limiting factors for both predator and prey is suggested. The general idea of dynamics, is introduced and students are encouraged to discover the applicability of this approach to more complex biological systems. The level of mathematics and technology required is not advanced; therefore, it is ideal for inclusion in a senior-level or introductory graduate-level course for students interested in mathematical biology.

From Noise to Order: The Psychological Development of Knowledge and Phenocopy in Biology

ERIC Educational Resources Information Center

Piaget, Jean

1975-01-01

Shows that one of the most general processes in the development of cognitive structures consists in replacing exogenous knowledge by endogenous reconstructions that reconstitute the same forms but incorporate them into systems whose internal composition is a pre-requisite. Biologically equivalent process is discussed. (Author/AM)

75 FR 62820 - Screening Framework Guidance for Providers of Synthetic Double-Stranded DNA

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-13

... I. Summary Synthetic biology, the developing interdisciplinary field that focuses on both the design and fabrication of novel biological components and systems as well as the re-design and fabrication of... develop, maintain, and document protocols to determine if a sequence ``hit'' qualifies as a true...

Natural production of biological optical systems

NASA Astrophysics Data System (ADS)

Choi, Seung Ho; Kim, Young L.

2015-03-01

Synthesis and production in nature often provide ideas to design and fabricate advanced biomimetic photonic materials and structures, leading to excellent physical properties and enhanced performance. In addition, the recognition and utilization of natural or biological substances have been typical routes to develop biocompatible and biodegradable materials for medical applications. In this respect, biological lasers utilizing such biomaterials and biostructures have been received considerable attention, given a variety of implications and potentials for bioimaging, biosensing, implantation, and therapy. However, without relying on industrial facilities, eco-friendly massive production of such optical components or systems has not yet been investigated. We show examples of bioproduction of biological lasers using agriculture and fisheries. We anticipate that such approaches will open new possibilities for scalable eco-friendly `green' production of biological photonics components and systems.

Applications of systems approaches in the study of rheumatic diseases.

PubMed

Kim, Ki-Jo; Lee, Saseong; Kim, Wan-Uk

2015-03-01

The complex interaction of molecules within a biological system constitutes a functional module. These modules are then acted upon by both internal and external factors, such as genetic and environmental stresses, which under certain conditions can manifest as complex disease phenotypes. Recent advances in high-throughput biological analyses, in combination with improved computational methods for data enrichment, functional annotation, and network visualization, have enabled a much deeper understanding of the mechanisms underlying important biological processes by identifying functional modules that are temporally and spatially perturbed in the context of disease development. Systems biology approaches such as these have produced compelling observations that would be impossible to replicate using classical methodologies, with greater insights expected as both the technology and methods improve in the coming years. Here, we examine the use of systems biology and network analysis in the study of a wide range of rheumatic diseases to better understand the underlying molecular and clinical features.

A Philosophical Perspective on Evolutionary Systems Biology

PubMed Central

Soyer, Orkun S.; Siegal, Mark L.

2015-01-01

Evolutionary systems biology (ESB) is an emerging hybrid approach that integrates methods, models, and data from evolutionary and systems biology. Drawing on themes that arose at a cross-disciplinary meeting on ESB in 2013, we discuss in detail some of the explanatory friction that arises in the interaction between evolutionary and systems biology. These tensions appear because of different modeling approaches, diverse explanatory aims and strategies, and divergent views about the scope of the evolutionary synthesis. We locate these discussions in the context of long-running philosophical deliberations on explanation, modeling, and theoretical synthesis. We show how many of the issues central to ESB’s progress can be understood as general philosophical problems. The benefits of addressing these philosophical issues feed back into philosophy too, because ESB provides excellent examples of scientific practice for the development of philosophy of science and philosophy of biology. PMID:26085823

Federal Research and Development Funding: FY2010

DTIC Science & Technology

2009-07-15

6.5 focus on the development of specific weapon systems or components (e.g., the Joint Strike Fighter or missile defense systems), for which an...separate item in FY2009. The House bill would provide $15 million more than the request for chemical and biological basic research and would provide $10...Maritime 25 33 40 40 40 Chemical and Biological 208 200 207 222 207 Command, Control, and Interoperability 57 75 80 81 83 Explosives 78 96 121

Directed Evolution as a Powerful Synthetic Biology Tool

PubMed Central

Cobb, Ryan E.; Sun, Ning; Zhao, Huimin

2012-01-01

At the heart of synthetic biology lies the goal of rationally engineering a complete biological system to achieve a specific objective, such as bioremediation and synthesis of a valuable drug, chemical, or biofuel molecule. However, the inherent complexity of natural biological systems has heretofore precluded generalized application of this approach. Directed evolution, a process which mimics Darwinian selection on a laboratory scale, has allowed significant strides to be made in the field of synthetic biology by allowing rapid identification of desired properties from large libraries of variants. Improvement in biocatalyst activity and stability, engineering of biosynthetic pathways, tuning of functional regulatory systems and logic circuits, and development of desired complex phenotypes in industrial host organisms have all been achieved by way of directed evolution. Here, we review recent contributions of directed evolution to synthetic biology at the protein, pathway, network, and whole cell levels. PMID:22465795

Social relationships and their biological correlates: Coronary Artery Risk Development in Young Adults (CARDIA) study.

PubMed

Seeman, Teresa E; Gruenewald, Tara L; Cohen, Sheldon; Williams, David R; Matthews, Karen A

2014-05-01

Analyses test the hypothesis that aspects of social relationships (quantity of ties, social support and social strain) are associated with differences in levels of biological risk across multiple major physiological regulatory systems and consequently overall multi-systems risk (i.e., allostatic load [AL]). Data are from the Coronary Artery Risk Development in Young Adults (CARDIA) study--a bi-ethnic, prospective, multi-center epidemiological study, initiated in 1985-1986 to track the development of cardiovascular risk in young adulthood (N=5115). At the year 15 follow-up when participants were between 32 and 45 years of age, additional social and biological data were collected; biological data used to assess AL were collected at the Oakland, CA and Chicago, IL sites (N=844). Social strains were most strongly and positively related to overall AL (Cohen's d=.79 for highest vs. lowest quartile), and to each of its component biological subsystems, independent of social ties and support as well as sociodemographics and health behaviors. Social ties and emotional support were also negatively related to AL (Cohen's d=.33 and d=.44 for lowest vs. highest quartiles of ties and support, respectively) though controls for social strains reduced these associations to non-significance. Social support and social strain were more strongly related to overall AL than to any of its component subscales while social ties were less strongly related to AL and to its component subscales. There was no evidence that effects differed by sex, age or ethnicity. Findings focus attention on the particularly strong relationship between social strains and profiles of biological risk and support the cumulative impact of social factors on biological risks, showing larger effects for cumulative AL than for any of the individual biological systems. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Principle directions for the creation and organization of the system of sanitary-epidemiological safety during the preparations for the XXII Olympic Winter Games and XI Paralympic Winter Games 2014 in Sochi].

PubMed

Onishchenko, G G; Bragina, I V; Ezhlova, E B; Demina, V P; Gorskiĭ, A A; Gus'kov, A S; Aksenova, O I; Ivanov, G E; Klindukhov, V P; Nikolaevich, P N; Grechanaia, T B; Kulichenko, A N; Maletskaia, O V; Manin, E A; Parkhomenko, V V; Kulichenko, O A

2015-01-01

The paper generalizes the experience of formation of protection system against biological threats and ensuring sanitary and epidemiological welfare during preparation for the XXII Olympic Winter Games and XI Paralympic Winter Games of 2014 in Sochi. The basic steps for creating this system, since 2007, participation and role of Rospotrebnadzor in this process are shown. The paper deals with such questions as the governmental and administrative structures with federal agencies interaction, development of a regulatory framework governing the safety system of the Olympic Games, development of algorithms of information exchange and management decisions, biological safety in developing infrastructure in Sochi.

A dedicated database system for handling multi-level data in systems biology.

PubMed

Pornputtapong, Natapol; Wanichthanarak, Kwanjeera; Nilsson, Avlant; Nookaew, Intawat; Nielsen, Jens

2014-01-01

Advances in high-throughput technologies have enabled extensive generation of multi-level omics data. These data are crucial for systems biology research, though they are complex, heterogeneous, highly dynamic, incomplete and distributed among public databases. This leads to difficulties in data accessibility and often results in errors when data are merged and integrated from varied resources. Therefore, integration and management of systems biological data remain very challenging. To overcome this, we designed and developed a dedicated database system that can serve and solve the vital issues in data management and hereby facilitate data integration, modeling and analysis in systems biology within a sole database. In addition, a yeast data repository was implemented as an integrated database environment which is operated by the database system. Two applications were implemented to demonstrate extensibility and utilization of the system. Both illustrate how the user can access the database via the web query function and implemented scripts. These scripts are specific for two sample cases: 1) Detecting the pheromone pathway in protein interaction networks; and 2) Finding metabolic reactions regulated by Snf1 kinase. In this study we present the design of database system which offers an extensible environment to efficiently capture the majority of biological entities and relations encountered in systems biology. Critical functions and control processes were designed and implemented to ensure consistent, efficient, secure and reliable transactions. The two sample cases on the yeast integrated data clearly demonstrate the value of a sole database environment for systems biology research.

GEM System: automatic prototyping of cell-wide metabolic pathway models from genomes.

PubMed

Arakawa, Kazuharu; Yamada, Yohei; Shinoda, Kosaku; Nakayama, Yoichi; Tomita, Masaru

2006-03-23

Successful realization of a "systems biology" approach to analyzing cells is a grand challenge for our understanding of life. However, current modeling approaches to cell simulation are labor-intensive, manual affairs, and therefore constitute a major bottleneck in the evolution of computational cell biology. We developed the Genome-based Modeling (GEM) System for the purpose of automatically prototyping simulation models of cell-wide metabolic pathways from genome sequences and other public biological information. Models generated by the GEM System include an entire Escherichia coli metabolism model comprising 968 reactions of 1195 metabolites, achieving 100% coverage when compared with the KEGG database, 92.38% with the EcoCyc database, and 95.06% with iJR904 genome-scale model. The GEM System prototypes qualitative models to reduce the labor-intensive tasks required for systems biology research. Models of over 90 bacterial genomes are available at our web site.

The painted turtle, Chrysemys picta: a model system for vertebrate evolution, ecology, and human health.

PubMed

Valenzuela, Nicole

2009-07-01

Painted turtles (Chrysemys picta) are representatives of a vertebrate clade whose biology and phylogenetic position hold a key to our understanding of fundamental aspects of vertebrate evolution. These features make them an ideal emerging model system. Extensive ecological and physiological research provide the context in which to place new research advances in evolutionary genetics, genomics, evolutionary developmental biology, and ecological developmental biology which are enabled by current resources, such as a bacterial artificial chromosome (BAC) library of C. picta, and the imminent development of additional ones such as genome sequences and cDNA and expressed sequence tag (EST) libraries. This integrative approach will allow the research community to continue making advances to provide functional and evolutionary explanations for the lability of biological traits found not only among reptiles but vertebrates in general. Moreover, because humans and reptiles share a common ancestor, and given the ease of using nonplacental vertebrates in experimental biology compared with mammalian embryos, painted turtles are also an emerging model system for biomedical research. For example, painted turtles have been studied to understand many biological responses to overwintering and anoxia, as potential sentinels for environmental xenobiotics, and as a model to decipher the ecology and evolution of sexual development and reproduction. Thus, painted turtles are an excellent reptilian model system for studies with human health, environmental, ecological, and evolutionary significance.

Island biogeography: Taking the long view of nature's laboratories.

PubMed

Whittaker, Robert J; Fernández-Palacios, José María; Matthews, Thomas J; Borregaard, Michael K; Triantis, Kostas A

2017-09-01

Islands provide classic model biological systems. We review how growing appreciation of geoenvironmental dynamics of marine islands has led to advances in island biogeographic theory accommodating both evolutionary and ecological phenomena. Recognition of distinct island geodynamics permits general models to be developed and modified to account for patterns of diversity, diversification, lineage development, and trait evolution within and across island archipelagos. Emergent patterns of diversity include predictable variation in island species-area relationships, progression rule colonization from older to younger land masses, and syndromes including loss of dispersability and secondary woodiness in herbaceous plant lineages. Further developments in Earth system science, molecular biology, and trait data for islands hold continued promise for unlocking many of the unresolved questions in evolutionary biology and biogeography. Copyright © 2017, American Association for the Advancement of Science.

Approaches to Quality Risk Management When Using Single-Use Systems in the Manufacture of Biologics.

PubMed

Ishii-Watabe, Akiko; Hirose, Akihiko; Katori, Noriko; Hashii, Norikata; Arai, Susumu; Awatsu, Hirotoshi; Eiza, Akira; Hara, Yoshiaki; Hattori, Hideshi; Inoue, Tomomi; Isono, Tetsuya; Iwakura, Masahiro; Kajihara, Daisuke; Kasahara, Nobuo; Matsuda, Hiroyuki; Murakami, Sei; Nakagawa, Taishiro; Okumura, Takehiro; Omasa, Takeshi; Takuma, Shinya; Terashima, Iyo; Tsukahara, Masayoshi; Tsutsui, Maiko; Yano, Takahiro; Kawasaki, Nana

2015-10-01

Biologics manufacturing technology has made great progress in the last decade. One of the most promising new technologies is the single-use system, which has improved the efficiency of biologics manufacturing processes. To ensure safety of biologics when employing such single-use systems in the manufacturing process, various issues need to be considered including possible extractables/leachables and particles arising from the components used in single-use systems. Japanese pharmaceutical manufacturers, together with single-use suppliers, members of the academia and regulatory authorities have discussed the risks of using single-use systems and established control strategies for the quality assurance of biologics. In this study, we describe approaches for quality risk management when employing single-use systems in the manufacturing of biologics. We consider the potential impact of impurities related to single-use components on drug safety and the potential impact of the single-use system on other critical quality attributes as well as the stable supply of biologics. We also suggest a risk-mitigating strategy combining multiple control methods which includes the selection of appropriate single-use components, their inspections upon receipt and before releasing for use and qualification of single-use systems. Communication between suppliers of single-use systems and the users, as well as change controls in the facilities both of suppliers and users, are also important in risk-mitigating strategies. Implementing these control strategies can mitigate the risks attributed to the use of single-use systems. This study will be useful in promoting the development of biologics as well as in ensuring their safety, quality and stable supply.

A methodology for global-sensitivity analysis of time-dependent outputs in systems biology modelling.

PubMed

Sumner, T; Shephard, E; Bogle, I D L

2012-09-07

One of the main challenges in the development of mathematical and computational models of biological systems is the precise estimation of parameter values. Understanding the effects of uncertainties in parameter values on model behaviour is crucial to the successful use of these models. Global sensitivity analysis (SA) can be used to quantify the variability in model predictions resulting from the uncertainty in multiple parameters and to shed light on the biological mechanisms driving system behaviour. We present a new methodology for global SA in systems biology which is computationally efficient and can be used to identify the key parameters and their interactions which drive the dynamic behaviour of a complex biological model. The approach combines functional principal component analysis with established global SA techniques. The methodology is applied to a model of the insulin signalling pathway, defects of which are a major cause of type 2 diabetes and a number of key features of the system are identified.

Engineered Living Materials: Prospects and Challenges for Using Biological Systems to Direct the Assembly of Smart Materials.

PubMed

Nguyen, Peter Q; Courchesne, Noémie-Manuelle Dorval; Duraj-Thatte, Anna; Praveschotinunt, Pichet; Joshi, Neel S

2018-05-01

Vast potential exists for the development of novel, engineered platforms that manipulate biology for the production of programmed advanced materials. Such systems would possess the autonomous, adaptive, and self-healing characteristics of living organisms, but would be engineered with the goal of assembling bulk materials with designer physicochemical or mechanical properties, across multiple length scales. Early efforts toward such engineered living materials (ELMs) are reviewed here, with an emphasis on engineered bacterial systems, living composite materials which integrate inorganic components, successful examples of large-scale implementation, and production methods. In addition, a conceptual exploration of the fundamental criteria of ELM technology and its future challenges is presented. Cradled within the rich intersection of synthetic biology and self-assembling materials, the development of ELM technologies allows the power of biology to be leveraged to grow complex structures and objects using a palette of bio-nanomaterials. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Systems biology of stored blood cells: can it help to extend the expiration date?

PubMed

Paglia, Giuseppe; Palsson, Bernhard Ø; Sigurjonsson, Olafur E

2012-12-05

With increasingly stringent regulations regarding deferral and elimination of blood donors it will become increasingly important to extend the expiration date of blood components beyond the current allowed storage periods. One reason for the storage time limit for blood components is that platelets and red blood cells develop a condition called storage lesions during their storage in plastic blood containers. Systems biology provides comprehensive bio-chemical descriptions of organisms through quantitative measurements and data integration in mathematical models. The biological knowledge for a target organism can be translated in a mathematical format and used to compute physiological properties. The use of systems biology represents a concrete solution in the study of blood cell storage lesions, and it may open up new avenues towards developing better storage methods and better storage media, thereby extending the storage period of blood components. This article is part of a Special Issue entitled: Integrated omics. Copyright © 2012 Elsevier B.V. All rights reserved.

Life Support Goals Including High Closure and Low Mass Should Be Reconsidered Using Systems Analysis

NASA Technical Reports Server (NTRS)

Jones, Harry W.

2017-01-01

Recycling space life support systems have been built and tested since the 1960s and have operated on the International Space Station (ISS) since the mid 2000s. The development of space life support has been guided by a general consensus focused on two important related goals, increasing system closure and reducing launch mass. High closure is achieved by recycling crew waste products such as carbon dioxide and condensed humidity. Recycling directly reduces the mass of oxygen and water for the crew that must be launched from Earth. The launch mass of life support can be further reduced by developing recycling systems with lower hardware mass and reduced power. The life support consensus has also favored using biological systems. The goal of increasing closure using biological systems suggests that food should be grown in space and that biological processors be used for air, water, and waste recycling. The goal of reducing launch mass led to use of Equivalent System Mass (ESM) in life support advocacy and technology selection. The recent consensus assumes that the recycling systems architecture developed in the 1960s and implemented on ISS will be used on all future long missions. NASA and other project organizations use the standard systems engineering process to guide hardware development. The systems process was used to develop ISS life support, but it has been less emphasized in planning future systems for the moon and Mars. Since such missions are far in the future, there has been less immediate need for systems engineering analysis to consider trade-offs, reliability, and Life Cycle Cost (LCC). Preliminary systems analysis suggests that the life support consensus concepts should be revised to reflect systems engineering requirements.

2016 Summer Series - Michael Flynn - Synthetic Biological Membrane

NASA Image and Video Library

2016-08-02

Full understanding leads to creation capability, which results in customization capacity. Synthetic biology uses our knowledge of biology to engineer novel biological devices or organisms that can perform tasks not found in nature. For Human space exploration, synthetic biology approaches will reduce risk, mass carried and increase Human reach. Michael Flynn will discuss the International Space Station (ISS) water recycling and his current work on developing a water filtration system capable of self-repair.

Carbon dioxide evolution rate as a method to monitor and control an aerobic biological waste treatment system

NASA Technical Reports Server (NTRS)

Lee, S. S.; Shuler, M. L.

1986-01-01

An experimental system was developed to study the microbial growth kinetic of an undefined mixed culture in an erobic biological waste treatment process. The experimental results were used to develop a mathematical model that can predict the performance of a bioreactor. The bioreactor will be used to regeneratively treat waste material which is expected to be generated during a long term manned space mission. Since the presence of insoluble particles in the chemically undefined complex media made estimating biomass very difficult in the real system, a clean system was devised to study the microbial growth from the soluble substrate.

Improved Protein Arrays for Quantitative Systems Analysis of the Dynamics of Signaling Pathway Interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Chin-Rang

Astronauts and workers in nuclear plants who repeatedly exposed to low doses of ionizing radiation (IR, <10 cGy) are likely to incur specific changes in signal transduction and gene expression in various tissues of their body. Remarkable advances in high throughput genomics and proteomics technologies enable researchers to broaden their focus from examining single gene/protein kinetics to better understanding global gene/protein expression profiling and biological pathway analyses, namely Systems Biology. An ultimate goal of systems biology is to develop dynamic mathematical models of interacting biological systems capable of simulating living systems in a computer. This Glue Grant is to complementmore » Dr. Boothman’s existing DOE grant (No. DE-FG02-06ER64186) entitled “The IGF1/IGF-1R-MAPK-Secretory Clusterin (sCLU) Pathway: Mediator of a Low Dose IR-Inducible Bystander Effect” to develop sensitive and quantitative proteomic technology that suitable for low dose radiobiology researches. An improved version of quantitative protein array platform utilizing linear Quantum dot signaling for systematically measuring protein levels and phosphorylation states for systems biology modeling is presented. The signals are amplified by a confocal laser Quantum dot scanner resulting in ~1000-fold more sensitivity than traditional Western blots and show the good linearity that is impossible for the signals of HRP-amplification. Therefore this improved protein array technology is suitable to detect weak responses of low dose radiation. Software is developed to facilitate the quantitative readout of signaling network activities. Kinetics of EGFRvIII mutant signaling was analyzed to quantify cross-talks between EGFR and other signaling pathways.« less

The challenges of informatics in synthetic biology: from biomolecular networks to artificial organisms

PubMed Central

Ramoni, Marco F.

2010-01-01

The field of synthetic biology holds an inspiring vision for the future; it integrates computational analysis, biological data and the systems engineering paradigm in the design of new biological machines and systems. These biological machines are built from basic biomolecular components analogous to electrical devices, and the information flow among these components requires the augmentation of biological insight with the power of a formal approach to information management. Here we review the informatics challenges in synthetic biology along three dimensions: in silico, in vitro and in vivo. First, we describe state of the art of the in silico support of synthetic biology, from the specific data exchange formats, to the most popular software platforms and algorithms. Next, we cast in vitro synthetic biology in terms of information flow, and discuss genetic fidelity in DNA manipulation, development strategies of biological parts and the regulation of biomolecular networks. Finally, we explore how the engineering chassis can manipulate biological circuitries in vivo to give rise to future artificial organisms. PMID:19906839

New tools for the analysis of glial cell biology in Drosophila.

PubMed

Awasaki, Takeshi; Lee, Tzumin

2011-09-01

Because of its genetic, molecular, and behavioral tractability, Drosophila has emerged as a powerful model system for studying molecular and cellular mechanisms underlying the development and function of nervous systems. The Drosophila nervous system has fewer neurons and exhibits a lower glia:neuron ratio than is seen in vertebrate nervous systems. Despite the simplicity of the Drosophila nervous system, glial organization in flies is as sophisticated as it is in vertebrates. Furthermore, fly glial cells play vital roles in neural development and behavior. In addition, powerful genetic tools are continuously being created to explore cell function in vivo. In taking advantage of these features, the fly nervous system serves as an excellent model system to study general aspects of glial cell development and function in vivo. In this article, we review and discuss advanced genetic tools that are potentially useful for understanding glial cell biology in Drosophila. Copyright © 2011 Wiley-Liss, Inc.

Improving the explanation capabilities of advisory systems

NASA Technical Reports Server (NTRS)

Porter, Bruce; Souther, Art

1993-01-01

A major limitation of current advisory systems (e.g., intelligent tutoring systems and expert systems) is their restricted ability to give explanations. The goal of our research is to develop and evaluate a flexible explanation facility, one that can dynamically generate responses to questions not anticipated by the system's designers and that can tailor these responses to individual users. To achieve this flexibility, we are developing a large knowledge base, a viewpoint construction facility, and a modeling facility. In the long term we plan to build and evaluate advisory systems with flexible explanation facilities for scientists in numerous domains. In the short term, we are focusing on a single complex domain in biological science, and we are working toward two important milestones: (1) building and evaluating an advisory system with a flexible explanation facility for freshman-level students studying biology; and (2) developing general methods and tools for building similar explanation facilities in other domains.

Improving the explanation capabilities of advisory systems

NASA Technical Reports Server (NTRS)

Porter, Bruce; Souther, Art

1994-01-01

A major limitation of current advisory systems (e.g., intelligent tutoring systems and expert systems) is their restricted ability to give explanations. The goal of our research is to develop and evaluate a flexible explanation facility, one that can dynamically generate responses to questions not anticipated by the system's designers and that can tailor these responses to individual users. To achieve this flexibility, we are developing a large knowledge base, a viewpoint construction facility, and a modeling facility. In the long term we plan to build and evaluate advisory systems with flexible explanation facilities for scientists in numerous domains. In the short term, we are focusing on a single complex domain in biological science, and we are working toward two important milestones: (1) building and evaluating an advisory system with a flexible explanation facility for freshman-level students studying biology, and (2) developing general methods and tools for building similar explanation facilities in other domains.

Protein design in systems metabolic engineering for industrial strain development.

PubMed

Chen, Zhen; Zeng, An-Ping

2013-05-01

Accelerating the process of industrial bacterial host strain development, aimed at increasing productivity, generating new bio-products or utilizing alternative feedstocks, requires the integration of complementary approaches to manipulate cellular metabolism and regulatory networks. Systems metabolic engineering extends the concept of classical metabolic engineering to the systems level by incorporating the techniques used in systems biology and synthetic biology, and offers a framework for the development of the next generation of industrial strains. As one of the most useful tools of systems metabolic engineering, protein design allows us to design and optimize cellular metabolism at a molecular level. Here, we review the current strategies of protein design for engineering cellular synthetic pathways, metabolic control systems and signaling pathways, and highlight the challenges of this subfield within the context of systems metabolic engineering. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemistry meets biology in colitis-associated carcinogenesis

PubMed Central

Mangerich, Aswin; Dedon, Peter C.; Fox, James G.; Tannenbaum, Steven R.; Wogan, Gerald N.

2015-01-01

The intestine comprises an exceptional venue for a dynamic and complex interplay of numerous chemical and biological processes. Here, multiple chemical and biological systems, including the intestinal tissue itself, its associated immune system, the gut microbiota, xenobiotics, and metabolites meet and interact to form a sophisticated and tightly regulated state of tissue homoeostasis. Disturbance of this homeostasis can cause inflammatory bowel disease (IBD) – a chronic disease of multifactorial etiology that is strongly associated with increased risk for cancer development. This review addresses recent developments in research into chemical and biological mechanisms underlying the etiology of inflammation-induced colon cancer. Beginning with a general overview of reactive chemical species generated during colonic inflammation, the mechanistic interplay between chemical and biological mediators of inflammation, the role of genetic toxicology and microbial pathogenesis in disease development are discussed. When possible, we systematically compare evidence from studies utilizing human IBD patients with experimental investigations in mice. The comparison reveals that many strong pathological and mechanistic correlates exist between mouse models of colitis-associated cancer, and the clinically relevant situation in humans. We also summarize several emerging issues in the field, such as the carcinogenic potential of novel inflammation-related DNA adducts and genotoxic microbial factors, the systemic dimension of inflammation-induced genotoxicity, and the complex role of genome maintenance mechanisms during these processes. Taken together, current evidence points to the induction of genetic and epigenetic alterations by chemical and biological inflammatory stimuli ultimately leading to cancer formation. PMID:23926919

Engineering emergent multicellular behavior through synthetic adhesion

NASA Astrophysics Data System (ADS)

Glass, David; Riedel-Kruse, Ingmar

In over a decade, synthetic biology has developed increasingly robust gene networks within single cells, but constructed very few systems that demonstrate multicellular spatio-temporal dynamics. We are filling this gap in synthetic biology's toolbox by developing an E. coli self-assembly platform based on modular cell-cell adhesion. We developed a system in which adhesive selectivity is provided by a library of outer membrane-displayed peptides with intra-library specificities, while affinity is provided by consistent expression across the entire library. We further provide a biophysical model to help understand the parameter regimes in which this tool can be used to self-assemble into cellular clusters, filaments, or meshes. The combined platform will enable future development of synthetic multicellular systems for use in consortia-based metabolic engineering, in living materials, and in controlled study of minimal multicellular systems. Stanford Bio-X Bowes Fellowship.

Meeting report from the first meetings of the Computational Modeling in Biology Network (COMBINE)

PubMed Central

Le Novère, Nicolas; Hucka, Michael; Anwar, Nadia; Bader, Gary D; Demir, Emek; Moodie, Stuart; Sorokin, Anatoly

2011-01-01

The Computational Modeling in Biology Network (COMBINE), is an initiative to coordinate the development of the various community standards and formats in computational systems biology and related fields. This report summarizes the activities pursued at the first annual COMBINE meeting held in Edinburgh on October 6-9 2010 and the first HARMONY hackathon, held in New York on April 18-22 2011. The first of those meetings hosted 81 attendees. Discussions covered both official COMBINE standards-(BioPAX, SBGN and SBML), as well as emerging efforts and interoperability between different formats. The second meeting, oriented towards software developers, welcomed 59 participants and witnessed many technical discussions, development of improved standards support in community software systems and conversion between the standards. Both meetings were resounding successes and showed that the field is now mature enough to develop representation formats and related standards in a coordinated manner. PMID:22180826

Meeting report from the first meetings of the Computational Modeling in Biology Network (COMBINE).

PubMed

Le Novère, Nicolas; Hucka, Michael; Anwar, Nadia; Bader, Gary D; Demir, Emek; Moodie, Stuart; Sorokin, Anatoly

2011-11-30

The Computational Modeling in Biology Network (COMBINE), is an initiative to coordinate the development of the various community standards and formats in computational systems biology and related fields. This report summarizes the activities pursued at the first annual COMBINE meeting held in Edinburgh on October 6-9 2010 and the first HARMONY hackathon, held in New York on April 18-22 2011. The first of those meetings hosted 81 attendees. Discussions covered both official COMBINE standards-(BioPAX, SBGN and SBML), as well as emerging efforts and interoperability between different formats. The second meeting, oriented towards software developers, welcomed 59 participants and witnessed many technical discussions, development of improved standards support in community software systems and conversion between the standards. Both meetings were resounding successes and showed that the field is now mature enough to develop representation formats and related standards in a coordinated manner.

Biosensor Recognition Elements

DTIC Science & Technology

2008-01-01

Systematics, bioinformatics, systems biology, regulation, genetics, genomics, metabolism, ecology, development . Epstein - Barr Virus Latency and...and C, Simian immunodeficiency, Ebola, Rabies, Epstein – Barr , and Measles viruses as well as biological agents such as botulinum neurotoxin A/B...time metabolic vigilance via sensor based ligand specific biorecognition elements is immense. Virus -based nanoparticles have been developed for

Expanding biological data standards development processes for US IOOS: visual line transect observing community for mammal, bird, and turtle data

USGS Publications Warehouse

Fornwall, M.; Gisiner, R.; Simmons, S. E.; Moustahfid, Hassan; Canonico, G.; Halpin, P.; Goldstein, P.; Fitch, R.; Weise, M.; Cyr, N.; Palka, D.; Price, J.; Collins, D.

2012-01-01

The US Integrated Ocean Observing System (IOOS) has recently adopted standards for biological core variables in collaboration with the US Geological Survey/Ocean Biogeographic Information System (USGS/OBIS-USA) and other federal and non-federal partners. In this Community White Paper (CWP) we provide a process to bring into IOOS a rich new source of biological observing data, visual line transect surveys, and to establish quality data standards for visual line transect observations, an important source of at-sea bird, turtle and marine mammal observation data. The processes developed through this exercise will be useful for other similar biogeographic observing efforts, such as passive acoustic point and line transect observations, tagged animal data, and mark-recapture (photo-identification) methods. Furthermore, we suggest that the processes developed through this exercise will serve as a catalyst for broadening involvement by the larger marine biological data community within the goals and processes of IOOS.

The SBOL Stack: A Platform for Storing, Publishing, and Sharing Synthetic Biology Designs.

PubMed

Madsen, Curtis; McLaughlin, James Alastair; Mısırlı, Göksel; Pocock, Matthew; Flanagan, Keith; Hallinan, Jennifer; Wipat, Anil

2016-06-17

Recently, synthetic biologists have developed the Synthetic Biology Open Language (SBOL), a data exchange standard for descriptions of genetic parts, devices, modules, and systems. The goals of this standard are to allow scientists to exchange designs of biological parts and systems, to facilitate the storage of genetic designs in repositories, and to facilitate the description of genetic designs in publications. In order to achieve these goals, the development of an infrastructure to store, retrieve, and exchange SBOL data is necessary. To address this problem, we have developed the SBOL Stack, a Resource Description Framework (RDF) database specifically designed for the storage, integration, and publication of SBOL data. This database allows users to define a library of synthetic parts and designs as a service, to share SBOL data with collaborators, and to store designs of biological systems locally. The database also allows external data sources to be integrated by mapping them to the SBOL data model. The SBOL Stack includes two Web interfaces: the SBOL Stack API and SynBioHub. While the former is designed for developers, the latter allows users to upload new SBOL biological designs, download SBOL documents, search by keyword, and visualize SBOL data. Since the SBOL Stack is based on semantic Web technology, the inherent distributed querying functionality of RDF databases can be used to allow different SBOL stack databases to be queried simultaneously, and therefore, data can be shared between different institutes, centers, or other users.

The Virtual Liver Network: systems understanding from bench to bedside.

PubMed

Henney, Adriano; Coaker, Hannah

2014-01-01

Adriano Henney speaks to Hannah Coaker, Commissioning Editor. After achieving a PhD in medicine and spending many years in academic research in the field of cardiovascular disease, Adriano Henney was recruited by Zeneca Pharmaceuticals from a British Heart Foundation Senior Fellowship, where he led the exploration of new therapeutic approaches in atherosclerosis, specifically focusing on his research interests in vascular biology. Following the merger with Astra to form AstraZeneca, Henney became responsible for exploring strategic improvements to the company's approaches to pharmaceutical target identification and the reduction of attrition in early development, directing projects across research sites and across functional project teams in the USA, Sweden and the UK. This resulted in the creation of a new multidisciplinary department that focused on pathway mapping, modeling and simulation and supporting projects across research and development, which evolved into the establishment of the practice of systems biology within the company. Here, projects prototyped the application of mechanistic disease-modeling approaches in order to support the discovery of innovative new medicines, such as Iressa®. Since leaving AstraZeneca, Henney has continued his interest in systems biology, synthetic biology and systems medicine through his company, Obsidian Biomedical Consulting Ltd. He now directs a major €50 million German national flagship program – the Virtual Liver Network – which is currently the largest systems biology program in Europe.

Technology base for microgravity horticulture

NASA Technical Reports Server (NTRS)

Sauer, R. L.; Magnuson, J. W.; Scruby, R. R.; Scheld, H. W.

1987-01-01

Advanced microgravity plant biology research and life support system development for the spacecraft environment are critically hampered by the lack of a technology base. This inadequacy stems primarily from the fact that microgravity results in a lack of convective currents and phase separation as compared to the one gravity environment. A program plan is being initiated to develop this technology base. This program will provide an iterative flight development effort that will be closely integrated with both basic science investigations and advanced life support system development efforts incorporating biological processes. The critical considerations include optimum illumination methods, root aeration, root and shoot support, and heat rejection and gas exchange in the plant canopy.

Integrative systems and synthetic biology of cell-matrix adhesion sites.

PubMed

Zamir, Eli

2016-09-02

The complexity of cell-matrix adhesion convolves its roles in the development and functioning of multicellular organisms and their evolutionary tinkering. Cell-matrix adhesion is mediated by sites along the plasma membrane that anchor the actin cytoskeleton to the matrix via a large number of proteins, collectively called the integrin adhesome. Fundamental challenges for understanding how cell-matrix adhesion sites assemble and function arise from their multi-functionality, rapid dynamics, large number of components and molecular diversity. Systems biology faces these challenges in its strive to understand how the integrin adhesome gives rise to functional adhesion sites. Synthetic biology enables engineering intracellular modules and circuits with properties of interest. In this review I discuss some of the fundamental questions in systems biology of cell-matrix adhesion and how synthetic biology can help addressing them.

Peptide π-Electron Conjugates: Organic Electronics for Biology?

PubMed

Ardoña, Herdeline Ann M; Tovar, John D

2015-12-16

Highly ordered arrays of π-conjugated molecules are often viewed as a prerequisite for effective charge-transporting materials. Studies involving these materials have traditionally focused on organic electronic devices, with more recent emphasis on biological systems. In order to facilitate the transition to biological environments, biomolecules that can promote hierarchical ordering and water solubility are often covalently appended to the π-electron unit. This review highlights recent work on π-conjugated systems bound to peptide moieties that exhibit self-assembly and aims to provide an overview on the development and emerging applications of peptide-based supramolecular π-electron systems.

From noise to synthetic nucleoli: can synthetic biology achieve new insights?

PubMed

Ciechonska, Marta; Grob, Alice; Isalan, Mark

2016-04-18

Synthetic biology aims to re-organise and control biological components to make functional devices. Along the way, the iterative process of designing and testing gene circuits has the potential to yield many insights into the functioning of the underlying chassis of cells. Thus, synthetic biology is converging with disciplines such as systems biology and even classical cell biology, to give a new level of predictability to gene expression, cell metabolism and cellular signalling networks. This review gives an overview of the contributions that synthetic biology has made in understanding gene expression, in terms of cell heterogeneity (noise), the coupling of growth and energy usage to expression, and spatiotemporal considerations. We mainly compare progress in bacterial and mammalian systems, which have some of the most-developed engineering frameworks. Overall, one view of synthetic biology can be neatly summarised as "creating in order to understand."

Invited Review Article: Current State of Research on Biological Effects of Terahertz Radiation

NASA Astrophysics Data System (ADS)

Wilmink, Gerald J.; Grundt, Jessica E.

2011-10-01

Terahertz (THz) imaging and sensing technologies are increasingly being used in a host of medical, military, and security applications. For example, THz systems are now being tested at international airports for security screening purposes, at major medical centers for cancer and burn diagnosis, and at border patrol checkpoints for identification of concealed explosives, drugs, and weapons. Recent advances in THz applications have stimulated renewed interest regarding the biological effects associated with this frequency range. Biological effects studies are a valuable type of basic science research because they serve to enhance our fundamental understanding of the mechanisms that govern THz interactions with biological systems. Such studies are also important because they often times lay the foundation for the development of future applications. In addition, from a practical standpoint, THz biological effects research is also necessary for accurate health hazard evaluation, the development of empirically-based safety standards, and for the safe use of THz systems. Given the importance and timeliness of THz bioeffects data, the purpose of this review is twofold. First, to provide readers with a common reference, which contains the necessary background concepts in biophysics and THz technology, that are required to both conduct and evaluate THz biological research. Second, to provide a critical review of the scientific literature.

Model reduction of multiscale chemical langevin equations: a numerical case study.

PubMed

Sotiropoulos, Vassilios; Contou-Carrere, Marie-Nathalie; Daoutidis, Prodromos; Kaznessis, Yiannis N

2009-01-01

Two very important characteristics of biological reaction networks need to be considered carefully when modeling these systems. First, models must account for the inherent probabilistic nature of systems far from the thermodynamic limit. Often, biological systems cannot be modeled with traditional continuous-deterministic models. Second, models must take into consideration the disparate spectrum of time scales observed in biological phenomena, such as slow transcription events and fast dimerization reactions. In the last decade, significant efforts have been expended on the development of stochastic chemical kinetics models to capture the dynamics of biomolecular systems, and on the development of robust multiscale algorithms, able to handle stiffness. In this paper, the focus is on the dynamics of reaction sets governed by stiff chemical Langevin equations, i.e., stiff stochastic differential equations. These are particularly challenging systems to model, requiring prohibitively small integration step sizes. We describe and illustrate the application of a semianalytical reduction framework for chemical Langevin equations that results in significant gains in computational cost.

Adhesion control by inflation: implications from biology to artificial attachment device

NASA Astrophysics Data System (ADS)

Dening, Kirstin; Heepe, Lars; Afferrante, Luciano; Carbone, Giuseppe; Gorb, Stanislav N.

2014-08-01

There is an increasing demand for materials that incorporate advanced adhesion properties, such as an ability to adhere in a reversible and controllable manner. In biological systems, these features are known from adhesive pads of the tree frog, Litoria caerulea, and the bush-cricket, Tettigonia viridissima. These species have convergently developed soft, hemispherically shaped pads that might be able to control their adhesion through active changing the curvature of the pad. Inspired by these biological systems, an artificial model system is developed here. It consists of an inflatable membrane clamped to the metallic cylinder and filled with air. Pull-off force measurements of the membrane surface were conducted in contact with the membrane at five different radii of curvature r c with (1) a smooth polyvinylsiloxane membrane and (2) mushroom-shaped adhesive microstructured membrane made of the same polymer. The hypothesis that an increased internal pressure, acting on the membrane, reduces the radius of the membrane curvature, resulting in turn in a lower pull-off force, is verified. Such an active control of adhesion, inspired by biological models, will lead to the development of industrial pick-and-drop devices with controllable adhesive properties.

Developing and Evaluating an Eighth Grade Curriculum Unit That Links Foundational Chemistry to Biological Growth: Designing Professional Development to Support Teaching

ERIC Educational Resources Information Center

Kruse, Rebecca; Howes, Elaine V.; Carlson, Janet; Roth, Kathleen; Bourdelat-Parks, Brooke

2013-01-01

AAAS and BSCS are collaborating to develop and study a curriculum unit that supports students' ability to explain a variety of biological processes such as growth in chemical terms. The unit provides conceptual coherence between chemical processes in nonliving and living systems through the core idea of atom rearrangement and conservation during…

Automatic Compilation from High-Level Biologically-Oriented Programming Language to Genetic Regulatory Networks

PubMed Central

Beal, Jacob; Lu, Ting; Weiss, Ron

2011-01-01

Background The field of synthetic biology promises to revolutionize our ability to engineer biological systems, providing important benefits for a variety of applications. Recent advances in DNA synthesis and automated DNA assembly technologies suggest that it is now possible to construct synthetic systems of significant complexity. However, while a variety of novel genetic devices and small engineered gene networks have been successfully demonstrated, the regulatory complexity of synthetic systems that have been reported recently has somewhat plateaued due to a variety of factors, including the complexity of biology itself and the lag in our ability to design and optimize sophisticated biological circuitry. Methodology/Principal Findings To address the gap between DNA synthesis and circuit design capabilities, we present a platform that enables synthetic biologists to express desired behavior using a convenient high-level biologically-oriented programming language, Proto. The high level specification is compiled, using a regulatory motif based mechanism, to a gene network, optimized, and then converted to a computational simulation for numerical verification. Through several example programs we illustrate the automated process of biological system design with our platform, and show that our compiler optimizations can yield significant reductions in the number of genes () and latency of the optimized engineered gene networks. Conclusions/Significance Our platform provides a convenient and accessible tool for the automated design of sophisticated synthetic biological systems, bridging an important gap between DNA synthesis and circuit design capabilities. Our platform is user-friendly and features biologically relevant compiler optimizations, providing an important foundation for the development of sophisticated biological systems. PMID:21850228

Automatic compilation from high-level biologically-oriented programming language to genetic regulatory networks.

PubMed

Beal, Jacob; Lu, Ting; Weiss, Ron

2011-01-01

The field of synthetic biology promises to revolutionize our ability to engineer biological systems, providing important benefits for a variety of applications. Recent advances in DNA synthesis and automated DNA assembly technologies suggest that it is now possible to construct synthetic systems of significant complexity. However, while a variety of novel genetic devices and small engineered gene networks have been successfully demonstrated, the regulatory complexity of synthetic systems that have been reported recently has somewhat plateaued due to a variety of factors, including the complexity of biology itself and the lag in our ability to design and optimize sophisticated biological circuitry. To address the gap between DNA synthesis and circuit design capabilities, we present a platform that enables synthetic biologists to express desired behavior using a convenient high-level biologically-oriented programming language, Proto. The high level specification is compiled, using a regulatory motif based mechanism, to a gene network, optimized, and then converted to a computational simulation for numerical verification. Through several example programs we illustrate the automated process of biological system design with our platform, and show that our compiler optimizations can yield significant reductions in the number of genes (~ 50%) and latency of the optimized engineered gene networks. Our platform provides a convenient and accessible tool for the automated design of sophisticated synthetic biological systems, bridging an important gap between DNA synthesis and circuit design capabilities. Our platform is user-friendly and features biologically relevant compiler optimizations, providing an important foundation for the development of sophisticated biological systems.

A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking

PubMed Central

Gilbert, David

2016-01-01

Insights gained from multilevel computational models of biological systems can be translated into real-life applications only if the model correctness has been verified first. One of the most frequently employed in silico techniques for computational model verification is model checking. Traditional model checking approaches only consider the evolution of numeric values, such as concentrations, over time and are appropriate for computational models of small scale systems (e.g. intracellular networks). However for gaining a systems level understanding of how biological organisms function it is essential to consider more complex large scale biological systems (e.g. organs). Verifying computational models of such systems requires capturing both how numeric values and properties of (emergent) spatial structures (e.g. area of multicellular population) change over time and across multiple levels of organization, which are not considered by existing model checking approaches. To address this limitation we have developed a novel approximate probabilistic multiscale spatio-temporal meta model checking methodology for verifying multilevel computational models relative to specifications describing the desired/expected system behaviour. The methodology is generic and supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to generate it. In addition, the methodology can be automatically adapted to case study specific types of spatial structures and properties using the spatio-temporal meta model checking concept. To automate the computational model verification process we have implemented the model checking approach in the software tool Mule (http://mule.modelchecking.org). Its applicability is illustrated against four systems biology computational models previously published in the literature encoding the rat cardiovascular system dynamics, the uterine contractions of labour, the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. Our methodology and software will enable computational biologists to efficiently develop reliable multilevel computational models of biological systems. PMID:27187178

A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking.

PubMed

Pârvu, Ovidiu; Gilbert, David

2016-01-01

Insights gained from multilevel computational models of biological systems can be translated into real-life applications only if the model correctness has been verified first. One of the most frequently employed in silico techniques for computational model verification is model checking. Traditional model checking approaches only consider the evolution of numeric values, such as concentrations, over time and are appropriate for computational models of small scale systems (e.g. intracellular networks). However for gaining a systems level understanding of how biological organisms function it is essential to consider more complex large scale biological systems (e.g. organs). Verifying computational models of such systems requires capturing both how numeric values and properties of (emergent) spatial structures (e.g. area of multicellular population) change over time and across multiple levels of organization, which are not considered by existing model checking approaches. To address this limitation we have developed a novel approximate probabilistic multiscale spatio-temporal meta model checking methodology for verifying multilevel computational models relative to specifications describing the desired/expected system behaviour. The methodology is generic and supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to generate it. In addition, the methodology can be automatically adapted to case study specific types of spatial structures and properties using the spatio-temporal meta model checking concept. To automate the computational model verification process we have implemented the model checking approach in the software tool Mule (http://mule.modelchecking.org). Its applicability is illustrated against four systems biology computational models previously published in the literature encoding the rat cardiovascular system dynamics, the uterine contractions of labour, the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. Our methodology and software will enable computational biologists to efficiently develop reliable multilevel computational models of biological systems.

Just Working with the Cellular Machine: A High School Game for Teaching Molecular Biology

ERIC Educational Resources Information Center

Cardoso, Fernanda Serpa; Dumpel, Renata; Gomes da Silva, Luisa B.; Rodrigues, Carlos R.; Santos, Dilvani O.; Cabral, Lucio Mendes; Castro, Helena C.

2008-01-01

Molecular biology is a difficult comprehension subject due to its high complexity, thus requiring new teaching approaches. Herein, we developed an interdisciplinary board game involving the human immune system response against a bacterial infection for teaching molecular biology at high school. Initially, we created a database with several…

Computer-Based Semantic Network in Molecular Biology: A Demonstration.

ERIC Educational Resources Information Center

Callman, Joshua L.; And Others

This paper analyzes the hardware and software features that would be desirable in a computer-based semantic network system for representing biology knowledge. It then describes in detail a prototype network of molecular biology knowledge that has been developed using Filevision software and a Macintosh computer. The prototype contains about 100…

Synthetic Biology: Applications in the Food Sector.

PubMed

Tyagi, Ashish; Kumar, Ashwani; Aparna, S V; Mallappa, Rashmi H; Grover, Sunita; Batish, Virender Kumar

2016-08-17

Synthetic biology also termed as "genomic alchemy" represents a powerful area of science that is based on the convergence of biological sciences with systems engineering. It has been fittingly described as "moving from reading the genetic code to writing it" as it focuses on building, modeling, designing and fabricating novel biological systems using customized gene components that result in artificially created genetic circuitry. The scientifically compelling idea of the technological manipulation of life has been advocated since long time. Realization of this idea has gained momentum with development of high speed automation and the falling cost of gene sequencing and synthesis following the completion of the human genome project. Synthetic biology will certainly be instrumental in shaping the development of varying areas ranging from biomedicine, biopharmaceuticals, chemical production, food and dairy quality monitoring, packaging, and storage of food and dairy products, bioremediation and bioenergy production, etc. However, potential dangers of using synthetic life forms have to be acknowledged and adoption of policies by the scientific community to ensure safe practice while making important advancements in the ever expanding field of synthetic biology is to be fully supported and implemented.

Full Monte Carlo-Based Biologic Treatment Plan Optimization System for Intensity Modulated Carbon Ion Therapy on Graphics Processing Unit.

PubMed

Qin, Nan; Shen, Chenyang; Tsai, Min-Yu; Pinto, Marco; Tian, Zhen; Dedes, Georgios; Pompos, Arnold; Jiang, Steve B; Parodi, Katia; Jia, Xun

2018-01-01

One of the major benefits of carbon ion therapy is enhanced biological effectiveness at the Bragg peak region. For intensity modulated carbon ion therapy (IMCT), it is desirable to use Monte Carlo (MC) methods to compute the properties of each pencil beam spot for treatment planning, because of their accuracy in modeling physics processes and estimating biological effects. We previously developed goCMC, a graphics processing unit (GPU)-oriented MC engine for carbon ion therapy. The purpose of the present study was to build a biological treatment plan optimization system using goCMC. The repair-misrepair-fixation model was implemented to compute the spatial distribution of linear-quadratic model parameters for each spot. A treatment plan optimization module was developed to minimize the difference between the prescribed and actual biological effect. We used a gradient-based algorithm to solve the optimization problem. The system was embedded in the Varian Eclipse treatment planning system under a client-server architecture to achieve a user-friendly planning environment. We tested the system with a 1-dimensional homogeneous water case and 3 3-dimensional patient cases. Our system generated treatment plans with biological spread-out Bragg peaks covering the targeted regions and sparing critical structures. Using 4 NVidia GTX 1080 GPUs, the total computation time, including spot simulation, optimization, and final dose calculation, was 0.6 hour for the prostate case (8282 spots), 0.2 hour for the pancreas case (3795 spots), and 0.3 hour for the brain case (6724 spots). The computation time was dominated by MC spot simulation. We built a biological treatment plan optimization system for IMCT that performs simulations using a fast MC engine, goCMC. To the best of our knowledge, this is the first time that full MC-based IMCT inverse planning has been achieved in a clinically viable time frame. Copyright © 2017 Elsevier Inc. All rights reserved.

Concept Recognition in an Automatic Text-Processing System for the Life Sciences.

ERIC Educational Resources Information Center

Vleduts-Stokolov, Natasha

1987-01-01

Describes a system developed for the automatic recognition of biological concepts in titles of scientific articles; reports results of several pilot experiments which tested the system's performance; analyzes typical ambiguity problems encountered by the system; describes a disambiguation technique that was developed; and discusses future plans…

Joint Service Chemical and Biological Defense Program. FY00-02 Overview

DTIC Science & Technology

2001-09-01

Development. Contractors: 12 BI DS Biological Integrated Detection System (BIDS) Lead Service Bio Road HERCULES, CA Bruker Analytical Systems BILLERICA, MA...Dynamics Land Systems Division DETROIT, MI Henschel Wehrtechnik GERMANY Bruker -Franzen GERMANY Block II – TBD Milestones Block I MS III (2QFY94) Block...ground. Accessories include hoses and hose reels, two trigger-controlled spray wands , and two electrical-powered scrub brush assemblies. The M22

Toward an integrated software platform for systems pharmacology

PubMed Central

Ghosh, Samik; Matsuoka, Yukiko; Asai, Yoshiyuki; Hsin, Kun-Yi; Kitano, Hiroaki

2013-01-01

Understanding complex biological systems requires the extensive support of computational tools. This is particularly true for systems pharmacology, which aims to understand the action of drugs and their interactions in a systems context. Computational models play an important role as they can be viewed as an explicit representation of biological hypotheses to be tested. A series of software and data resources are used for model development, verification and exploration of the possible behaviors of biological systems using the model that may not be possible or not cost effective by experiments. Software platforms play a dominant role in creativity and productivity support and have transformed many industries, techniques that can be applied to biology as well. Establishing an integrated software platform will be the next important step in the field. © 2013 The Authors. Biopharmaceutics & Drug Disposition published by John Wiley & Sons, Ltd. PMID:24150748

Design and control strategies for CELSS - Integrating mechanistic paradigms and biological complexities

NASA Technical Reports Server (NTRS)

Moore, B., III; Kaufmann, R.; Reinhold, C.

1981-01-01

Systems analysis and control theory consideration are given to simulations of both individual components and total systems, in order to develop a reliable control strategy for a Controlled Ecological Life Support System (CELSS) which includes complex biological components. Because of the numerous nonlinearities and tight coupling within the biological component, classical control theory may be inadequate and the statistical analysis of factorial experiments more useful. The range in control characteristics of particular species may simplify the overall task by providing an appropriate balance of stability and controllability to match species function in the overall design. The ultimate goal of this research is the coordination of biological and mechanical subsystems in order to achieve a self-supporting environment.

Systems biology of seeds: deciphering the molecular mechanisms of seed storage, dormancy and onset of germination.

PubMed

Sreenivasulu, Nese

2017-05-01

Seeds are heterogeneous storage reserves with wide array of storage compounds that include various soluble carbohydrates, starch polymer, storage proteins and lipids. These stored reserves comprise 70% of the world's caloric intake in the form of food and animal feed produced through sustainable agriculture, which contributes to food and nutritional security. Seed systems biology remains an enigmatic subject in understanding seed storage processes, maturation and pre-germinative metabolism. The reviews and research articles covered in this special issue of Plant Cell Reports highlight recent advances made in the area of seed biology that cover various systems biology applications such as gene regulatory networks, metabolomics, epigenetics and the role of micro-RNA in seed development.

Developing optimal input design strategies in cancer systems biology with applications to microfluidic device engineering.

PubMed

Menolascina, Filippo; Bellomo, Domenico; Maiwald, Thomas; Bevilacqua, Vitoantonio; Ciminelli, Caterina; Paradiso, Angelo; Tommasi, Stefania

2009-10-15

Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the intrinsic characteristics of complex pathologies like cancer: acquiring information for a system understanding of complex reaction networks is time consuming and expensive. Stimulus response experiments (SRE) have been used to gain a deeper insight into the details of biochemical mechanisms underlying cell life and functioning. Optimisation of the input time-profile, however, still remains a major area of research due to the complexity of the problem and its relevance for the task of information retrieval in systems biology-related experiments. We have addressed the problem of quantifying the information associated to an experiment using the Fisher Information Matrix and we have proposed an optimal experimental design strategy based on evolutionary algorithm to cope with the problem of information gathering in Systems Biology. On the basis of the theoretical results obtained in the field of control systems theory, we have studied the dynamical properties of the signals to be used in cell stimulation. The results of this study have been used to develop a microfluidic device for the automation of the process of cell stimulation for system identification. We have applied the proposed approach to the Epidermal Growth Factor Receptor pathway and we observed that it minimises the amount of parametric uncertainty associated to the identified model. A statistical framework based on Monte-Carlo estimations of the uncertainty ellipsoid confirmed the superiority of optimally designed experiments over canonical inputs. The proposed approach can be easily extended to multiobjective formulations that can also take advantage of identifiability analysis. Moreover, the availability of fully automated microfluidic platforms explicitly developed for the task of biochemical model identification will hopefully reduce the effects of the 'data rich--data poor' paradox in Systems Biology.

Advances and applications of occupancy models

USGS Publications Warehouse

Bailey, Larissa; MacKenzie, Darry I.; Nichols, James D.

2013-01-01

Summary: The past decade has seen an explosion in the development and application of models aimed at estimating species occurrence and occupancy dynamics while accounting for possible non-detection or species misidentification. We discuss some recent occupancy estimation methods and the biological systems that motivated their development. Collectively, these models offer tremendous flexibility, but simultaneously place added demands on the investigator. Unlike many mark–recapture scenarios, investigators utilizing occupancy models have the ability, and responsibility, to define their sample units (i.e. sites), replicate sampling occasions, time period over which species occurrence is assumed to be static and even the criteria that constitute ‘detection’ of a target species. Subsequent biological inference and interpretation of model parameters depend on these definitions and the ability to meet model assumptions. We demonstrate the relevance of these definitions by highlighting applications from a single biological system (an amphibian–pathogen system) and discuss situations where the use of occupancy models has been criticized. Finally, we use these applications to suggest future research and model development.

Modeling multisystem biological risk in young adults: The Coronary Artery Risk Development in Young Adults Study.

PubMed

Seeman, Teresa; Gruenewald, Tara; Karlamangla, Arun; Sidney, Steve; Liu, Kiang; McEwen, Bruce; Schwartz, Joseph

2010-01-01

Although much prior research has focused on identifying the roles of major regulatory systems in health risks, the concept of allostatic load (AL) focuses on the importance of a more multisystems view of health risks. How best to operationalize allostatic load, however, remains the subject of some debate. We sought to test a hypothesized metafactor model of allostatic load composed of a number of biological system factors, and to investigate model invariance across sex and ethnicity. Biological data from 782 men and women, aged 32-47, from the Oakland, CA and Chicago, IL sites of the Coronary Artery Risk Development in Young Adults Study (CARDIA) were collected as part of the Year 15exam in 2000. These include measures of blood pressure, metabolic parameters (glucose, insulin, lipid profiles, and waist circumference), markers of inflammation (interleukin-6, C-reactive protein, and fibrinogen), heart rate variability, sympathetic nervous system activity (12-hr urinary norepinephrine and epinephrine) and hypothalamic-pituitary-adrenal axis activity (diurnal salivary free cortisol). A "metafactor" model of AL as an aggregate measure of six underlying latent biological subfactors was found to fit the data, with the metafactor structure capturing 84% of variance of all pairwise associations among biological subsystems. There was little evidence of model variance across sex and/or ethnicity. These analyses extend work operationalizing AL as a multisystems index of biological dysregulation, providing initial support for a model of AL as a metaconstruct of inter-relationships among multiple biological regulatory systems, that varies little across sex or ethnicity.

Circadian systems biology in Metazoa.

PubMed

Lin, Li-Ling; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

2015-11-01

Systems biology, which can be defined as integrative biology, comprises multistage processes that can be used to understand components of complex biological systems of living organisms and provides hierarchical information to decoding life. Using systems biology approaches such as genomics, transcriptomics and proteomics, it is now possible to delineate more complicated interactions between circadian control systems and diseases. The circadian rhythm is a multiscale phenomenon existing within the body that influences numerous physiological activities such as changes in gene expression, protein turnover, metabolism and human behavior. In this review, we describe the relationships between the circadian control system and its related genes or proteins, and circadian rhythm disorders in systems biology studies. To maintain and modulate circadian oscillation, cells possess elaborative feedback loops composed of circadian core proteins that regulate the expression of other genes through their transcriptional activities. The disruption of these rhythms has been reported to be associated with diseases such as arrhythmia, obesity, insulin resistance, carcinogenesis and disruptions in natural oscillations in the control of cell growth. This review demonstrates that lifestyle is considered as a fundamental factor that modifies circadian rhythm, and the development of dysfunctions and diseases could be regulated by an underlying expression network with multiple circadian-associated signals. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Systems biology driven software design for the research enterprise.

PubMed

Boyle, John; Cavnor, Christopher; Killcoyne, Sarah; Shmulevich, Ilya

2008-06-25

In systems biology, and many other areas of research, there is a need for the interoperability of tools and data sources that were not originally designed to be integrated. Due to the interdisciplinary nature of systems biology, and its association with high throughput experimental platforms, there is an additional need to continually integrate new technologies. As scientists work in isolated groups, integration with other groups is rarely a consideration when building the required software tools. We illustrate an approach, through the discussion of a purpose built software architecture, which allows disparate groups to reuse tools and access data sources in a common manner. The architecture allows for: the rapid development of distributed applications; interoperability, so it can be used by a wide variety of developers and computational biologists; development using standard tools, so that it is easy to maintain and does not require a large development effort; extensibility, so that new technologies and data types can be incorporated; and non intrusive development, insofar as researchers need not to adhere to a pre-existing object model. By using a relatively simple integration strategy, based upon a common identity system and dynamically discovered interoperable services, a light-weight software architecture can become the focal point through which scientists can both get access to and analyse the plethora of experimentally derived data.

New Tools & Techniques for the Metallomics Revolution

NASA Astrophysics Data System (ADS)

Koppenaal, D. W.; Hieftje, G. M.

2004-12-01

The metallome has been defined as the complete complement of metals and metal moieties in a biological cell, tissue, or system. This definition is akin to that of the genome (genes), proteome (proteins), and metabolome (metabolites). Metallomics accordingly is the study of metals and metal species, and their interactions, transformations, and functions in biological systems. While traditional bioinorganic chemistry has focused on the role and interactions of a single (or few) metals in a protein or enzyme system, metallomics purports to study global, multi-element interactions and relationships. The metallomics challenges for analytical chemistry and biochemical characterization are significant. This paper will discuss these challenges and the emergent techniques and tools that are being developed to address them. Mass spectrometry will play an important and pivotal role. Two approaches are currently being developed in the authors' laboratories. At Pacific Northwest National Laboratory, an extremely high-resolution approach using Fourier Transform Ion Cyclotron Resonance mass spectrometry (FT-ICRMS) is under development. At Indiana University, a rapid, dual-reflectron Time-of-Flight mass spectrometry (TOFMS) technique is being developed. Both approaches rely on dual inductively coupled plasma (ICP) and electrospray ionization (ESI) sources for elemental and biomolecular ion generation. The initial development of these techniques, and their potential application to systems biology and environmental characterization, will be discussed.

Advances in synthetic peptides reagent discovery

NASA Astrophysics Data System (ADS)

Adams, Bryn L.; Sarkes, Deborah A.; Finch, Amethist S.; Stratis-Cullum, Dimitra N.

2013-05-01

Bacterial display technology offers a number of advantages over competing display technologies (e.g, phage) for the rapid discovery and development of peptides with interaction targeted to materials ranging from biological hazards through inorganic metals. We have previously shown that discovery of synthetic peptide reagents utilizing bacterial display technology is relatively simple and rapid to make laboratory automation possible. This included extensive study of the protective antigen system of Bacillus anthracis, including development of discovery, characterization, and computational biology capabilities for in-silico optimization. Although the benefits towards CBD goals are evident, the impact is far-reaching due to our ability to understand and harness peptide interactions that are ultimately extendable to the hybrid biomaterials of the future. In this paper, we describe advances in peptide discovery including, new target systems (e.g. non-biological materials), advanced library development and clone analysis including integrated reporting.

Engineering biological systems toward a sustainable bioeconomy.

PubMed

Lopes, Mateus Schreiner Garcez

2015-06-01

The nature of our major global risks calls for sustainable innovations to decouple economic growth from greenhouse gases emission. The development of sustainable technologies has been negatively impacted by several factors including sugar production costs, production scale, economic crises, hydraulic fracking development and the market inability to capture externality costs. However, advances in engineering of biological systems allow bridging the gap between exponential growth of knowledge about biology and the creation of sustainable value chains for a broad range of economic sectors. Additionally, industrial symbiosis of different biobased technologies can increase competitiveness and sustainability, leading to the development of eco-industrial parks. Reliable policies for carbon pricing and revenue reinvestments in disruptive technologies and in the deployment of eco-industrial parks could boost the welfare while addressing our major global risks toward the transition from a fossil to a biobased economy.

Biocellion: accelerating computer simulation of multicellular biological system models

PubMed Central

Kang, Seunghwa; Kahan, Simon; McDermott, Jason; Flann, Nicholas; Shmulevich, Ilya

2014-01-01

Motivation: Biological system behaviors are often the outcome of complex interactions among a large number of cells and their biotic and abiotic environment. Computational biologists attempt to understand, predict and manipulate biological system behavior through mathematical modeling and computer simulation. Discrete agent-based modeling (in combination with high-resolution grids to model the extracellular environment) is a popular approach for building biological system models. However, the computational complexity of this approach forces computational biologists to resort to coarser resolution approaches to simulate large biological systems. High-performance parallel computers have the potential to address the computing challenge, but writing efficient software for parallel computers is difficult and time-consuming. Results: We have developed Biocellion, a high-performance software framework, to solve this computing challenge using parallel computers. To support a wide range of multicellular biological system models, Biocellion asks users to provide their model specifics by filling the function body of pre-defined model routines. Using Biocellion, modelers without parallel computing expertise can efficiently exploit parallel computers with less effort than writing sequential programs from scratch. We simulate cell sorting, microbial patterning and a bacterial system in soil aggregate as case studies. Availability and implementation: Biocellion runs on x86 compatible systems with the 64 bit Linux operating system and is freely available for academic use. Visit http://biocellion.com for additional information. Contact: seunghwa.kang@pnnl.gov PMID:25064572

Development and Deployment of Systems-Based Approaches for the Management of Soilborne Plant Pathogens.

PubMed

Chellemi, D O; Gamliel, A; Katan, J; Subbarao, K V

2016-03-01

Biological suppression of soilborne diseases with minimal use of outside interventive actions has been difficult to achieve in high input conventional crop production systems due to the inherent risk of pest resurgence. This review examines previous approaches to the management of soilborne disease as precursors to the evolution of a systems-based approach, in which plant disease suppression through natural biological feedback mechanisms in soil is incorporated into the design and operation of cropping systems. Two case studies are provided as examples in which a systems-based approach is being developed and deployed in the production of high value crops: lettuce/strawberry production in the coastal valleys of central California (United States) and sweet basil and other herb crop production in Israel. Considerations for developing and deploying system-based approaches are discussed and operational frameworks and metrics to guide their development are presented with the goal of offering a credible alternative to conventional approaches to soilborne disease management.

Theoretical aspects of Systems Biology.

PubMed

Bizzarri, Mariano; Palombo, Alessandro; Cucina, Alessandra

2013-05-01

The natural world consists of hierarchical levels of complexity that range from subatomic particles and molecules to ecosystems and beyond. This implies that, in order to explain the features and behavior of a whole system, a theory might be required that would operate at the corresponding hierarchical level, i.e. where self-organization processes take place. In the past, biological research has focused on questions that could be answered by a reductionist program of genetics. The organism (and its development) was considered an epiphenomenona of its genes. However, a profound rethinking of the biological paradigm is now underway and it is likely that such a process will lead to a conceptual revolution emerging from the ashes of reductionism. This revolution implies the search for general principles on which a cogent theory of biology might rely. Because much of the logic of living systems is located at higher levels, it is imperative to focus on them. Indeed, both evolution and physiology work on these levels. Thus, by no means Systems Biology could be considered a 'simple' 'gradual' extension of Molecular Biology. Copyright © 2013 Elsevier Ltd. All rights reserved.

A mathematical applications into the cells.

PubMed

Tiwari, Manjul

2012-01-01

Biology has become the new "physics" of mathematics, one of the areas of greatest mathematical applications. In turn, mathematics has provided powerful tools and metaphors to approach the astonishing complexity of biological systems. This has allowed the development of sound theoretical frameworks. Here, in this review article, some of the most significant contributions of mathematics to biology, ranging from population genetics, to developmental biology, and to networks of species interactions are summarized.

Plant biology in space: proceedings of the International Workshop, Bad Honnef, Germany, June 24-27, 1996

NASA Technical Reports Server (NTRS)

Scott, T. K. (Principal Investigator)

1997-01-01

Papers presented at the International Workshop on Plant Biology in Space include reviews, reports, and perspectives related to plant gravitational biology. Presentations focused on nine subject areas: gravitropism in unicellular plants, gravitropism in fungi, cell development, gravity perception in multicellular plants, gravity responses in multicellular plants, plant reproduction, evaluation of a clinostat for weightlessness simulation, biological life support systems, and future research.

Strategies for structuring interdisciplinary education in Systems Biology: an European perspective

PubMed Central

Cvijovic, Marija; Höfer, Thomas; Aćimović, Jure; Alberghina, Lilia; Almaas, Eivind; Besozzi, Daniela; Blomberg, Anders; Bretschneider, Till; Cascante, Marta; Collin, Olivier; de Atauri, Pedro; Depner, Cornelia; Dickinson, Robert; Dobrzynski, Maciej; Fleck, Christian; Garcia-Ojalvo, Jordi; Gonze, Didier; Hahn, Jens; Hess, Heide Marie; Hollmann, Susanne; Krantz, Marcus; Kummer, Ursula; Lundh, Torbjörn; Martial, Gifta; dos Santos, Vítor Martins; Mauer-Oberthür, Angela; Regierer, Babette; Skene, Barbara; Stalidzans, Egils; Stelling, Jörg; Teusink, Bas; Workman, Christopher T; Hohmann, Stefan

2016-01-01

Systems Biology is an approach to biology and medicine that has the potential to lead to a better understanding of how biological properties emerge from the interaction of genes, proteins, molecules, cells and organisms. The approach aims at elucidating how these interactions govern biological function by employing experimental data, mathematical models and computational simulations. As Systems Biology is inherently multidisciplinary, education within this field meets numerous hurdles including departmental barriers, availability of all required expertise locally, appropriate teaching material and example curricula. As university education at the Bachelor’s level is traditionally built upon disciplinary degrees, we believe that the most effective way to implement education in Systems Biology would be at the Master’s level, as it offers a more flexible framework. Our team of experts and active performers of Systems Biology education suggest here (i) a definition of the skills that students should acquire within a Master’s programme in Systems Biology, (ii) a possible basic educational curriculum with flexibility to adjust to different application areas and local research strengths, (iii) a description of possible career paths for students who undergo such an education, (iv) conditions that should improve the recruitment of students to such programmes and (v) mechanisms for collaboration and excellence spreading among education professionals. With the growing interest of industry in applying Systems Biology approaches in their fields, a concerted action between academia and industry is needed to build this expertise. Here we present a reflection of the European situation and expertise, where most of the challenges we discuss are universal, anticipating that our suggestions will be useful internationally. We believe that one of the overriding goals of any Systems Biology education should be a student’s ability to phrase and communicate research questions in such a manner that they can be solved by the integration of experiments and modelling, as well as to communicate and collaborate productively across different experimental and theoretical disciplines in research and development. PMID:28725471

Biological stress systems, adverse life events and the onset of chronic multisite musculoskeletal pain: a 6-year cohort study.

PubMed

Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; de Geus, Eco J C N; Penninx, Brenda W J H; Dekker, Joost

2016-05-01

Dysregulated biological stress systems and adverse life events, independently and in interaction, have been hypothesised to initiate chronic pain. We examine whether (1) function of biological stress systems, (2) adverse life events, and (3) their combination predict the onset of chronic multisite musculoskeletal pain. Subjects (n=2039) of the Netherlands Study of Depression and Anxiety, free from chronic multisite musculoskeletal pain at baseline, were identified using the Chronic Pain Grade Questionnaire and followed up for the onset of chronic multisite musculoskeletal pain over 6 years. Baseline assessment of biological stress systems comprised function of the hypothalamic-pituitary-adrenal axis (1-h cortisol awakening response, evening levels, postdexamethasone levels), the immune system (basal and lipopolysaccharide-stimulated inflammation) and the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, respiratory sinus arrhythmia). The number of recent adverse life events was assessed at baseline using the List of Threatening Events Questionnaire. Hypothalamic-pituitary-adrenal axis, immune system and autonomic nervous system functioning was not associated with onset of chronic multisite musculoskeletal pain, either by itself or in interaction with adverse life events. Adverse life events did predict onset of chronic multisite musculoskeletal pain (HR per event=1.14, 95% CI 1.04 to 1.24, p=0.005). This longitudinal study could not confirm that dysregulated biological stress systems increase the risk of developing chronic multisite musculoskeletal pain. Adverse life events were a risk factor for the onset of chronic multisite musculoskeletal pain, suggesting that psychosocial factors play a role in triggering the development of this condition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Biomarkers for Uranium Risk Assessment for the Development of the CURE (Concerted Uranium Research in Europe) Molecular Epidemiological Protocol.

PubMed

Guéguen, Yann; Roy, Laurence; Hornhardt, Sabine; Badie, Christophe; Hall, Janet; Baatout, Sarah; Pernot, Eileen; Tomasek, Ladislav; Laurent, Olivier; Ebrahimian, Teni; Ibanez, Chrystelle; Grison, Stephane; Kabacik, Sylwia; Laurier, Dominique; Gomolka, Maria

2017-01-01

Despite substantial experimental and epidemiological research, there is limited knowledge of the uranium-induce health effects after chronic low-dose exposures in humans. Biological markers can objectively characterize pathological processes or environmental responses to uranium and confounding agents. The integration of such biological markers into a molecular epidemiological study would be a useful approach to improve and refine estimations of uranium-induced health risks. To initiate such a study, Concerted Uranium Research in Europe (CURE) was established, and involves biologists, epidemiologists and dosimetrists. The aims of the biological work package of CURE were: 1. To identify biomarkers and biological specimens relevant to uranium exposure; 2. To define standard operating procedures (SOPs); and 3. To set up a common protocol (logistic, questionnaire, ethical aspects) to perform a large-scale molecular epidemiologic study in uranium-exposed cohorts. An intensive literature review was performed and led to the identification of biomarkers related to: 1. retention organs (lungs, kidneys and bone); 2. other systems/organs with suspected effects (cardiovascular system, central nervous system and lympho-hematopoietic system); 3. target molecules (DNA damage, genomic instability); and 4. high-throughput methods for the identification of new biomarkers. To obtain high-quality biological materials, SOPs were established for the sampling and storage of different biospecimens. A questionnaire was developed to assess potential confounding factors. The proposed strategy can be adapted to other internal exposures and should improve the characterization of the biological and health effects that are relevant for risk assessment.

Technology development for lunar base water recycling

NASA Technical Reports Server (NTRS)

Schultz, John R.; Sauer, Richard L.

1992-01-01

This paper will review previous and ongoing work in aerospace water recycling and identify research activities required to support development of a lunar base. The development of a water recycle system for use in the life support systems envisioned for a lunar base will require considerable research work. A review of previous work on aerospace water recycle systems indicates that more efficient physical and chemical processes are needed to reduce expendable and power requirements. Development work on biological processes that can be applied to microgravity and lunar environments also needs to be initiated. Biological processes are inherently more efficient than physical and chemical processes and may be used to minimize resupply and waste disposal requirements. Processes for recovering and recycling nutrients such as nitrogen, phosphorus, and sulfur also need to be developed to support plant growth units. The development of efficient water quality monitors to be used for process control and environmental monitoring also needs to be initiated.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shimizu, Y; Yoon, Y; Iwase, K

Purpose: We are trying to develop an image-searching technique to identify misfiled images in a picture archiving and communication system (PACS) server by using five biological fingerprints: the whole lung field, cardiac shadow, superior mediastinum, lung apex, and right lower lung. Each biological fingerprint in a chest radiograph includes distinctive anatomical structures to identify misfiled images. The whole lung field was less effective for evaluating the similarity between two images than the other biological fingerprints. This was mainly due to the variation in the positioning for chest radiographs. The purpose of this study is to develop new biological fingerprints thatmore » could reduce influence of differences in the positioning for chest radiography. Methods: Two hundred patients were selected randomly from our database (36,212 patients). These patients had two images each (current and previous images). Current images were used as the misfiled images in this study. A circumscribed rectangular area of the lung and the upper half of the rectangle were selected automatically as new biological fingerprints. These biological fingerprints were matched to all previous images in the database. The degrees of similarity between the two images were calculated for the same and different patients. The usefulness of new the biological fingerprints for automated patient recognition was examined in terms of receiver operating characteristic (ROC) analysis. Results: Area under the ROC curves (AUCs) for the circumscribed rectangle of the lung, upper half of the rectangle, and whole lung field were 0.980, 0.994, and 0.950, respectively. The new biological fingerprints showed better performance in identifying the patients correctly than the whole lung field. Conclusion: We have developed new biological fingerprints: circumscribed rectangle of the lung and upper half of the rectangle. These new biological fingerprints would be useful for automated patient identification system because they are less affected by positioning differences during imaging.« less

Systems biology of personalized nutrition

PubMed Central

van Ommen, Ben; van den Broek, Tim; de Hoogh, Iris; van Erk, Marjan; van Someren, Eugene; Rouhani-Rankouhi, Tanja; Anthony, Joshua C; Hogenelst, Koen; Pasman, Wilrike; Boorsma, André; Wopereis, Suzan

2017-01-01

Abstract Personalized nutrition is fast becoming a reality due to a number of technological, scientific, and societal developments that complement and extend current public health nutrition recommendations. Personalized nutrition tailors dietary recommendations to specific biological requirements on the basis of a person’s health status and goals. The biology underpinning these recommendations is complex, and thus any recommendations must account for multiple biological processes and subprocesses occurring in various tissues and must be formed with an appreciation for how these processes interact with dietary nutrients and environmental factors. Therefore, a systems biology–based approach that considers the most relevant interacting biological mechanisms is necessary to formulate the best recommendations to help people meet their wellness goals. Here, the concept of “systems flexibility” is introduced to personalized nutrition biology. Systems flexibility allows the real-time evaluation of metabolism and other processes that maintain homeostasis following an environmental challenge, thereby enabling the formulation of personalized recommendations. Examples in the area of macro- and micronutrients are reviewed. Genetic variations and performance goals are integrated into this systems approach to provide a strategy for a balanced evaluation and an introduction to personalized nutrition. Finally, modeling approaches that combine personalized diagnosis and nutritional intervention into practice are reviewed. PMID:28969366

Growing trend of CE at the omics level: the frontier of systems biology.

PubMed

Oh, Eulsik; Hasan, Md Nabiul; Jamshed, Muhammad; Park, Soo Hyun; Hong, Hye-Min; Song, Eun Joo; Yoo, Young Sook

2010-01-01

In a novel attempt to comprehend the complexity of life, systems biology has recently emerged as a state-of-the-art approach for biological research in contrast to the reductionist approaches that have been used in molecular cell biology since the 1950s. Because a massive amount of information is required in many systems biology studies of life processes, we have increasingly come to depend on techniques that provide high-throughput omics data. CE and CE coupled to MS have served as powerful analytical tools for providing qualitative and quantitative omics data. Recent systems biology studies have focused strongly on the diagnosis and treatment of diseases. The increasing number of clinical research papers on drug discovery and disease therapies reflects this growing interest among scientists. Since such clinical research reflects one of the ultimate purposes of bioscience, these trends will be sustained for a long time. Thus, this review mainly focuses on the application of CE and CE-MS in diagnosis as well as on the latest CE methods developed. Furthermore, we outline the new challenges that arose in 2008 and later in elucidating the system-level functions of the bioconstituents of living organisms.

Challenges and opportunities in synthetic biology for chemical engineers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, YZ; Lee, JK; Zhao, HM

Synthetic biology provides numerous great opportunities for chemical engineers in the development of new processes for large-scale production of biofuels, value-added chemicals, and protein therapeutics. However, challenges across all scales abound. In particular, the modularization and standardization of the components in a biological system, so-called biological parts, remain the biggest obstacle in synthetic biology. In this perspective, we will discuss the main challenges and opportunities in the rapidly growing synthetic biology field and the important roles that chemical engineers can play in its advancement. (C) 2012 Elsevier Ltd. All rights reserved.

Challenges and opportunities in synthetic biology for chemical engineers

PubMed Central

Luo, Yunzi; Lee, Jung-Kul; Zhao, Huimin

2012-01-01

Synthetic biology provides numerous great opportunities for chemical engineers in the development of new processes for large-scale production of biofuels, value-added chemicals, and protein therapeutics. However, challenges across all scales abound. In particular, the modularization and standardization of the components in a biological system, so-called biological parts, remain the biggest obstacle in synthetic biology. In this perspective, we will discuss the main challenges and opportunities in the rapidly growing synthetic biology field and the important roles that chemical engineers can play in its advancement. PMID:24222925

Challenges and opportunities in synthetic biology for chemical engineers.

PubMed

Luo, Yunzi; Lee, Jung-Kul; Zhao, Huimin

2013-11-15

Synthetic biology provides numerous great opportunities for chemical engineers in the development of new processes for large-scale production of biofuels, value-added chemicals, and protein therapeutics. However, challenges across all scales abound. In particular, the modularization and standardization of the components in a biological system, so-called biological parts, remain the biggest obstacle in synthetic biology. In this perspective, we will discuss the main challenges and opportunities in the rapidly growing synthetic biology field and the important roles that chemical engineers can play in its advancement.

Mass balances for a biological life support system simulation model

NASA Technical Reports Server (NTRS)

Volk, Tyler; Rummel, John D.

1987-01-01

Design decisions to aid the development of future space based biological life support systems (BLSS) can be made with simulation models. The biochemistry stoichiometry was developed for: (1) protein, carbohydrate, fat, fiber, and lignin production in the edible and inedible parts of plants; (2) food consumption and production of organic solids in urine, feces, and wash water by the humans; and (3) operation of the waste processor. Flux values for all components are derived for a steady state system with wheat as the sole food source. The large scale dynamics of a materially closed (BLSS) computer model is described in a companion paper. An extension of this methodology can explore multifood systems and more complex biochemical dynamics while maintaining whole system closure as a focus.

Computational approaches to metabolic engineering utilizing systems biology and synthetic biology.

PubMed

Fong, Stephen S

2014-08-01

Metabolic engineering modifies cellular function to address various biochemical applications. Underlying metabolic engineering efforts are a host of tools and knowledge that are integrated to enable successful outcomes. Concurrent development of computational and experimental tools has enabled different approaches to metabolic engineering. One approach is to leverage knowledge and computational tools to prospectively predict designs to achieve the desired outcome. An alternative approach is to utilize combinatorial experimental tools to empirically explore the range of cellular function and to screen for desired traits. This mini-review focuses on computational systems biology and synthetic biology tools that can be used in combination for prospective in silico strain design.

Biological indicators for monitoring water quality of MTF canals system

NASA Technical Reports Server (NTRS)

Sethi, S. L.

1975-01-01

Biological models, diversity indexes, were developed to predict environmental effects of NASA's Mississippi test facility (MTF) chemical operations on canal systems in the area. To predict the effects on local streams, a physical model of unpolluted streams was established. The model is fed by artesian well water free of background levels of pollutants. The species diversity and biota composition of unpolluted MTF stream was determined; resulting information will be used to form baseline data for future comparisons. Biological modeling was accomplished by adding controlled quantities or kinds of chemical pollutants and evaluating the effects of these chemicals on the biological life of the stream.

Biological issues in materials science and engineering: Interdisciplinarity and the bio-materials paradigm

NASA Astrophysics Data System (ADS)

Murr, L. E.

2006-07-01

Biological systems and processes have had, and continue to have, important implications and applications in materials extraction, processing, and performance. This paper illustrates some interdisciplinary, biological issues in materials science and engineering. These include metal extraction involving bacterial catalysis, galvanic couples, bacterial-assisted corrosion and degradation of materials, biosorption and bioremediation of toxic and other heavy metals, metal and material implants and prostheses and related dental and medical biomaterials developments and applications, nanomaterials health benefits and toxicity issue, and biomimetics and biologically inspired materials developments. These and other examples provide compelling evidence and arguments for emphasizing biological sicences in materials science and engineering curricula and the implementation of a bio-materials paradigm to facilitate the emergence of innovative interdisciplinarity involving the biological sciences and materials sciences and engineering.

Understanding system dynamics of an adaptive enzyme network from globally profiled kinetic parameters.

PubMed

Chiang, Austin W T; Liu, Wei-Chung; Charusanti, Pep; Hwang, Ming-Jing

2014-01-15

A major challenge in mathematical modeling of biological systems is to determine how model parameters contribute to systems dynamics. As biological processes are often complex in nature, it is desirable to address this issue using a systematic approach. Here, we propose a simple methodology that first performs an enrichment test to find patterns in the values of globally profiled kinetic parameters with which a model can produce the required system dynamics; this is then followed by a statistical test to elucidate the association between individual parameters and different parts of the system's dynamics. We demonstrate our methodology on a prototype biological system of perfect adaptation dynamics, namely the chemotaxis model for Escherichia coli. Our results agreed well with those derived from experimental data and theoretical studies in the literature. Using this model system, we showed that there are motifs in kinetic parameters and that these motifs are governed by constraints of the specified system dynamics. A systematic approach based on enrichment statistical tests has been developed to elucidate the relationships between model parameters and the roles they play in affecting system dynamics of a prototype biological network. The proposed approach is generally applicable and therefore can find wide use in systems biology modeling research.

Synthetic Biology for Therapeutic Applications

PubMed Central

2015-01-01

Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders. PMID:25098838

Synthetic Biology for Therapeutic Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abil, Zhanar; Xiong, Xiong; Zhao, Huimin

Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders.

Synthetic Biology for Therapeutic Applications

DOE PAGES

Abil, Zhanar; Xiong, Xiong; Zhao, Huimin

2014-08-06

Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders.

Using Petri Net Tools to Study Properties and Dynamics of Biological Systems

PubMed Central

Peleg, Mor; Rubin, Daniel; Altman, Russ B.

2005-01-01

Petri Nets (PNs) and their extensions are promising methods for modeling and simulating biological systems. We surveyed PN formalisms and tools and compared them based on their mathematical capabilities as well as by their appropriateness to represent typical biological processes. We measured the ability of these tools to model specific features of biological systems and answer a set of biological questions that we defined. We found that different tools are required to provide all capabilities that we assessed. We created software to translate a generic PN model into most of the formalisms and tools discussed. We have also made available three models and suggest that a library of such models would catalyze progress in qualitative modeling via PNs. Development and wide adoption of common formats would enable researchers to share models and use different tools to analyze them without the need to convert to proprietary formats. PMID:15561791

Predictive ecology: systems approaches

PubMed Central

Evans, Matthew R.; Norris, Ken J.; Benton, Tim G.

2012-01-01

The world is experiencing significant, largely anthropogenically induced, environmental change. This will impact on the biological world and we need to be able to forecast its effects. In order to produce such forecasts, ecology needs to become more predictive—to develop the ability to understand how ecological systems will behave in future, changed, conditions. Further development of process-based models is required to allow such predictions to be made. Critical to the development of such models will be achieving a balance between the brute-force approach that naively attempts to include everything, and over simplification that throws out important heterogeneities at various levels. Central to this will be the recognition that individuals are the elementary particles of all ecological systems. As such it will be necessary to understand the effect of evolution on ecological systems, particularly when exposed to environmental change. However, insights from evolutionary biology will help the development of models even when data may be sparse. Process-based models are more common, and are used for forecasting, in other disciplines, e.g. climatology and molecular systems biology. Tools and techniques developed in these endeavours can be appropriated into ecological modelling, but it will also be necessary to develop the science of ecoinformatics along with approaches specific to ecological problems. The impetus for this effort should come from the demand coming from society to understand the effects of environmental change on the world and what might be performed to mitigate or adapt to them. PMID:22144379

Building biological foundries for next-generation synthetic biology.

PubMed

Chao, Ran; Yuan, YongBo; Zhao, HuiMin

2015-07-01

Synthetic biology is an interdisciplinary field that takes top-down approaches to understand and engineer biological systems through design-build-test cycles. A number of advances in this relatively young field have greatly accelerated such engineering cycles. Specifically, various innovative tools were developed for in silico biosystems design, DNA de novo synthesis and assembly, construct verification, as well as metabolite analysis, which have laid a solid foundation for building biological foundries for rapid prototyping of improved or novel biosystems. This review summarizes the state-of-the-art technologies for synthetic biology and discusses the challenges to establish such biological foundries.

Co-culture systems and technologies: taking synthetic biology to the next level

PubMed Central

Goers, Lisa; Freemont, Paul; Polizzi, Karen M.

2014-01-01

Co-culture techniques find myriad applications in biology for studying natural or synthetic interactions between cell populations. Such techniques are of great importance in synthetic biology, as multi-species cell consortia and other natural or synthetic ecology systems are widely seen to hold enormous potential for foundational research as well as novel industrial, medical and environmental applications with many proof-of-principle studies in recent years. What is needed for co-cultures to fulfil their potential? Cell–cell interactions in co-cultures are strongly influenced by the extracellular environment, which is determined by the experimental set-up, which therefore needs to be given careful consideration. An overview of existing experimental and theoretical co-culture set-ups in synthetic biology and adjacent fields is given here, and challenges and opportunities involved in such experiments are discussed. Greater focus on foundational technology developments for co-cultures is needed for many synthetic biology systems to realize their potential in both applications and answering biological questions. PMID:24829281

Federal Research and Development Funding: FY2010

DTIC Science & Technology

2009-12-24

weapon systems or components (e.g., the Joint Strike Fighter or missile defense systems), for which an operational need has been determined and an...million to the S&T Directorate to fund developmental testing of the BioWatch Generation 3 biological agent detection system. The Administration requested...142 142 143 143 R&D, Acquisition, and Operations 800 826 825 844 856 Border and Maritime 33 40 40 40 44 Chemical and Biological 200 207 222 207

New applications in EPA’s ECOTOX Knowledge System: Assimilating relative potencies of metals across chemical and biological species from literature-based toxicity effects data.

EPA Science Inventory

Toxicity of metals in field settings can vary widely among ionic chemical species and across biological receptors. Thus, a challenge often found in developing TRVs for the risk assessment of metals is identifying the most appropriate metal and biological species combinations for...

Exploring the MACH Model's Potential as a Metacognitive Tool to Help Undergraduate Students Monitor Their Explanations of Biological Mechanisms

ERIC Educational Resources Information Center

Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

2016-01-01

When undergraduate biology students learn to explain biological mechanisms, they face many challenges and may overestimate their understanding of living systems. Previously, we developed the MACH model of four components used by expert biologists to explain mechanisms: Methods, Analogies, Context, and How. This study explores the implementation of…

Monitoring of environmental UV radiation by biological dosimeters

NASA Astrophysics Data System (ADS)

Rontó, Gy.; Bérces, A.; Gróf, P.; Fekete, A.; Kerékgyártó, T.; Gáspár, S.; Stick, C.

As a consequence of the stratospheric ozone layer depletion biological systems can be damaged due to increased UV-B radiation. The aim of biological dosimetry is to establish a quantitative basis for the risk assessment of the biosphere. DNA is the most important target molecule of biological systems having special sensitivity against short wavelength components of the environmental radiation. Biological dosimeters are usually simple organisms, or components of them, modeling the cellular DNA. Phage T7 and polycrystalline uracil biological dosimeters have been developed and used in our laboratory for monitoring the environmental radiation in different radiation conditions (from the polar to equatorial regions). Comparisons with Robertson-Berger (RB) meter data, as well as with model calculation data weighted by the corresponding spectral sensitivities of the dosimeters are presented. Suggestion is given how to determine the trend of the increase in the biological risk due to ozone depletion.

Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation.

PubMed

Shinde, Vaibhav; Klima, Stefanie; Sureshkumar, Perumal Srinivasan; Meganathan, Kesavan; Jagtap, Smita; Rempel, Eugen; Rahnenführer, Jörg; Hengstler, Jan Georg; Waldmann, Tanja; Hescheler, Jürgen; Leist, Marcel; Sachinidis, Agapios

2015-06-17

Efficient protocols to differentiate human pluripotent stem cells to various tissues in combination with -omics technologies opened up new horizons for in vitro toxicity testing of potential drugs. To provide a solid scientific basis for such assays, it will be important to gain quantitative information on the time course of development and on the underlying regulatory mechanisms by systems biology approaches. Two assays have therefore been tuned here for these requirements. In the UKK test system, human embryonic stem cells (hESC) (or other pluripotent cells) are left to spontaneously differentiate for 14 days in embryoid bodies, to allow generation of cells of all three germ layers. This system recapitulates key steps of early human embryonic development, and it can predict human-specific early embryonic toxicity/teratogenicity, if cells are exposed to chemicals during differentiation. The UKN1 test system is based on hESC differentiating to a population of neuroectodermal progenitor (NEP) cells for 6 days. This system recapitulates early neural development and predicts early developmental neurotoxicity and epigenetic changes triggered by chemicals. Both systems, in combination with transcriptome microarray studies, are suitable for identifying toxicity biomarkers. Moreover, they may be used in combination to generate input data for systems biology analysis. These test systems have advantages over the traditional toxicological studies requiring large amounts of animals. The test systems may contribute to a reduction of the costs for drug development and chemical safety evaluation. Their combination sheds light especially on compounds that may influence neurodevelopment specifically.

CINRG: Systems Biology of Glucocorticoids in Muscle Disease

DTIC Science & Technology

2013-10-01

Contract W81XWH-09-1-0726 SYSTEMS BIOLOGY OF GLUCOCORTICOIDS IN MUSCLE DISEASE Introduction Duchenne muscular dystrophy (DMD) is the most...common and incurable muscular dystrophy of childhood. Muscle regeneration fails with advancing age, leading to considerable fibrosis. Corticosteroid... muscle and enable the development of better targeted and more effective therapies for Duchenne muscular dystrophy dynamically. This MDA grant

Thiol/disulfide redox states in signaling and sensing

PubMed Central

Go, Young-Mi; Jones, Dean P.

2015-01-01

Rapid advances in redox systems biology are creating new opportunities to understand complexities of human disease and contributions of environmental exposures. New understanding of thiol-disulfide systems have occurred during the past decade as a consequence of the discoveries that thiol and disulfide systems are maintained in kinetically controlled steady-states displaced from thermodynamic equilibrium, that a widely distributed family of NADPH oxidases produces oxidants that function in cell signaling, and that a family of peroxiredoxins utilize thioredoxin as a reductant to complement the well-studied glutathione antioxidant system for peroxide elimination and redox regulation. This review focuses on thiol/disulfide redox state in biologic systems and the knowledge base available to support development of integrated redox systems biology models to better understand the function and dysfunction of thiol-disulfide redox systems. In particular, central principles have emerged concerning redox compartmentalization and utility of thiol/disulfide redox measures as indicators of physiologic function. Advances in redox proteomics show that, in addition to functioning in protein active sites and cell signaling, cysteine residues also serve as redox sensors to integrate biologic functions. These advances provide a framework for translation of redox systems biology concepts to practical use in understanding and treating human disease. Biological responses to cadmium, a widespread environmental agent, are used to illustrate the utility of these advances to the understanding of complex pleiotropic toxicities. PMID:23356510

The dilemma of dual use biological research: Polish perspective.

PubMed

Czarkowski, Marek

2010-03-01

Biological research with legitimate scientific purpose that may be misused to pose a biological threat to public health and/or national security is termed dual use. In Poland there are adequate conditions for conducting experiments that could be qualified as dual use research, and therefore, a risk of attack on Poland or other countries exists. Optimal solutions for limiting such threats are required, and the national system of biosecurity should enable early, reliable, and complete identification of this type of research. Scientists should have a fundamental role in this process, their duty being to immediately, upon identification, report research with dual use potential. An important entity in the identification system of dual use research should also be the Central Register of Biological and Biomedical Research, which gathers information about all biological and biomedical research being conducted in a given country. Publishers, editors, and review committees of journals and other scientific publications should be involved in evaluating results of clinical trials. The National Council of Biosecurity should be the governmental institution responsible for developing a system of dual use research threat prevention. Its role would be to develop codes of conduct, form counsel of expertise, and monitor the problem at national level, while the Dual Use Research Committee would be responsible for individual cases. In Poland, current actions aiming to provide biological safety were based on developing and passing an act about genetically modified organisms (GMO's) and creating a GMO Committee. Considering experiences of other nations, one should view these actions as fragmentary, and thus insufficient protection against dual use research threats.

The role of low-grade inflammation and metabolic flexibility in aging and nutritional modulation thereof: a systems biology approach.

PubMed

Calçada, Dulce; Vianello, Dario; Giampieri, Enrico; Sala, Claudia; Castellani, Gastone; de Graaf, Albert; Kremer, Bas; van Ommen, Ben; Feskens, Edith; Santoro, Aurelia; Franceschi, Claudio; Bouwman, Jildau

2014-01-01

Aging is a biological process characterized by the progressive functional decline of many interrelated physiological systems. In particular, aging is associated with the development of a systemic state of low-grade chronic inflammation (inflammaging), and with progressive deterioration of metabolic function. Systems biology has helped in identifying the mediators and pathways involved in these phenomena, mainly through the application of high-throughput screening methods, valued for their molecular comprehensiveness. Nevertheless, inflammation and metabolic regulation are dynamical processes whose behavior must be understood at multiple levels of biological organization (molecular, cellular, organ, and system levels) and on multiple time scales. Mathematical modeling of such behavior, with incorporation of mechanistic knowledge on interactions between inflammatory and metabolic mediators, may help in devising nutritional interventions capable of preventing, or ameliorating, the age-associated functional decline of the corresponding systems. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

A review of selected pumping systems in nature and engineering--potential biomimetic concepts for improving displacement pumps and pulsation damping.

PubMed

Bach, D; Schmich, F; Masselter, T; Speck, T

2015-09-03

The active transport of fluids by pumps plays an essential role in engineering and biology. Due to increasing energy costs and environmental issues, topics like noise reduction, increase of efficiency and enhanced robustness are of high importance in the development of pumps in engineering. The study compares pumps in biology and engineering and assesses biomimetic potentials for improving man-made pumping systems. To this aim, examples of common challenges, applications and current biomimetic research for state-of-the art pumps are presented. The biomimetic research is helped by the similar configuration of many positive displacement pumping systems in biology and engineering. In contrast, the configuration and underlying pumping principles for fluid dynamic pumps (FDPs) differ to a greater extent in biology and engineering. However, progress has been made for positive displacement as well as for FDPs by developing biomimetic devices with artificial muscles and cilia that improve energetic efficiency and fail-safe operation or reduce noise. The circulatory system of vertebrates holds a high biomimetic potential for the damping of pressure pulsations, a common challenge in engineering. Damping of blood pressure pulsation results from a nonlinear viscoelastic behavior of the artery walls which represent a complex composite material. The transfer of the underlying functional principle could lead to an improvement of existing technical solutions and be used to develop novel biomimetic damping solutions. To enhance efficiency or thrust of man-made fluid transportation systems, research on jet propulsion in biology has shown that a pulsed jet can be tuned to either maximize thrust or efficiency. The underlying principle has already been transferred into biomimetic applications in open channel water systems. Overall there is a high potential to learn from nature in order to improve pumping systems for challenges like the reduction of pressure pulsations, increase of jet propulsion efficiency or the reduction of wear.

Statistical Techniques Complement UML When Developing Domain Models of Complex Dynamical Biosystems.

PubMed

Williams, Richard A; Timmis, Jon; Qwarnstrom, Eva E

2016-01-01

Computational modelling and simulation is increasingly being used to complement traditional wet-lab techniques when investigating the mechanistic behaviours of complex biological systems. In order to ensure computational models are fit for purpose, it is essential that the abstracted view of biology captured in the computational model, is clearly and unambiguously defined within a conceptual model of the biological domain (a domain model), that acts to accurately represent the biological system and to document the functional requirements for the resultant computational model. We present a domain model of the IL-1 stimulated NF-κB signalling pathway, which unambiguously defines the spatial, temporal and stochastic requirements for our future computational model. Through the development of this model, we observe that, in isolation, UML is not sufficient for the purpose of creating a domain model, and that a number of descriptive and multivariate statistical techniques provide complementary perspectives, in particular when modelling the heterogeneity of dynamics at the single-cell level. We believe this approach of using UML to define the structure and interactions within a complex system, along with statistics to define the stochastic and dynamic nature of complex systems, is crucial for ensuring that conceptual models of complex dynamical biosystems, which are developed using UML, are fit for purpose, and unambiguously define the functional requirements for the resultant computational model.

Statistical Techniques Complement UML When Developing Domain Models of Complex Dynamical Biosystems

PubMed Central

Timmis, Jon; Qwarnstrom, Eva E.

2016-01-01

Computational modelling and simulation is increasingly being used to complement traditional wet-lab techniques when investigating the mechanistic behaviours of complex biological systems. In order to ensure computational models are fit for purpose, it is essential that the abstracted view of biology captured in the computational model, is clearly and unambiguously defined within a conceptual model of the biological domain (a domain model), that acts to accurately represent the biological system and to document the functional requirements for the resultant computational model. We present a domain model of the IL-1 stimulated NF-κB signalling pathway, which unambiguously defines the spatial, temporal and stochastic requirements for our future computational model. Through the development of this model, we observe that, in isolation, UML is not sufficient for the purpose of creating a domain model, and that a number of descriptive and multivariate statistical techniques provide complementary perspectives, in particular when modelling the heterogeneity of dynamics at the single-cell level. We believe this approach of using UML to define the structure and interactions within a complex system, along with statistics to define the stochastic and dynamic nature of complex systems, is crucial for ensuring that conceptual models of complex dynamical biosystems, which are developed using UML, are fit for purpose, and unambiguously define the functional requirements for the resultant computational model. PMID:27571414

Convolving engineering and medical pedagogies for training of tomorrow's health care professionals.

PubMed

Lee, Raphael C

2013-03-01

Several fundamental benefits justify why biomedical engineering and medicine should form a more convergent alliance, especially for the training of tomorrow's physicians and biomedical engineers. Herein, we review the rationale underlying the benefits. Biological discovery has advanced beyond the era of molecular biology well into today's era of molecular systems biology, which focuses on understanding the rules that govern the behavior of complex living systems. This has important medical implications. To realize cost-effective personalized medicine, it is necessary to translate the advances in molecular systems biology to higher levels of biological organization (organ, system, and organismal levels) and then to develop new medical therapeutics based on simulation and medical informatics analysis. Higher education in biological and medical sciences must adapt to a new set of training objectives. This will involve a shifting away from reductionist problem solving toward more integrative, continuum, and predictive modeling approaches which traditionally have been more associated with engineering science. Future biomedical engineers and MDs must be able to predict clinical response to therapeutic intervention. Medical education will involve engineering pedagogies, wherein basic governing rules of complex system behavior and skill sets in manipulating these systems to achieve a practical desired outcome are taught. Similarly, graduate biomedical engineering programs will include more practical exposure to clinical problem solving.

Interspecies Systems Biology Uncovers Metabolites Affecting C. elegans Gene Expression and Life History Traits

PubMed Central

Watson, Emma; MacNeil, Lesley T.; Ritter, Ashlyn D.; Yilmaz, L. Safak; Rosebrock, Adam P.; Caudy, Amy A.; Walhout, Albertha J. M.

2014-01-01

SUMMARY Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here we used an interspecies systems biology approach with Caenorhabditis elegans and two if its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal’s gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development and reduces fertility, but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology. PMID:24529378

Hypothermic temperature effects on organ survival and restoration

PubMed Central

Ishikawa, Jun; Oshima, Masamitsu; Iwasaki, Fumitaka; Suzuki, Ryoji; Park, Joonhong; Nakao, Kazuhisa; Matsuzawa-Adachi, Yuki; Mizutsuki, Taro; Kobayashi, Ayaka; Abe, Yuta; Kobayashi, Eiji; Tezuka, Katsunari; Tsuji, Takashi

2015-01-01

A three-dimensional multicellular organism maintains the biological functions of life support by using the blood circulation to transport oxygen and nutrients and to regulate body temperature for intracellular enzymatic reactions. Donor organ transplantation using low-temperature storage is used as the fundamental treatment for dysfunctional organs. However, this approach has a serious problem in that donor organs maintain healthy conditions only during short-term storage. In this study, we developed a novel liver perfusion culture system based on biological metabolism that can maintain physiological functions, including albumin synthesis, bile secretion and urea production. This system also allows for the resurrection of a severely ischaemic liver. This study represents a significant advance for the development of an ex vivo organ perfusion system based on biological metabolism. It can be used not only to address donor organ shortages but also as the basis of future regenerative organ replacement therapy. PMID:25900715

Application of Nuclear Magnetic Resonance and Hybrid Methods to Structure Determination of Complex Systems.

PubMed

Prischi, Filippo; Pastore, Annalisa

2016-01-01

The current main challenge of Structural Biology is to undertake the structure determination of increasingly complex systems in the attempt to better understand their biological function. As systems become more challenging, however, there is an increasing demand for the parallel use of more than one independent technique to allow pushing the frontiers of structure determination and, at the same time, obtaining independent structural validation. The combination of different Structural Biology methods has been named hybrid approaches. The aim of this review is to critically discuss the most recent examples and new developments that have allowed structure determination or experimentally-based modelling of various molecular complexes selecting them among those that combine the use of nuclear magnetic resonance and small angle scattering techniques. We provide a selective but focused account of some of the most exciting recent approaches and discuss their possible further developments.

[Applications of synthetic biology in materials science].

PubMed

Zhao, Tianxin; Zhong, Chao

2017-03-25

Materials are the basis for human being survival and social development. To keep abreast with the increasing needs from all aspects of human society, there are huge needs in the development of advanced materials as well as high-efficiency but low-cost manufacturing strategies that are both sustainable and tunable. Synthetic biology, a new engineering principle taking gene regulation and engineering design as the core, greatly promotes the development of life sciences. This discipline has also contributed to the development of material sciences and will continuously bring new ideas to future new material design. In this paper, we review recent advances in applications of synthetic biology in material sciences, with the focus on how synthetic biology could enable synthesis of new polymeric biomaterials and inorganic materials, phage display and directed evolution of proteins relevant to materials development, living functional materials, engineered bacteria-regulated artificial photosynthesis system as well as applications of gene circuits for material sciences.

Materiomics: biological protein materials, from nano to macro.

PubMed

Cranford, Steven; Buehler, Markus J

2010-11-12

Materiomics is an emerging field of science that provides a basis for multiscale material system characterization, inspired in part by natural, for example, protein-based materials. Here we outline the scope and explain the motivation of the field of materiomics, as well as demonstrate the benefits of a materiomic approach in the understanding of biological and natural materials as well as in the design of de novo materials. We discuss recent studies that exemplify the impact of materiomics - discovering Nature's complexity through a materials science approach that merges concepts of material and structure throughout all scales and incorporates feedback loops that facilitate sensing and resulting structural changes at multiple scales. The development and application of materiomics is illustrated for the specific case of protein-based materials, which constitute the building blocks of a variety of biological systems such as tendon, bone, skin, spider silk, cells, and tissue, as well as natural composite material systems (a combination of protein-based and inorganic constituents) such as nacre and mollusk shells, and other natural multiscale systems such as cellulose-based plant and wood materials. An important trait of these materials is that they display distinctive hierarchical structures across multiple scales, where molecular details are exhibited in macroscale mechanical responses. Protein materials are intriguing examples of materials that balance multiple tasks, representing some of the most sustainable material solutions that integrate structure and function despite severe limitations in the quality and quantity of material building blocks. However, up until now, our attempts to analyze and replicate Nature's materials have been hindered by our lack of fundamental understanding of these materials' intricate hierarchical structures, scale-bridging mechanisms, and complex material components that bestow protein-based materials their unique properties. Recent advances in analytical tools and experimental methods allow a holistic view of such a hierarchical biological material system. The integration of these approaches and amalgamation of material properties at all scale levels to develop a complete description of a material system falls within the emerging field of materiomics. Materiomics is the result of the convergence of engineering and materials science with experimental and computational biology in the context of natural and synthetic materials. Through materiomics, fundamental advances in our understanding of structure-property-process relations of biological systems contribute to the mechanistic understanding of certain diseases and facilitate the development of novel biological, biologically inspired, and completely synthetic materials for applications in medicine (biomaterials), nanotechnology, and engineering.

Materiomics: biological protein materials, from nano to macro

PubMed Central

Cranford, Steven; Buehler, Markus J

2010-01-01

Materiomics is an emerging field of science that provides a basis for multiscale material system characterization, inspired in part by natural, for example, protein-based materials. Here we outline the scope and explain the motivation of the field of materiomics, as well as demonstrate the benefits of a materiomic approach in the understanding of biological and natural materials as well as in the design of de novo materials. We discuss recent studies that exemplify the impact of materiomics – discovering Nature’s complexity through a materials science approach that merges concepts of material and structure throughout all scales and incorporates feedback loops that facilitate sensing and resulting structural changes at multiple scales. The development and application of materiomics is illustrated for the specific case of protein-based materials, which constitute the building blocks of a variety of biological systems such as tendon, bone, skin, spider silk, cells, and tissue, as well as natural composite material systems (a combination of protein-based and inorganic constituents) such as nacre and mollusk shells, and other natural multiscale systems such as cellulose-based plant and wood materials. An important trait of these materials is that they display distinctive hierarchical structures across multiple scales, where molecular details are exhibited in macroscale mechanical responses. Protein materials are intriguing examples of materials that balance multiple tasks, representing some of the most sustainable material solutions that integrate structure and function despite severe limitations in the quality and quantity of material building blocks. However, up until now, our attempts to analyze and replicate Nature’s materials have been hindered by our lack of fundamental understanding of these materials’ intricate hierarchical structures, scale-bridging mechanisms, and complex material components that bestow protein-based materials their unique properties. Recent advances in analytical tools and experimental methods allow a holistic view of such a hierarchical biological material system. The integration of these approaches and amalgamation of material properties at all scale levels to develop a complete description of a material system falls within the emerging field of materiomics. Materiomics is the result of the convergence of engineering and materials science with experimental and computational biology in the context of natural and synthetic materials. Through materiomics, fundamental advances in our understanding of structure–property–process relations of biological systems contribute to the mechanistic understanding of certain diseases and facilitate the development of novel biological, biologically inspired, and completely synthetic materials for applications in medicine (biomaterials), nanotechnology, and engineering. PMID:24198478

ON THE MAKING OF A SYSTEM THEORY OF LIFE: PAUL A WEISS AND LUDWIG VON BERTALANFFY’S CONCEPTUAL CONNECTION

PubMed Central

Drack, Manfred; Apfalter, Wilfried; Pouvreau, David

2010-01-01

In this article, we review how two eminent Viennese system thinkers, Paul A Weiss and Ludwig von Bertalanffy, began to develop their own perspectives toward a system theory of life in the 1920s. Their work is especially rooted in experimental biology as performed at the Biologische Versuchsanstalt, as well as in philosophy, and they converge in basic concepts. We underline the conceptual connections of their thinking, among them the organism as an organized system, hierarchical organization, and primary activity. With their system thinking, both biologists shared a strong desire to overcome what they viewed as a “mechanistic” approach in biology. Their interpretations are relevant to the renaissance of system thinking in biology—“systems biology.” Unless otherwise noted, all translations are our own. PMID:18217527

Information theory in systems biology. Part II: protein-protein interaction and signaling networks.

PubMed

Mousavian, Zaynab; Díaz, José; Masoudi-Nejad, Ali

2016-03-01

By the development of information theory in 1948 by Claude Shannon to address the problems in the field of data storage and data communication over (noisy) communication channel, it has been successfully applied in many other research areas such as bioinformatics and systems biology. In this manuscript, we attempt to review some of the existing literatures in systems biology, which are using the information theory measures in their calculations. As we have reviewed most of the existing information-theoretic methods in gene regulatory and metabolic networks in the first part of the review, so in the second part of our study, the application of information theory in other types of biological networks including protein-protein interaction and signaling networks will be surveyed. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Compact "Water Window" Microscope with 60 nm Spatial Resolution for Applications in Biology and Nanotechnology.

PubMed

Wachulak, Przemyslaw; Torrisi, Alfio; Nawaz, Muhammad F; Bartnik, Andrzej; Adjei, Daniel; Vondrová, Šárka; Turňová, Jana; Jančarek, Alexandr; Limpouch, Jiří; Vrbová, Miroslava; Fiedorowicz, Henryk

2015-10-01

Short illumination wavelength allows an extension of the diffraction limit toward nanometer scale; thus, improving spatial resolution in optical systems. Soft X-ray (SXR) radiation, from "water window" spectral range, λ=2.3-4.4 nm wavelength, which is particularly suitable for biological imaging due to natural optical contrast provides better spatial resolution than one obtained with visible light microscopes. The high contrast in the "water window" is obtained because of selective radiation absorption by carbon and water, which are constituents of the biological samples. The development of SXR microscopes permits the visualization of features on the nanometer scale, but often with a tradeoff, which can be seen between the exposure time and the size and complexity of the microscopes. Thus, herein, we present a desk-top system, which overcomes the already mentioned limitations and is capable of resolving 60 nm features with very short exposure time. Even though the system is in its initial stage of development, we present different applications of the system for biology and nanotechnology. Construction of the microscope with recently acquired images of various samples will be presented and discussed. Such a high resolution imaging system represents an interesting solution for biomedical, material science, and nanotechnology applications.

Empirical modeling for intelligent, real-time manufacture control

NASA Technical Reports Server (NTRS)

Xu, Xiaoshu

1994-01-01

Artificial neural systems (ANS), also known as neural networks, are an attempt to develop computer systems that emulate the neural reasoning behavior of biological neural systems (e.g. the human brain). As such, they are loosely based on biological neural networks. The ANS consists of a series of nodes (neurons) and weighted connections (axons) that, when presented with a specific input pattern, can associate specific output patterns. It is essentially a highly complex, nonlinear, mathematical relationship or transform. These constructs have two significant properties that have proven useful to the authors in signal processing and process modeling: noise tolerance and complex pattern recognition. Specifically, the authors have developed a new network learning algorithm that has resulted in the successful application of ANS's to high speed signal processing and to developing models of highly complex processes. Two of the applications, the Weld Bead Geometry Control System and the Welding Penetration Monitoring System, are discussed in the body of this paper.

Modeling and simulation of high dimensional stochastic multiscale PDE systems at the exascale

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zabaras, Nicolas J.

2016-11-08

Predictive Modeling of multiscale and Multiphysics systems requires accurate data driven characterization of the input uncertainties, and understanding of how they propagate across scales and alter the final solution. This project develops a rigorous mathematical framework and scalable uncertainty quantification algorithms to efficiently construct realistic low dimensional input models, and surrogate low complexity systems for the analysis, design, and control of physical systems represented by multiscale stochastic PDEs. The work can be applied to many areas including physical and biological processes, from climate modeling to systems biology.

Biosynthetic inorganic chemistry.

PubMed

Lu, Yi

2006-08-25

Inorganic chemistry and biology can benefit greatly from each other. Although synthetic and physical inorganic chemistry have been greatly successful in clarifying the role of metal ions in biological systems, the time may now be right to utilize biological systems to advance coordination chemistry. One such example is the use of small, stable, easy-to-make, and well-characterized proteins as ligands to synthesize novel inorganic compounds. This biosynthetic inorganic chemistry is possible thanks to a number of developments in biology. This review summarizes the progress in the synthesis of close models of complex metalloproteins, followed by a description of recent advances in using the approach for making novel compounds that are unprecedented in either inorganic chemistry or biology. The focus is mainly on synthetic "tricks" learned from biology, as well as novel structures and insights obtained. The advantages and disadvantages of this biosynthetic approach are discussed.

3D molecular models of whole HIV-1 virions generated with cellPACK

PubMed Central

Goodsell, David S.; Autin, Ludovic; Forli, Stefano; Sanner, Michel F.; Olson, Arthur J.

2014-01-01

As knowledge of individual biological processes grows, it becomes increasingly useful to frame new findings within their larger biological contexts in order to generate new systems-scale hypotheses. This report highlights two major iterations of a whole virus model of HIV-1, generated with the cellPACK software. cellPACK integrates structural and systems biology data with packing algorithms to assemble comprehensive 3D models of cell-scale structures in molecular detail. This report describes the biological data, modeling parameters and cellPACK methods used to specify and construct editable models for HIV-1. Anticipating that cellPACK interfaces under development will enable researchers from diverse backgrounds to critique and improve the biological models, we discuss how cellPACK can be used as a framework to unify different types of data across all scales of biology. PMID:25253262

Bioinformatics for transporter pharmacogenomics and systems biology: data integration and modeling with UML.

PubMed

Yan, Qing

2010-01-01

Bioinformatics is the rational study at an abstract level that can influence the way we understand biomedical facts and the way we apply the biomedical knowledge. Bioinformatics is facing challenges in helping with finding the relationships between genetic structures and functions, analyzing genotype-phenotype associations, and understanding gene-environment interactions at the systems level. One of the most important issues in bioinformatics is data integration. The data integration methods introduced here can be used to organize and integrate both public and in-house data. With the volume of data and the high complexity, computational decision support is essential for integrative transporter studies in pharmacogenomics, nutrigenomics, epigenetics, and systems biology. For the development of such a decision support system, object-oriented (OO) models can be constructed using the Unified Modeling Language (UML). A methodology is developed to build biomedical models at different system levels and construct corresponding UML diagrams, including use case diagrams, class diagrams, and sequence diagrams. By OO modeling using UML, the problems of transporter pharmacogenomics and systems biology can be approached from different angles with a more complete view, which may greatly enhance the efforts in effective drug discovery and development. Bioinformatics resources of membrane transporters and general bioinformatics databases and tools that are frequently used in transporter studies are also collected here. An informatics decision support system based on the models presented here is available at http://www.pharmtao.com/transporter . The methodology developed here can also be used for other biomedical fields.

NEURODEVELOPMENTAL BIOLOGY ASSOCIATED WITH CHILDHOOD SEXUAL ABUSE

PubMed Central

De Bellis, Michael D.; Spratt, Eve G.; Hooper, Stephen R.

2013-01-01

Child maltreatment appears to be the single most preventable cause of mental illness and behavioral dysfunction in the US. There are few published studies examining the developmental and the psychobiological consequences of sexual abuse. There are multiple mechanisms through which sexual abuse can cause PTSD, activate biological stress response systems, and contribute to adverse brain development. This article will critically review the psychiatric problems associated with maltreatment and the emerging biologic stress system research with a special emphasis on what is known about victimization by sexual abuse. PMID:21970646

The pedestrian watchmaker: Genetic clocks from engineered oscillators

PubMed Central

Cookson, Natalie A.; Tsimring, Lev S.; Hasty, Jeff

2010-01-01

The crucial role of time-keeping has required organisms to develop sophisticated regulatory networks to ensure the reliable propagation of periodic behavior. These biological clocks have long been a focus of research; however, a clear understanding of how they maintain oscillations in the face of unpredictable environments and the inherent noise of biological systems remains elusive. Here, we review the current understanding of circadian oscillations using Drosophila melanogaster as a typical example and discuss the utility of an alternative synthetic biology approach to studying these highly intricate systems. PMID:19903483

Frontiers, Opportunities, and Challenges in Biochemical and Chemical Catalysis of CO2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Appel, Aaron M.; Bercaw, John E.; Bocarsly, Andrew B.

2013-08-14

Our central premise is that catalytic scientists can learn by studying how these important metabolic processes occur in nature. Complementarily, biochemists can learn by studying how catalytic scientists view these same chemical transformations promoted by synthetic catalysts. From these studies, hypotheses can be developed and tested through manipulation of enzyme structure and by synthesizing simple molecular catalysts to incorporate different structural features of the enzymes. It is hoped that these studies will lead to new and useful concepts in catalyst design for fuel production and utilization. This paper describes the results of a workshop held to explore these concepts inmore » regard to the development of new and more efficient catalytic processes for the conversion of CO2 to a variety of carbon-based fuels. The organization of this overview/review is as follows: 1) The first section briefly explores how interactions between the catalysis and biological communities have been fruitful in developing new catalysts for the reduction of protons to hydrogen, the simplest fuel generation reaction. 2) The second section assesses the state of the art in both biological and chemical reduction of CO2 by two electrons to form either carbon monoxide (CO) or formate (HCOO-). It also attempts to identify common principles between biological and synthetic catalysts and productive areas for future research. 3) The third section explores both biological and chemical processes that result in the reduction of CO2 beyond the level of CO and formate, again seeking to identify common principles and productive areas of future research. 4) The fourth section explores the formation of carbon-carbon bonds in biological and chemical systems in the same vein as the other sections. 5) A fifth section addresses the role of non-redox reactions of CO2 in biological systems and their role in carbon metabolism, with a parallel discussion of chemical systems. 6) In section 6, the topics of electrode modification, photochemical systems, and tandem catalysis are briefly discussed. These areas may be important for developing practical systems for CO2 reduction, and they share the common theme of coupling chemical reactions. 7) Section 7 describes some of the crosscutting activities that are critical for advancing the science underpinning catalyst development. 8) The last section attempts to summarize common issues in biological and chemical catalysis and to identify challenges that must be addressed to achieve practical catalysts that are suitable for the reduction of CO2 to fuels.« less

Research Frontiers in Bioinspired Energy: Molecular-Level Learning from Natural Systems: A Workshop

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zolandz, Dorothy

An interactive, multidisciplinary, public workshop, organized by a group of experts in biochemistry, biophysics, chemical and biomolecular engineering, chemistry, microbial metabolism, and protein structure and function, was held on January 6-7, 2011 in Washington, DC. Fundamental insights into the biological energy capture, storage, and transformation processes provided by speakers was featured in this workshop which included topics such as microbes living in extreme environments such as hydrothermal vents or caustic soda lakes (extremophiles) provided a fascinating basis for discussing the exploration and development of new energy systems. Breakout sessions and extended discussions among the multidisciplinary groups of participants in themore » workshop fostered information sharing and possible collaborations on future bioinspired research. Printed and web-based materials that summarize the committee's assessment of what transpired at the workshop were prepared to advance further understanding of fundamental chemical properties of biological systems within and between the disciplines. In addition, webbased materials (including two animated videos) were developed to make the workshop content more accessible to a broad audience of students and researchers working across disciplinary boundaries. Key workshop discussion topics included: Exploring and identifying novel organisms; Identifying patterns and conserved biological structures in nature; Exploring and identifying fundamental properties and mechanisms of known biological systems; Supporting current, and creating new, opportunities for interdisciplinary education, training, and outreach; and Applying knowledge from biology to create new devices and sustainable technology.« less

An algorithmic and information-theoretic approach to multimetric index construction

USGS Publications Warehouse

Schoolmaster, Donald R.; Grace, James B.; Schweiger, E. William; Guntenspergen, Glenn R.; Mitchell, Brian R.; Miller, Kathryn M.; Little, Amanda M.

2013-01-01

The use of multimetric indices (MMIs), such as the widely used index of biological integrity (IBI), to measure, track, summarize and infer the overall impact of human disturbance on biological communities has been steadily growing in recent years. Initially, MMIs were developed for aquatic communities using pre-selected biological metrics as indicators of system integrity. As interest in these bioassessment tools has grown, so have the types of biological systems to which they are applied. For many ecosystem types the appropriate biological metrics to use as measures of biological integrity are not known a priori. As a result, a variety of ad hoc protocols for selecting metrics empirically has developed. However, the assumptions made by proposed protocols have not be explicitly described or justified, causing many investigators to call for a clear, repeatable methodology for developing empirically derived metrics and indices that can be applied to any biological system. An issue of particular importance that has not been sufficiently addressed is the way that individual metrics combine to produce an MMI that is a sensitive composite indicator of human disturbance. In this paper, we present and demonstrate an algorithm for constructing MMIs given a set of candidate metrics and a measure of human disturbance. The algorithm uses each metric to inform a candidate MMI, and then uses information-theoretic principles to select MMIs that capture the information in the multidimensional system response from among possible MMIs. Such an approach can be used to create purely empirical (data-based) MMIs or can, optionally, be influenced by expert opinion or biological theory through the use of a weighting vector to create value-weighted MMIs. We demonstrate the algorithm with simulated data to demonstrate the predictive capacity of the final MMIs and with real data from wetlands from Acadia and Rocky Mountain National Parks. For the Acadia wetland data, the algorithm identified 4 metrics that combined to produce a -0.88 correlation with the human disturbance index. When compared to other methods, we find this algorithmic approach resulted in MMIs that were more predictive and comprise fewer metrics.

The Protein Information Management System (PiMS): a generic tool for any structural biology research laboratory

PubMed Central

Morris, Chris; Pajon, Anne; Griffiths, Susanne L.; Daniel, Ed; Savitsky, Marc; Lin, Bill; Diprose, Jonathan M.; Wilter da Silva, Alan; Pilicheva, Katya; Troshin, Peter; van Niekerk, Johannes; Isaacs, Neil; Naismith, James; Nave, Colin; Blake, Richard; Wilson, Keith S.; Stuart, David I.; Henrick, Kim; Esnouf, Robert M.

2011-01-01

The techniques used in protein production and structural biology have been developing rapidly, but techniques for recording the laboratory information produced have not kept pace. One approach is the development of laboratory information-management systems (LIMS), which typically use a relational database schema to model and store results from a laboratory workflow. The underlying philosophy and implementation of the Protein Information Management System (PiMS), a LIMS development specifically targeted at the flexible and unpredictable workflows of protein-production research laboratories of all scales, is described. PiMS is a web-based Java application that uses either Postgres or Oracle as the underlying relational database-management system. PiMS is available under a free licence to all academic laboratories either for local installation or for use as a managed service. PMID:21460443

The Protein Information Management System (PiMS): a generic tool for any structural biology research laboratory.

PubMed

Morris, Chris; Pajon, Anne; Griffiths, Susanne L; Daniel, Ed; Savitsky, Marc; Lin, Bill; Diprose, Jonathan M; da Silva, Alan Wilter; Pilicheva, Katya; Troshin, Peter; van Niekerk, Johannes; Isaacs, Neil; Naismith, James; Nave, Colin; Blake, Richard; Wilson, Keith S; Stuart, David I; Henrick, Kim; Esnouf, Robert M

2011-04-01

The techniques used in protein production and structural biology have been developing rapidly, but techniques for recording the laboratory information produced have not kept pace. One approach is the development of laboratory information-management systems (LIMS), which typically use a relational database schema to model and store results from a laboratory workflow. The underlying philosophy and implementation of the Protein Information Management System (PiMS), a LIMS development specifically targeted at the flexible and unpredictable workflows of protein-production research laboratories of all scales, is described. PiMS is a web-based Java application that uses either Postgres or Oracle as the underlying relational database-management system. PiMS is available under a free licence to all academic laboratories either for local installation or for use as a managed service.

The genome of herpesvirus papio 2 is closely related to the genomes of human herpes simplex viruses.

PubMed

Bigger, John E; Martin, David W

2003-06-01

Infection of baboons (Papio species) with herpesvirus papio 2 (HVP-2) produces a disease that is clinically similar to herpes simplex virus (HSV-1 and HSV-2) infection of humans. The development of a primate model of simplexvirus infection based on HVP-2 would provide a powerful resource to study virus biology and test vaccine strategies. In order to characterize the molecular biology of HVP-2 and justify further development of this model system we have constructed a physical map of the HVP-2 genome. The results of these studies have identified the presence of 26 reading frames that closely resemble HSV homologues. Furthermore, the HVP-2 genome shares a collinear arrangement with the genome of HSV. These studies further validate the development of the HVP-2 model as a surrogate system to study the biology of HSV infections.

Generation of the Dimensional Embryology Application (App) for Visualization of Early Chick and Frog Embryonic Development

ERIC Educational Resources Information Center

Webb, Rebecca L.; Bilitski, James; Zerbee, Alyssa; Symans, Alexandra; Chop, Alexandra; Seitz, Brianne; Tran, Cindy

2015-01-01

The study of embryonic development of multiple organisms, including model organisms such as frogs and chicks, is included in many undergraduate biology programs, as well as in a variety of graduate programs. As our knowledge of biological systems increases and the amount of material to be taught expands, the time spent instructing students about…

Dynamics of problem setting and framing in citizen discussions on synthetic biology.

PubMed

Betten, Afke Wieke; Broerse, Jacqueline E W; Kupper, Frank

2018-04-01

Synthetic biology is an emerging scientific field where engineers and biologists design and build biological systems for various applications. Developing synthetic biology responsibly in the public interest necessitates a meaningful societal dialogue. In this article, we argue that facilitating such a dialogue requires an understanding of how people make sense of synthetic biology. We performed qualitative research to unravel the underlying dynamics of problem setting and framing in citizen discussions on synthetic biology. We found that most people are not inherently for or against synthetic biology as a technology or development in itself, but that their perspectives are framed by core values about our relationships with science and technology and that sensemaking is much dependent on the context and general feelings of (dis)content. Given that there are many assumptions focused on a more binary idea of the public's view, we emphasize the need for frame awareness and understanding in a meaningful dialogue.

APDS: Autonomous Pathogen Detection System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Langlois, R G; Brown, S; Burris, L

An early warning system to counter bioterrorism, the Autonomous Pathogen Detection System (APDS) continuously monitors the environment for the presence of biological pathogens (e.g., anthrax) and once detected, it sounds an alarm much like a smoke detector warns of a fire. Long before September 11, 2001, this system was being developed to protect domestic venues and events including performing arts centers, mass transit systems, major sporting and entertainment events, and other high profile situations in which the public is at risk of becoming a target of bioterrorist attacks. Customizing off-the-shelf components and developing new components, a multidisciplinary team developed APDS,more » a stand-alone system for rapid, continuous monitoring of multiple airborne biological threat agents in the environment. The completely automated APDS samples the air, prepares fluid samples in-line, and performs two orthogonal tests: immunoassay and nucleic acid detection. When compared to competing technologies, APDS is unprecedented in terms of flexibility and system performance.« less

Synthetic biology platform technologies for antimicrobial applications.

PubMed

Braff, Dana; Shis, David; Collins, James J

2016-10-01

The growing prevalence of antibiotic resistance calls for new approaches in the development of antimicrobial therapeutics. Likewise, improved diagnostic measures are essential in guiding the application of targeted therapies and preventing the evolution of therapeutic resistance. Discovery platforms are also needed to form new treatment strategies and identify novel antimicrobial agents. By applying engineering principles to molecular biology, synthetic biologists have developed platforms that improve upon, supplement, and will perhaps supplant traditional broad-spectrum antibiotics. Efforts in engineering bacteriophages and synthetic probiotics demonstrate targeted antimicrobial approaches that can be fine-tuned using synthetic biology-derived principles. Further, the development of paper-based, cell-free expression systems holds promise in promoting the clinical translation of molecular biology tools for diagnostic purposes. In this review, we highlight emerging synthetic biology platform technologies that are geared toward the generation of new antimicrobial therapies, diagnostics, and discovery channels. Copyright © 2016 Elsevier B.V. All rights reserved.

Metabolic cancer biology: structural-based analysis of cancer as a metabolic disease, new sights and opportunities for disease treatment.

PubMed

Masoudi-Nejad, Ali; Asgari, Yazdan

2015-02-01

The cancer cell metabolism or the Warburg effect discovery goes back to 1924 when, for the first time Otto Warburg observed, in contrast to the normal cells, cancer cells have different metabolism. With the initiation of high throughput technologies and computational systems biology, cancer cell metabolism renaissances and many attempts were performed to revise the Warburg effect. The development of experimental and analytical tools which generate high-throughput biological data including lots of information could lead to application of computational models in biological discovery and clinical medicine especially for cancer. Due to the recent availability of tissue-specific reconstructed models, new opportunities in studying metabolic alteration in various kinds of cancers open up. Structural approaches at genome-scale levels seem to be suitable for developing diagnostic and prognostic molecular signatures, as well as in identifying new drug targets. In this review, we have considered these recent advances in structural-based analysis of cancer as a metabolic disease view. Two different structural approaches have been described here: topological and constraint-based methods. The ultimate goal of this type of systems analysis is not only the discovery of novel drug targets but also the development of new systems-based therapy strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Predictive Models of Nanotoxicity: Relationship of Physicochemical Properties to Particle Movement Through Biological Barriers

EPA Science Inventory

Understanding the linkage between the physicochemical (PC) properties of nanoparticles (NP) and their activation of biological systems is poorly understood, yet fundamental to predicting nanotoxicity, idenitifying mode of actions and developing appropriate and effective regul...

[Topical issues of biological safety under current conditions. Part 2. Conceptual, terminological, and definitive framework of biological safety].

PubMed

Onishchenko, G G; Smolenskiĭ, V Iu; Ezhlova, E B; Demina, Iu V; Toporkov, V P; Toporkov, A V; Liapin, M N; Kutyrev, V V

2013-01-01

In accordance with the established conceptual base for the up-to-date broad interpretation of biological safety, and IHR (2005), developed is the notional, terminological, and definitive framework, comprising 33 elements. Key item of the nomenclature is the biological safety that is identified as population safety (individual, social, national) from direct and (or) human environment mediated (occupational, socio-economic, geopolitical infrastructures, ecological system) exposures to hazardous biological factors. Ultimate objective of the biological safety provision is to prevent and liquidate aftermaths of emergency situations of biological character either of natural or human origin (anthropogenic) arising from direct and indirect impact of the biological threats to the public health compatible with national and international security hazard. Elaborated terminological framework allows for the construction of self-sufficient semantic content for biological safety provision, subject to formalization in legislative, normative and methodological respects and indicative of improvement as regards organizational and structural-functional groundwork of the Russian Federation National chemical and biological safety system, which is to become topical issue of Part 3.

An overview of bioinformatics methods for modeling biological pathways in yeast

PubMed Central

Hou, Jie; Acharya, Lipi; Zhu, Dongxiao

2016-01-01

The advent of high-throughput genomics techniques, along with the completion of genome sequencing projects, identification of protein–protein interactions and reconstruction of genome-scale pathways, has accelerated the development of systems biology research in the yeast organism Saccharomyces cerevisiae. In particular, discovery of biological pathways in yeast has become an important forefront in systems biology, which aims to understand the interactions among molecules within a cell leading to certain cellular processes in response to a specific environment. While the existing theoretical and experimental approaches enable the investigation of well-known pathways involved in metabolism, gene regulation and signal transduction, bioinformatics methods offer new insights into computational modeling of biological pathways. A wide range of computational approaches has been proposed in the past for reconstructing biological pathways from high-throughput datasets. Here we review selected bioinformatics approaches for modeling biological pathways in S. cerevisiae, including metabolic pathways, gene-regulatory pathways and signaling pathways. We start with reviewing the research on biological pathways followed by discussing key biological databases. In addition, several representative computational approaches for modeling biological pathways in yeast are discussed. PMID:26476430

Biocellion: accelerating computer simulation of multicellular biological system models.

PubMed

Kang, Seunghwa; Kahan, Simon; McDermott, Jason; Flann, Nicholas; Shmulevich, Ilya

2014-11-01

Biological system behaviors are often the outcome of complex interactions among a large number of cells and their biotic and abiotic environment. Computational biologists attempt to understand, predict and manipulate biological system behavior through mathematical modeling and computer simulation. Discrete agent-based modeling (in combination with high-resolution grids to model the extracellular environment) is a popular approach for building biological system models. However, the computational complexity of this approach forces computational biologists to resort to coarser resolution approaches to simulate large biological systems. High-performance parallel computers have the potential to address the computing challenge, but writing efficient software for parallel computers is difficult and time-consuming. We have developed Biocellion, a high-performance software framework, to solve this computing challenge using parallel computers. To support a wide range of multicellular biological system models, Biocellion asks users to provide their model specifics by filling the function body of pre-defined model routines. Using Biocellion, modelers without parallel computing expertise can efficiently exploit parallel computers with less effort than writing sequential programs from scratch. We simulate cell sorting, microbial patterning and a bacterial system in soil aggregate as case studies. Biocellion runs on x86 compatible systems with the 64 bit Linux operating system and is freely available for academic use. Visit http://biocellion.com for additional information. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Microfluidic Approaches to Synchrotron Radiation-Based Fourier Transform Infrared (SR-FTIR) Spectral Microscopy of Living Biosystems

PubMed Central

Loutherback, Kevin; Birarda, Giovanni; Chen, Liang; Holman, Hoi-Ying N.

2016-01-01

A long-standing desire in biological and biomedical sciences is to be able to probe cellular chemistry as biological processes are happening inside living cells. Synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectral microscopy is a label-free and nondestructive analytical technique that can provide spatiotemporal distributions and relative abundances of biomolecules of a specimen by their characteristic vibrational modes. Despite great progress in recent years, SR-FTIR imaging of living biological systems remains challenging because of the demanding requirements on environmental control and strong infrared absorption of water. To meet this challenge, microfluidic devices have emerged as a method to control the water thickness while providing a hospitable environment to measure cellular processes and responses over many hours or days. This paper will provide an overview of microfluidic device development for SR-FTIR imaging of living biological systems, provide contrast between the various techniques including closed and open-channel designs, and discuss future directions of development within this area. Even as the fundamental science and technological demonstrations develop, other ongoing issues must be addressed; for example, choosing applications whose experimental requirements closely match device capabilities, and developing strategies to efficiently complete the cycle of development. These will require imagination, ingenuity and collaboration. PMID:26732243

Microfluidic approaches to synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectral microscopy of living biosystems

DOE PAGES

Loutherback, Kevin; Birarda, Giovanni; Chen, Liang; ...

2016-02-15

A long-standing desire in biological and biomedical sciences is to be able to probe cellular chemistry as biological processes are happening inside living cells. Synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectral microscopy is a label-free and nondestructive analytical technique that can provide spatiotemporal distributions and relative abundances of biomolecules of a specimen by their characteristic vibrational modes. Despite great progress in recent years, SR-FTIR imaging of living biological systems remains challenging because of the demanding requirements on environmental control and strong infrared absorption of water. To meet this challenge, microfluidic devices have emerged as a method to control the watermore » thickness while providing a hospitable environment to measure cellular processes and responses over many hours or days. This paper will provide an overview of microfluidic device development for SR-FTIR imaging of living biological systems, provide contrast between the various techniques including closed and open-channel designs, and discuss future directions of development within this area. Even as the fundamental science and technological demonstrations develop, other ongoing issues must be addressed; for example, choosing applications whose experimental requirements closely match device capabilities, and developing strategies to efficiently complete the cycle of development. These will require imagination, ingenuity and collaboration.« less

Microfluidic approaches to synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectral microscopy of living biosystems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loutherback, Kevin; Birarda, Giovanni; Chen, Liang

A long-standing desire in biological and biomedical sciences is to be able to probe cellular chemistry as biological processes are happening inside living cells. Synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectral microscopy is a label-free and nondestructive analytical technique that can provide spatiotemporal distributions and relative abundances of biomolecules of a specimen by their characteristic vibrational modes. Despite great progress in recent years, SR-FTIR imaging of living biological systems remains challenging because of the demanding requirements on environmental control and strong infrared absorption of water. To meet this challenge, microfluidic devices have emerged as a method to control the watermore » thickness while providing a hospitable environment to measure cellular processes and responses over many hours or days. This paper will provide an overview of microfluidic device development for SR-FTIR imaging of living biological systems, provide contrast between the various techniques including closed and open-channel designs, and discuss future directions of development within this area. Even as the fundamental science and technological demonstrations develop, other ongoing issues must be addressed; for example, choosing applications whose experimental requirements closely match device capabilities, and developing strategies to efficiently complete the cycle of development. These will require imagination, ingenuity and collaboration.« less

Bioengineering Spin-Offs from Dynamical Systems Theory

NASA Astrophysics Data System (ADS)

Collins, J. J.

1997-03-01

Recently, there has been considerable interest in applying concepts and techniques from dynamical systems and statistical physics to physiological systems. In this talk, we present work dealing which two active topics in this area: stochastic resonance and (2) chaos control. Stochastic resonance is a phenomenon wherein the response of nonlinear system to a weak input signal is optimally enhanced by the presence of a particular level of noise. Here we demonstrate that noise-based techniques can be used to lower sensory detection thresholds in humans. We discuss how from a bioengineering and clinical standpoint, these developments may be particularly relevant for individuals with elevated sensory thresholds, such as older adults and patients with peripheral neuropathy. Chaos control techniques have been applied to a wide range of experimental systems, including biological preparations. The application of chaos control to biological systems has led to speculations that these methods may be clinically useful. Here we demonstrate that the principles of chaos control can be utilized to stabilize underlying unstable periodic orbits in non-chaotic biological systems. We discuss how from a bioengineering and clinical standpoint, these developments may be important for suppressing or eliminating certain types of cardiac arrhythmias.

Current status of biotechnology in Slovakia.

PubMed

Stuchlík, Stanislav; Turna, Ján

2013-07-01

The United Nations Convention on Biological Diversity defines biotechnology as: 'Any technological application that uses biological systems, living organisms, or derivatives thereof, to make or modify products or processes for specific use.' In other words biotechnology is 'application of scientific and technical advances in life science to develop commercial products' or briefly 'the use of molecular biology for useful purposes'. This short overview is about different branches of biotechnology carried out in Slovakia and it shows that Slovakia has a good potential for further development of modern biotechnologies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Computational Systems Biology in Cancer: Modeling Methods and Applications

PubMed Central

Materi, Wayne; Wishart, David S.

2007-01-01

In recent years it has become clear that carcinogenesis is a complex process, both at the molecular and cellular levels. Understanding the origins, growth and spread of cancer, therefore requires an integrated or system-wide approach. Computational systems biology is an emerging sub-discipline in systems biology that utilizes the wealth of data from genomic, proteomic and metabolomic studies to build computer simulations of intra and intercellular processes. Several useful descriptive and predictive models of the origin, growth and spread of cancers have been developed in an effort to better understand the disease and potential therapeutic approaches. In this review we describe and assess the practical and theoretical underpinnings of commonly-used modeling approaches, including ordinary and partial differential equations, petri nets, cellular automata, agent based models and hybrid systems. A number of computer-based formalisms have been implemented to improve the accessibility of the various approaches to researchers whose primary interest lies outside of model development. We discuss several of these and describe how they have led to novel insights into tumor genesis, growth, apoptosis, vascularization and therapy. PMID:19936081

Environmental Characterization of Mine Countermeasure Test Ranges: Hydrography and Water Column Optics

DTIC Science & Technology

2015-09-30

changes in near-shore water columns and support companion laser imaging system tests. The physical, biological and optical oceanographic data...developed under this project will be used as input to optical and environmental models to assess the performance characteristics of laser imaging systems...OBJECTIVES We proposed to characterize the physical, biological and optical fields present during deployments of the Streak Tube Imaging Lidar

Using parallel evolutionary development for a biologically-inspired computer vision system for mobile robots.

PubMed

Wright, Cameron H G; Barrett, Steven F; Pack, Daniel J

2005-01-01

We describe a new approach to attacking the problem of robust computer vision for mobile robots. The overall strategy is to mimic the biological evolution of animal vision systems. Our basic imaging sensor is based upon the eye of the common house fly, Musca domestica. The computational algorithms are a mix of traditional image processing, subspace techniques, and multilayer neural networks.

VirtualPlant: A Software Platform to Support Systems Biology Research1[W][OA

PubMed Central

Katari, Manpreet S.; Nowicki, Steve D.; Aceituno, Felipe F.; Nero, Damion; Kelfer, Jonathan; Thompson, Lee Parnell; Cabello, Juan M.; Davidson, Rebecca S.; Goldberg, Arthur P.; Shasha, Dennis E.; Coruzzi, Gloria M.; Gutiérrez, Rodrigo A.

2010-01-01

Data generation is no longer the limiting factor in advancing biological research. In addition, data integration, analysis, and interpretation have become key bottlenecks and challenges that biologists conducting genomic research face daily. To enable biologists to derive testable hypotheses from the increasing amount of genomic data, we have developed the VirtualPlant software platform. VirtualPlant enables scientists to visualize, integrate, and analyze genomic data from a systems biology perspective. VirtualPlant integrates genome-wide data concerning the known and predicted relationships among genes, proteins, and molecules, as well as genome-scale experimental measurements. VirtualPlant also provides visualization techniques that render multivariate information in visual formats that facilitate the extraction of biological concepts. Importantly, VirtualPlant helps biologists who are not trained in computer science to mine lists of genes, microarray experiments, and gene networks to address questions in plant biology, such as: What are the molecular mechanisms by which internal or external perturbations affect processes controlling growth and development? We illustrate the use of VirtualPlant with three case studies, ranging from querying a gene of interest to the identification of gene networks and regulatory hubs that control seed development. Whereas the VirtualPlant software was developed to mine Arabidopsis (Arabidopsis thaliana) genomic data, its data structures, algorithms, and visualization tools are designed in a species-independent way. VirtualPlant is freely available at www.virtualplant.org. PMID:20007449

Agent-Based Modeling in Molecular Systems Biology.

PubMed

Soheilypour, Mohammad; Mofrad, Mohammad R K

2018-07-01

Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease. © 2018 WILEY Periodicals, Inc.

[Chronobiology of immune system].

PubMed

Trufakin, V A; Shurlygina, A V; Dergacheva, T I; Litvinenko, G I; Verbitskaia, L V

1999-01-01

The biological rhythmological programme of the immune system is a constituent of the body's common biological rhythmological programme. Its pattern seems to be genetically determined and reflects the functional status of the system. The chronobiological mechanisms responsible for the regulation of immune functions lie in the presence of certain phasic interrelations between the biological rhythms of the synthesis and production of regulatory agents on the one hand, and those of the receptor system and metabolic potential of immunocompetent cells on the other. The facts given in the paper may be a basis for a chronobiological approach to better understanding the mechanisms of the physiology and pathology of the immune system. The medical significance of study of the structural and temporal pattern of the immune system consists in the development of new techniques for diagnosis, prognosis, therapy, and assessment of risk factors in immunopathological conditions.

Systems biology driven software design for the research enterprise

PubMed Central

Boyle, John; Cavnor, Christopher; Killcoyne, Sarah; Shmulevich, Ilya

2008-01-01

Background In systems biology, and many other areas of research, there is a need for the interoperability of tools and data sources that were not originally designed to be integrated. Due to the interdisciplinary nature of systems biology, and its association with high throughput experimental platforms, there is an additional need to continually integrate new technologies. As scientists work in isolated groups, integration with other groups is rarely a consideration when building the required software tools. Results We illustrate an approach, through the discussion of a purpose built software architecture, which allows disparate groups to reuse tools and access data sources in a common manner. The architecture allows for: the rapid development of distributed applications; interoperability, so it can be used by a wide variety of developers and computational biologists; development using standard tools, so that it is easy to maintain and does not require a large development effort; extensibility, so that new technologies and data types can be incorporated; and non intrusive development, insofar as researchers need not to adhere to a pre-existing object model. Conclusion By using a relatively simple integration strategy, based upon a common identity system and dynamically discovered interoperable services, a light-weight software architecture can become the focal point through which scientists can both get access to and analyse the plethora of experimentally derived data. PMID:18578887

Molecular Force Spectroscopy on Cells

NASA Astrophysics Data System (ADS)

Liu, Baoyu; Chen, Wei; Zhu, Cheng

2015-04-01

Molecular force spectroscopy has become a powerful tool to study how mechanics regulates biology, especially the mechanical regulation of molecular interactions and its impact on cellular functions. This force-driven methodology has uncovered a wealth of new information of the physical chemistry of molecular bonds for various biological systems. The new concepts, qualitative and quantitative measures describing bond behavior under force, and structural bases underlying these phenomena have substantially advanced our fundamental understanding of the inner workings of biological systems from the nanoscale (molecule) to the microscale (cell), elucidated basic molecular mechanisms of a wide range of important biological processes, and provided opportunities for engineering applications. Here, we review major force spectroscopic assays, conceptual developments of mechanically regulated kinetics of molecular interactions, and their biological relevance. We also present current challenges and highlight future directions.

CRISPR Editing in Biological and Biomedical Investigation.

PubMed

Ju, Xing-Da; Xu, Jing; Sun, Zhong Sheng

2018-01-01

The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR-associated protein) system, a prokaryotic RNA-based adaptive immune system against viral infection, is emerging as a powerful genome editing tool in broad research areas. To further improve and expand its functionality, various CRISPR delivery strategies have been tested and optimized, and key CRISPR system components such as Cas protein have been engineered with different purposes. Benefiting from more in-depth understanding and further development of CRISPR, versatile CRISPR-based platforms for genome editing have been rapidly developed to advance investigations in biology and biomedicine. In biological research area, CRISPR has been widely adopted in both fundamental and applied research fields, such as genomic and epigenomic modification, genome-wide screening, cell and animal research, agriculture transforming, livestock breeding, food manufacture, industrial biotechnology, and gene drives in disease agents control. In biomedical research area, CRISPR has also shown its extensive applicability in the establishment of animal models for genetic disorders, generation of tissue donors, implementation of antimicrobial and antiviral studies, identification and assessment of new drugs, and even treatment for clinical diseases. However, there are still several problems to consider, and the biggest concerns are the off-target effects and ethical issues of this technology. In this prospect article, after highlighting recent development of CRISPR systems, we outline different applications and current limitations of CRISPR in biological and biomedical investigation. Finally, we provide a perspective on future development and potential risks of this multifunctional technology. J. Cell. Biochem. 119: 52-61, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Quantum chemical methods for the investigation of photoinitiated processes in biological systems: theory and applications.

PubMed

Dreuw, Andreas

2006-11-13

With the advent of modern computers and advances in the development of efficient quantum chemical computer codes, the meaningful computation of large molecular systems at a quantum mechanical level became feasible. Recent experimental effort to understand photoinitiated processes in biological systems, for instance photosynthesis or vision, at a molecular level also triggered theoretical investigations in this field. In this Minireview, standard quantum chemical methods are presented that are applicable and recently used for the calculation of excited states of photoinitiated processes in biological molecular systems. These methods comprise configuration interaction singles, the complete active space self-consistent field method, and time-dependent density functional theory and its variants. Semiempirical approaches are also covered. Their basic theoretical concepts and mathematical equations are briefly outlined, and their properties and limitations are discussed. Recent successful applications of the methods to photoinitiated processes in biological systems are described and theoretical tools for the analysis of excited states are presented.

Multidisciplinary Russian biomedical research in space

NASA Astrophysics Data System (ADS)

Orlov, O. I.; Sychev, V. N.; Samarin, G. I.; Ilyin, E. A.; Belakovskiy, M. S.; Kussmaul, A. R.

2014-08-01

Research activities on a comprehensive multidisciplinary program are vital for enhancement of the system of crew's medical care, environmental health and hygiene in space missions. The primary goal of the program must be identification of patterns, intensity and dynamics of structural and functional shifts in organism induced by an aggregate of spaceflight factors including microgravity, isolation, artificial environment, space radiation, etc. Also, the program must pursue differential assessment of emerging deviations from the standpoint of adequacy to the spaceflight conditions and prospects of returning to Earth and guide the development of principles, methods and techniques necessary to maintain health and working capacity of humans during short- and long-duration missions and on return to Earth. Over 50 years, since 1963, the IBMP researchers apply systemic and innovational approaches to fundamental and exploratory studies in the fields of medical sciences, radiation biology, engineering science, biotechnology, etc. with participation of various biological specimens and human volunteers. Investigations aboard manned spacecrafts and biological satellites as well as in ground-based laboratories further enhancement of the medical care system for crews on orbital and remote space missions; they give insight into the fundamental problems of gravitational physiology and biology, psychophysiology, radiation biology, and contribute thereby to the development of knowledge, methods and technologies, as well as medical and scientific equipment.

[Topical issues of biological safety under current conditions. Part 3. Scientific provision for the national regulation of the biological safety framework in its broad interpretation].

PubMed

Onishchenko, G G; Smolensky, V Yu; Ezhlova, E B; Demina, Yu V; Toporkov, V P; Toporkov, A V; Lyapin, M N; Kutyrev, V V

2014-01-01

Consequent of investigation concerned with biological safety (BS) framework development in its broad interpretation, reflected in the Russian Federation State Acts, identified have been conceptual entity parameters of the up-to-date broad interpretation of BS, which have formed a part of the developed by the authors system for surveillance (prophylaxis, localization, indication, identification, and diagnostics) and control (prophylaxis, localization, and response/elimination) over the emergency situations of biological (sanitary-epidemiological) character. The System functionality is activated through supplying the content with information data which are concerned with monitoring and control of specific internal and external threats in the sphere of BS provision fixed in the Supplement 2 of the International Health Regulations (IHR, 2005), and with the previously characterized nomenclature of hazardous biological factors. The system is designed as a network-based research-and-practice tool for evaluation of the situation in the sphere of BS provision, as well as assessment of efficacy of management decision making as regards BS control and proper State policy implementation. Most of the system elements either directly or indirectly relate to the scope of activities conducted by Federal Service for Surveillance in the Sphere of Consumers Rights Protection and Human Welfare, being substantial argument for allocating coordination functions in the sphere of BS provision to this government agency and consistent with its function as the State Coordinator on IHR (2005). The data collected serve as materials to Draft Federal Law "Concerning biological safety provision of the population".

Emerging therapies in systemic lupus erythematous: from clinical trial to the real life.

PubMed

Zhang, Huza; Chambers, William; Sciascia, Savino; Cuadrado, Maria J

2016-01-01

Systemic lupus erythematous (SLE) is a chronic autoimmune disease characterised by multisystem involvement and a relapsing remitting course. SLE is a highly heterogeneous condition, with wide variations in both the presentation and severity of disease and the biological markers identified. The use of biologics in SLE has lagged behind that of other rheumatological conditions such as rheumatoid arthritis, in part due to the diverse clinical manifestations of SLE, making it difficult to design appropriate trials for novel treatments. As such, broad immunosuppressive treatment regimens are still widely used in SLE. Nevertheless, in recent years, elucidation of some aspects of SLE pathogenesis have allowed the development of therapies targeted at molecular mediators of SLE. This review provides an update of biological available therapies and those currently under development.

Constructive biology and approaches to temporal grounding in postreactive robotics

NASA Astrophysics Data System (ADS)

Nehaniv, Chrystopher L.; Dautenhahn, Kerstin; Loomes, Martin J.

1999-08-01

Constructive Biology means understanding biological mechanisms through building systems that exhibit life-like properties. Applications include learning engineering tricks from biological system, as well as the validation in biological modeling. In particular, biological system in the course of development and experience become temporally grounded. Researchers attempting to transcend mere reactivity have been inspired by the drives, motivations, homeostasis, hormonal control, and emotions of animals. In order to contextualize and modulate behavior, these ideas have been introduced into robotics and synthetic agents, while further flexibility is achieved by introducing learning. Broadening scope of the temporal horizon further requires post-reactive techniques that address not only the action in the now, although such action may perhaps be modulated by drives and affect. Support is needed for expressing and benefitting from pats experiences, predictions of the future, and form interaction histories of the self with the world and with other agents. Mathematical methods provide a new way to support such grounding in the construction of post-reactive systems. Moreover, the communication of such mathematical encoded histories of experience between situated agents opens a route to narrative intelligence, analogous to communication or story telling in societies.

Systems healthcare: a holistic paradigm for tomorrow.

PubMed

Fiandaca, Massimo S; Mapstone, Mark; Connors, Elenora; Jacobson, Mireille; Monuki, Edwin S; Malik, Shaista; Macciardi, Fabio; Federoff, Howard J

2017-12-19

Systems healthcare is a holistic approach to health premised on systems biology and medicine. The approach integrates data from molecules, cells, organs, the individual, families, communities, and the natural and man-made environment. Both extrinsic and intrinsic influences constantly challenge the biological networks associated with wellness. Such influences may dysregulate networks and allow pathobiology to evolve, resulting in early clinical presentation that requires astute assessment and timely intervention for successful mitigation. Herein, we describe the components of relevant biological systems and the nature of progression from at-risk to manifest disease. We illustrate the systems approach by examining two relevant clinical examples: Alzheimer's and cardiovascular diseases. The implications of systems healthcare management are examined through the lens of economics, ethics, policy and the law. Finally, we propose the need to develop new educational paradigms to enhance the training of the health professional in an era of systems medicine.

Developing and establishing bee species as crop pollinators: the example of Osmia spp. (Hymenoptera: Megachilidae) and fruit trees.

PubMed

Bosch, J; Bosch, J; Kemp, W P

2002-02-01

The development of a bee species as a new crop pollinator starts with the identification of a pollination-limited crop production deficit and the selection of one or more candidate pollinator species. The process continues with a series of studies on the developmental biology, pollinating efficacy, nesting behaviour, preference for different nesting substrates, and population dynamics of the candidate pollinator. Parallel studies investigate the biology of parasites, predators and pathogens. The information gained in these studies is combined with information on the reproductive biology of the crop to design a management system. Complete management systems should provide guidelines on rearing and releasing methods, bee densities required for adequate pollination, nesting materials, and control against parasites, predators and pathogens. Management systems should also provide methods to ensure a reliable pollinator supply. Pilot tests on a commercial scale are then conducted to test and eventually refine the management system. The process culminates with the delivery of a viable system to manage and sustain the new pollinator on a commercial scale. The process is illustrated by the development of three mason bees, Osmia cornifrons (Radoszkowski), O. lignaria Say and O. cornuta (Latreille) as orchard pollinators in Japan, the USA and Europe, respectively.

openBIS: a flexible framework for managing and analyzing complex data in biology research

PubMed Central

2011-01-01

Background Modern data generation techniques used in distributed systems biology research projects often create datasets of enormous size and diversity. We argue that in order to overcome the challenge of managing those large quantitative datasets and maximise the biological information extracted from them, a sound information system is required. Ease of integration with data analysis pipelines and other computational tools is a key requirement for it. Results We have developed openBIS, an open source software framework for constructing user-friendly, scalable and powerful information systems for data and metadata acquired in biological experiments. openBIS enables users to collect, integrate, share, publish data and to connect to data processing pipelines. This framework can be extended and has been customized for different data types acquired by a range of technologies. Conclusions openBIS is currently being used by several SystemsX.ch and EU projects applying mass spectrometric measurements of metabolites and proteins, High Content Screening, or Next Generation Sequencing technologies. The attributes that make it interesting to a large research community involved in systems biology projects include versatility, simplicity in deployment, scalability to very large data, flexibility to handle any biological data type and extensibility to the needs of any research domain. PMID:22151573

Synthetic Nanoelectronic Probes for Biological Cells and Tissue

PubMed Central

2013-01-01

Research at the interface between nanoscience and biology has the potential to produce breakthroughs in fundamental science and lead to revolutionary technologies. In this review, we focus on nanoelectronic/biological interfaces. First, we discuss nanoscale field effect transistors (nanoFETs) as probes to study cellular systems, including the realization of nanoFET comparable in size to biological nanostructures involved in communication using synthesized nanowires. Second, we overview current progress in multiplexed extracellular sensing using planar nanoFET arrays. Third, we describe the design and implementation of three distinct nanoFETs used to realize the first intracellular electrical recording from single cells. Fourth, we present recent progress in merging electronic and biological systems at the 3D tissue level by using macroporous nanoelectronic scaffolds. Finally, we discuss future development in this research area, the unique challenges and opportunities, and the tremendous impact these nanoFET based technologies might have in advancing biology and medical sciences. PMID:23451719

AN EPA SPONSORED LITERATURE REVIEW DATABASE TO SUPPORT STRESSOR IDENTIFICATION

EPA Science Inventory

The Causal Analysis/Diagnosis Decision Information System (CADDIS) is an EPA decision-support system currently under development for evaluating the biological impact of stressors on water bodies. In support of CADDIS, EPA is developing CADLIT, a searchable database of the scient...

Enhanced sampling techniques in molecular dynamics simulations of biological systems.

PubMed

Bernardi, Rafael C; Melo, Marcelo C R; Schulten, Klaus

2015-05-01

Molecular dynamics has emerged as an important research methodology covering systems to the level of millions of atoms. However, insufficient sampling often limits its application. The limitation is due to rough energy landscapes, with many local minima separated by high-energy barriers, which govern the biomolecular motion. In the past few decades methods have been developed that address the sampling problem, such as replica-exchange molecular dynamics, metadynamics and simulated annealing. Here we present an overview over theses sampling methods in an attempt to shed light on which should be selected depending on the type of system property studied. Enhanced sampling methods have been employed for a broad range of biological systems and the choice of a suitable method is connected to biological and physical characteristics of the system, in particular system size. While metadynamics and replica-exchange molecular dynamics are the most adopted sampling methods to study biomolecular dynamics, simulated annealing is well suited to characterize very flexible systems. The use of annealing methods for a long time was restricted to simulation of small proteins; however, a variant of the method, generalized simulated annealing, can be employed at a relatively low computational cost to large macromolecular complexes. Molecular dynamics trajectories frequently do not reach all relevant conformational substates, for example those connected with biological function, a problem that can be addressed by employing enhanced sampling algorithms. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014 Elsevier B.V. All rights reserved.

Information security management system planning for CBRN facilities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lenaeu, Joseph D.; O'Neil, Lori Ross; Leitch, Rosalyn M.

The focus of this document is to provide guidance for the development of information security management system planning documents at chemical, biological, radiological, or nuclear (CBRN) facilities. It describes a risk-based approach for planning information security programs based on the sensitivity of the data developed, processed, communicated, and stored on facility information systems.

Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? What Really Constitutes the Study of "Systems Biology" and How Might Such an Approach Facilitate Vaccine Design.

PubMed

Germain, Ronald N

2017-10-16

A dichotomy exists in the field of vaccinology about the promise versus the hype associated with application of "systems biology" approaches to rational vaccine design. Some feel it is the only way to efficiently uncover currently unknown parameters controlling desired immune responses or discover what elements actually mediate these responses. Others feel that traditional experimental, often reductionist, methods for incrementally unraveling complex biology provide a more solid way forward, and that "systems" approaches are costly ways to collect data without gaining true insight. Here I argue that both views are inaccurate. This is largely because of confusion about what can be gained from classical experimentation versus statistical analysis of large data sets (bioinformatics) versus methods that quantitatively explain emergent properties of complex assemblies of biological components, with the latter reflecting what was previously called "physiology." Reductionist studies will remain essential for generating detailed insight into the functional attributes of specific elements of biological systems, but such analyses lack the power to provide a quantitative and predictive understanding of global system behavior. But by employing (1) large-scale screening methods for discovery of unknown components and connections in the immune system ( omics ), (2) statistical analysis of large data sets ( bioinformatics ), and (3) the capacity of quantitative computational methods to translate these individual components and connections into models of emergent behavior ( systems biology ), we will be able to better understand how the overall immune system functions and to determine with greater precision how to manipulate it to produce desired protective responses. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Circadian System, Sleep and Endocrinology

PubMed Central

Morris, Christopher J.; Aeschbach, Daniel; Scheer, Frank A.J.L.

2011-01-01

Levels of numerous hormones vary across the day and night. Such fluctuations are not only attributable to changes in sleep/wakefulness and other behaviors but also to a biological timing system governed by the suprachiasmatic nucleus of the hypothalamus. Sleep has a strong effect on levels of some hormones such as growth hormone but little effect on others which are more strongly regulated by the biological timing system (e.g., melatonin). Whereas the exact mechanisms through which sleep affects circulating hormonal levels are poorly understood, more is known about how the biological timing system influences the secretion of hormones. The suprachiasmatic nucleus exerts its influence on hormones via neuronal and humoral signals but it is also now apparent that peripheral cells can rhythmically secrete hormones independent of signals from the suprachiasmatic nucleus. Under normal circumstances, behaviors and the biological timing system are synchronized and consequently hormonal systems are exquisitely regulated. However, many individuals (e.g., shift-workers) frequently undergo circadian misalignment by desynchronizing their sleep/wake cycle from the biological timing system. Recent experiments indicate that circadian misalignment has an adverse effect on metabolic and hormonal factors such as glucose and insulin. Further research is needed to determine the underlying mechanisms that cause the negative effects induced by circadian misalignment. Such research could aid the development of countermeasures for circadian misalignment. PMID:21939733

Clustering of 3D-Structure Similarity Based Network of Secondary Metabolites Reveals Their Relationships with Biological Activities.

PubMed

Ohtana, Yuki; Abdullah, Azian Azamimi; Altaf-Ul-Amin, Md; Huang, Ming; Ono, Naoaki; Sato, Tetsuo; Sugiura, Tadao; Horai, Hisayuki; Nakamura, Yukiko; Morita Hirai, Aki; Lange, Klaus W; Kibinge, Nelson K; Katsuragi, Tetsuo; Shirai, Tsuyoshi; Kanaya, Shigehiko

2014-12-01

Developing database systems connecting diverse species based on omics is the most important theme in big data biology. To attain this purpose, we have developed KNApSAcK Family Databases, which are utilized in a number of researches in metabolomics. In the present study, we have developed a network-based approach to analyze relationships between 3D structure and biological activity of metabolites consisting of four steps as follows: construction of a network of metabolites based on structural similarity (Step 1), classification of metabolites into structure groups (Step 2), assessment of statistically significant relations between structure groups and biological activities (Step 3), and 2-dimensional clustering of the constructed data matrix based on statistically significant relations between structure groups and biological activities (Step 4). Applying this method to a data set consisting of 2072 secondary metabolites and 140 biological activities reported in KNApSAcK Metabolite Activity DB, we obtained 983 statistically significant structure group-biological activity pairs. As a whole, we systematically analyzed the relationship between 3D-chemical structures of metabolites and biological activities. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fort Ord’s Merit-Reward System: A Contingency Management Program in Basic Combat Training,

DTIC Science & Technology

1979-01-01

medicine colleague, Dr. Llewellyn Legters , that the recommendation emerged to develop and test a contingency management system for basic training. One...1965, 16, 438. 9Datel, W. E., & Legters , L. J. Reinforcement measurement in a social system. Journal of Biological Psychology, 1971, 13 (1), 33-38 13...ODatel, W. E., & Legters , L. J. The psychology of the Army recruit. Journal of Biological Psychology, 1970-71, 12, 34-40. l1Datel, W. E. Technical

System Theory and Physiological Processes.

PubMed

Jones, R W

1963-05-03

Engineers and physiologists working together in experimental and theoretical studies predict that the application of system analysis to biological processes will increase understanding of these processes and broaden the base of system theory. Richard W. Jones, professor of electrical engineering at Northwestern University, Evanston, Illinois, and John S. Gray, professor of physiology at Northwestern's Medical School, discuss these developments. Their articles are adapted from addresses delivered in Chicago in November 1962 at the 15th Annual Conference on Engineering in Medicine and Biology.

Deriving principles of microbiology by multiscaling laws of molecular physics.

PubMed

Ortoleva, Peter; Adhangale, P; Cheluvaraja, S; Fontus, Max; Shreif, Zeina

2009-01-01

It has long been an objective of the physical sciences to derive principles of biology from the laws of physics. At the angstrom scale for processes evolving on timescales of 10(-14) s, many systems can be characterized in terms of atomic vibrations and collisions. In contrast, biological systems display dramatic transformations including self-assembly and reorganization from one cell phenotype to another as the microenvironment changes. We have developed a framework for understanding the emergence of living systems from the underlying atomic chaos.

EDITORIAL: Physical Biology

NASA Astrophysics Data System (ADS)

Roscoe, Jane

2004-06-01

Physical Biology is a new peer-reviewed publication from Institute of Physics Publishing. Launched in 2004, the journal will foster the integration of biology with the traditionally more quantitative fields of physics, chemistry, computer science and other math-based disciplines. Its primary aim is to further the understanding of biological systems at all levels of complexity, ranging from the role of structure and dynamics of a single molecule to cellular networks and organisms. The journal encourages the development of a new biology-driven physics based on the extraordinary and increasingly rich data arising in biology, and provides research directions for those involved in the creation of novel bio-engineered systems. Physical Biology will publish a stimulating combination of full length research articles, communications, perspectives, reviews and tutorials from a wide range of disciplines covering topics such as: Single-molecule studies and nanobiotechnology Molecular interactions and protein folding Charge transfer and photobiology Ion channels; structure, function and ion regulation Molecular motors and force generation Subcellular processes Biological networks and neural systems Modeling aspects of molecular and cell biology Cell-cell signaling and interaction Biological patterns and development Evolutionary processes Novel tools and methods in physical biology Experts in the areas encompassed by the journal's scope have been appointed to the Editorial Scientific Committee and the composition of the Committee will be updated regularly to reflect the developments in this new and exciting field. Physical Biology is free online to everyone in 2004; you are invited to take advantage of this offer by visiting the journal homepage at http://physbio.iop.org This special print edition of Physical Biology is a combination of issues 1 and 2 of this electronic-only journal and it brings together an impressive range of articles in the fields covered, including a popular tutorial `An introduction to cell motility for the physical scientist' by D A Fletcher and J A Theriot. Physical Biology offers a number of benefits to the author including free publication (no page or color charges), free multimedia enhancements, rapid publication and a large international readership. To ensure that Physical Biology is truly interdisciplinary and accessible to readers across a broad range of fields, the journal ultilizes a style editor. This unique service makes the journal indispensible to biologists and physicists alike. The feedback from both readers and authors on the use of style editing has been positive: `it is unusual in my experience for a journal to provide such guidance and it augurs well for Physical Biology's role in bridging the gap between the physical and biological sciences' S S Andrews, Lawrence Berkeley Laboratory, USA. You are invited to join the growing list of authors by submitting your work to this new, cutting-edge and rigorously peer-reviewed journal.

Construction of new synthetic biology tools for the control of gene expression in the cyanobacterium Synechococcus sp. strain PCC 7002.

PubMed

Zess, Erin K; Begemann, Matthew B; Pfleger, Brian F

2016-02-01

Predictive control of gene expression is an essential tool for developing synthetic biological systems. The current toolbox for controlling gene expression in cyanobacteria is a barrier to more in-depth genetic analysis and manipulation. Towards relieving this bottleneck, this work describes the use of synthetic biology to construct an anhydrotetracycline-based induction system and adapt a trans-acting small RNA (sRNA) system for use in the cyanobacterium Synechococcus sp. strain PCC 7002. An anhydrotetracycline-inducible promoter was developed to maximize intrinsic strength and dynamic range. The resulting construct, PEZtet , exhibited tight repression and a maximum 32-fold induction upon addition of anhydrotetracycline. Additionally, a sRNA system based on the Escherichia coli IS10 RNA-IN/OUT regulator was adapted for use in Synechococcus sp. strain PCC 7002. This system exhibited 70% attenuation of target gene expression, providing a demonstration of the use of sRNAs for differential gene expression in cyanobacteria. These systems were combined to produce an inducible sRNA system, which demonstrated 59% attenuation of target gene expression. Lastly, the role of Hfq, a critical component of sRNA systems in E. coli, was investigated. Genetic studies showed that the Hfq homolog in Synechococcus sp. strain PCC 7002 did not impact repression by the engineered sRNA system. In summary, this work describes new synthetic biology tools that can be applied to physiological studies, metabolic engineering, or sRNA platforms in Synechococcus sp. strain PCC 7002. © 2015 Wiley Periodicals, Inc.

Sense and sensitivity in bioprocessing-detecting cellular metabolites with biosensors.

PubMed

Dekker, Linda; Polizzi, Karen M

2017-10-01

Biosensors use biological elements to detect or quantify an analyte of interest. In bioprocessing, biosensors are employed to monitor key metabolites. There are two main types: fully biological systems or biological recognition coupled with physical/chemical detection. New developments in chemical biosensors include multiplexed detection using microfluidics. Synthetic biology can be used to engineer new biological biosensors with improved characteristics. Although there have been few biosensors developed for bioprocessing thus far, emerging trends can be applied in the future. A range of new platform technologies will enable rapid engineering of new biosensors based on transcriptional activation, riboswitches, and Förster Resonance Energy Transfer. However, translation to industry remains a challenge and more research into the robustness biosensors at scale is needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

STOCHSIMGPU: parallel stochastic simulation for the Systems Biology Toolbox 2 for MATLAB.

PubMed

Klingbeil, Guido; Erban, Radek; Giles, Mike; Maini, Philip K

2011-04-15

The importance of stochasticity in biological systems is becoming increasingly recognized and the computational cost of biologically realistic stochastic simulations urgently requires development of efficient software. We present a new software tool STOCHSIMGPU that exploits graphics processing units (GPUs) for parallel stochastic simulations of biological/chemical reaction systems and show that significant gains in efficiency can be made. It is integrated into MATLAB and works with the Systems Biology Toolbox 2 (SBTOOLBOX2) for MATLAB. The GPU-based parallel implementation of the Gillespie stochastic simulation algorithm (SSA), the logarithmic direct method (LDM) and the next reaction method (NRM) is approximately 85 times faster than the sequential implementation of the NRM on a central processing unit (CPU). Using our software does not require any changes to the user's models, since it acts as a direct replacement of the stochastic simulation software of the SBTOOLBOX2. The software is open source under the GPL v3 and available at http://www.maths.ox.ac.uk/cmb/STOCHSIMGPU. The web site also contains supplementary information. klingbeil@maths.ox.ac.uk Supplementary data are available at Bioinformatics online.

An Ibm PC/AT-Based Image Acquisition And Processing System For Quantitative Image Analysis

NASA Astrophysics Data System (ADS)

Kim, Yongmin; Alexander, Thomas

1986-06-01

In recent years, a large number of applications have been developed for image processing systems in the area of biological imaging. We have already finished the development of a dedicated microcomputer-based image processing and analysis system for quantitative microscopy. The system's primary function has been to facilitate and ultimately automate quantitative image analysis tasks such as the measurement of cellular DNA contents. We have recognized from this development experience, and interaction with system users, biologists and technicians, that the increasingly widespread use of image processing systems, and the development and application of new techniques for utilizing the capabilities of such systems, would generate a need for some kind of inexpensive general purpose image acquisition and processing system specially tailored for the needs of the medical community. We are currently engaged in the development and testing of hardware and software for a fairly high-performance image processing computer system based on a popular personal computer. In this paper, we describe the design and development of this system. Biological image processing computer systems have now reached a level of hardware and software refinement where they could become convenient image analysis tools for biologists. The development of a general purpose image processing system for quantitative image analysis that is inexpensive, flexible, and easy-to-use represents a significant step towards making the microscopic digital image processing techniques more widely applicable not only in a research environment as a biologist's workstation, but also in clinical environments as a diagnostic tool.

Computational dynamic approaches for temporal omics data with applications to systems medicine.

PubMed

Liang, Yulan; Kelemen, Arpad

2017-01-01

Modeling and predicting biological dynamic systems and simultaneously estimating the kinetic structural and functional parameters are extremely important in systems and computational biology. This is key for understanding the complexity of the human health, drug response, disease susceptibility and pathogenesis for systems medicine. Temporal omics data used to measure the dynamic biological systems are essentials to discover complex biological interactions and clinical mechanism and causations. However, the delineation of the possible associations and causalities of genes, proteins, metabolites, cells and other biological entities from high throughput time course omics data is challenging for which conventional experimental techniques are not suited in the big omics era. In this paper, we present various recently developed dynamic trajectory and causal network approaches for temporal omics data, which are extremely useful for those researchers who want to start working in this challenging research area. Moreover, applications to various biological systems, health conditions and disease status, and examples that summarize the state-of-the art performances depending on different specific mining tasks are presented. We critically discuss the merits, drawbacks and limitations of the approaches, and the associated main challenges for the years ahead. The most recent computing tools and software to analyze specific problem type, associated platform resources, and other potentials for the dynamic trajectory and interaction methods are also presented and discussed in detail.

Data processing, multi-omic pathway mapping, and metabolite activity analysis using XCMS Online

PubMed Central

Forsberg, Erica M; Huan, Tao; Rinehart, Duane; Benton, H Paul; Warth, Benedikt; Hilmers, Brian; Siuzdak, Gary

2018-01-01

Systems biology is the study of complex living organisms, and as such, analysis on a systems-wide scale involves the collection of information-dense data sets that are representative of an entire phenotype. To uncover dynamic biological mechanisms, bioinformatics tools have become essential to facilitating data interpretation in large-scale analyses. Global metabolomics is one such method for performing systems biology, as metabolites represent the downstream functional products of ongoing biological processes. We have developed XCMS Online, a platform that enables online metabolomics data processing and interpretation. A systems biology workflow recently implemented within XCMS Online enables rapid metabolic pathway mapping using raw metabolomics data for investigating dysregulated metabolic processes. In addition, this platform supports integration of multi-omic (such as genomic and proteomic) data to garner further systems-wide mechanistic insight. Here, we provide an in-depth procedure showing how to effectively navigate and use the systems biology workflow within XCMS Online without a priori knowledge of the platform, including uploading liquid chromatography (LCLC)–mass spectrometry (MS) data from metabolite-extracted biological samples, defining the job parameters to identify features, correcting for retention time deviations, conducting statistical analysis of features between sample classes and performing predictive metabolic pathway analysis. Additional multi-omics data can be uploaded and overlaid with previously identified pathways to enhance systems-wide analysis of the observed dysregulations. We also describe unique visualization tools to assist in elucidation of statistically significant dysregulated metabolic pathways. Parameter input takes 5–10 min, depending on user experience; data processing typically takes 1–3 h, and data analysis takes ~30 min. PMID:29494574

Simultaneous biological nutrient removal: evaluation of autotrophic denitrification, heterotrophic nitrification, and biological phosphorus removal in full-scale systems.

PubMed

Littleton, Helen X; Daigger, Glen T; Strom, Peter F; Cowan, Robert A

2003-01-01

Simultaneous biological nutrient removal (SBNR) is the biological removal of nitrogen and phosphorus in excess of that required for biomass synthesis in a biological wastewater treatment system without defined anaerobic or anoxic zones. Evidence is growing that significant SBNR can occur in many systems, including the aerobic zone of systems already configured for biological nutrient removal. Although SBNR systems offer several potential advantages, they cannot be fully realized until the mechanisms responsible for SBNR are better understood. Consequently, a research program was initiated with the basic hypothesis that three mechanisms might be responsible for SBNR: the reactor macroenvironment, the floc microenvironment, and novel microorganisms. Previously, the nutrient removal capabilities of seven full-scale, staged, closed-loop bioreactors known as Orbal oxidation ditches were evaluated. Chemical analysis and microbiological observations suggested that SBNR occurred in these systems. Three of these plants were further examined in this research to evaluate the importance of novel microorganisms, especially for nitrogen removal. A screening tool was developed to determine the relative significance of the activities of microorganisms capable of autotrophic denitrification and heterotrophic nitrification-aerobic denitrification in biological nutrient removal systems. The results indicated that novel microorganisms were not substantial contributors to SBNR in the plants studied. Phosphorus metabolism (anaerobic release, aerobic uptake) was also tested in one of the plants. Activity within the mixed liquor that was consistent with current theories for phosphorus-accumulating organisms (PAOs) was observed. Along with other observations, this suggests the presence of PAOs in the facilities studied.

Biodiversity, Factor Endowments and National Security: The Next Great Game?

DTIC Science & Technology

2009-11-08

biomass, the genetic material of biological systems, that exist largely in the global south8 in biodiversity hotspots.9 Through the increasing use of...including pharmaceutical bio-prospecting, ethno-botanical bio-prospecting, botanical medicines, nano-technology, biological control and crop protection...production mainly focuses on material that is extracted from areas where biological diversity is highest, i.e. genetic material from 10 developing

Cooperative management of riparian forest habitats to maintain biological quality and ecosystem integrity

Treesearch

David Deardorff; Kathryn Wadsworth

1996-01-01

The New Mexico State Land Office has initiated a rare plant survey of state trust land, an inventory and assessment of riparian areas on the trust land, and the development of a biological resources data base and information management system. Some riparian sites that still belong to the trust have been negatively impacted by livestock such that biological quality and...

A functional approach to emotion in autonomous systems.

PubMed

Sanz, Ricardo; Hernández, Carlos; Gómez, Jaime; Hernando, Adolfo

2010-01-01

The construction of fully effective systems seems to pass through the proper exploitation of goal-centric self-evaluative capabilities that let the system teleologically self-manage. Emotions seem to provide this kind of functionality to biological systems and hence the interest in emotion for function sustainment in artificial systems performing in changing and uncertain environments; far beyond the media hullabaloo of displaying human-like emotion-laden faces in robots. This chapter provides a brief analysis of the scientific theories of emotion and presents an engineering approach for developing technology for robust autonomy by implementing functionality inspired in that of biological emotions.

Co-culture systems and technologies: taking synthetic biology to the next level.

PubMed

Goers, Lisa; Freemont, Paul; Polizzi, Karen M

2014-07-06

Co-culture techniques find myriad applications in biology for studying natural or synthetic interactions between cell populations. Such techniques are of great importance in synthetic biology, as multi-species cell consortia and other natural or synthetic ecology systems are widely seen to hold enormous potential for foundational research as well as novel industrial, medical and environmental applications with many proof-of-principle studies in recent years. What is needed for co-cultures to fulfil their potential? Cell-cell interactions in co-cultures are strongly influenced by the extracellular environment, which is determined by the experimental set-up, which therefore needs to be given careful consideration. An overview of existing experimental and theoretical co-culture set-ups in synthetic biology and adjacent fields is given here, and challenges and opportunities involved in such experiments are discussed. Greater focus on foundational technology developments for co-cultures is needed for many synthetic biology systems to realize their potential in both applications and answering biological questions. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

[Development and Application of Metabonomics in Forensic Toxicology].

PubMed

Yan, Hui; Shen, Min

2015-06-01

Metabonomics is an important branch of system biology following the development of genomics, transcriptomics and proteomics. It can perform high-throughput detection and data processing with multiple parameters, potentially enabling the identification and quantification of all small metabolites in a biological system. It can be used to provide comprehensive information on the toxicity effects, toxicological mechanisms and biomarkers, sensitively finding the unusual metabolic changes caused by poison. This article mainly reviews application of metabonomics in toxicological studies of abused drugs, pesticides, poisonous plants and poisonous animals, and also illustrates the new direction of forensic toxicology research.

Biological control of livestock pests: Pathogens

USDA-ARS?s Scientific Manuscript database

Interest in biological methods for livestock and poultry pest management is largely motivated by the development of resistance to most of the available synthetic pesticides by the major pests. There also has been a marked increase in organic systems, and those that promote animal welfare by reducing...

NASA Space Biology Program: 9th Annual Symposium

NASA Technical Reports Server (NTRS)

Halstead, T. W.

1985-01-01

Topics covered include plant and animal gravity receptors and transduction; the role of gravity in growth and development of plants and animals; biological support structures and the role of calcium; mechanisms and responses of gravity sensitive systems; and mechanisms of plant responses to gravity.

Opportunities and questions for the fundamental biological sciences in space

NASA Technical Reports Server (NTRS)

Sharp, Joseph C.; Vernikos, Joan

1992-01-01

The nature of biological issues which can be addressed during long-term space missions is briefly discussed. These issues include structure, from cell to organ to organism; function, the regulation of systems such as immunology, neural sciences, and behavior; and reproduction and development.

Biomedical experiments. Part A: Biostack experiment

NASA Technical Reports Server (NTRS)

Buecker, H.; Horneck, G.; Reinholz, E.; Scheuermann, W.; Ruether, W.; Graul, E. H.; Planel, H.; Soleilhavoup, J. P.; Cuer, P.; Kaiser, R.

1972-01-01

The biostack experiment is described which was designed to study the biologic effects of individual heavy nuclei of galactic cosmic radiation during space flight outside the magnetosphere of the earth. Specifically, the biostack experiment was designed to promote research on the effects of high energy/high Z particles of galactic cosmic radiation on a broad spectrum of biologic systems, from the molecular to the highly organized and developed forms of life. The experiment was considered unique and scientifically meritorious because of its potential yield of information - currently unavailable on earth - on the interaction of biologic systems with the heavy particles of galactic cosmic radiation.

The National Biological Information Infrastructure: Coming of age

USGS Publications Warehouse

Cotter, G.; Frame, M.; Sepic, R.; Zolly, L.

2000-01-01

Coordinated by the US Geological Survey, the National Biological Information Infrastructure (NBII) is a Web-based system that provides increased access to data and information on the nation's biological resources. The NBII can be viewed from a variety of perspectives. This article - an individual case study and not a broad survey with extensive references to the literature - addresses the structure of the NBII related to thematic sections, infrastructure sections and place-based sections, and other topics such as the Integrated Taxonomic Information System (one of our more innovative tools) and the development of our controlled vocabulary.

Systems Biology and Cancer Prevention: All Options on the Table

PubMed Central

Rosenfeld, Simon; Kapetanovic, Izet

2008-01-01

In this paper, we outline the status quo and approaches to further development of the systems biology concepts with focus on applications in cancer prevention science. We discuss the biological aspects of cancer research that are of primary importance in cancer prevention, motivations for their mathematical modeling and some recent advances in computational oncology. We also make an attempt to outline in big conceptual terms the contours of future work aimed at creation of large-scale computational and informational infrastructure for using as a routine tool in cancer prevention science and decision making. PMID:19787092

A systems-level approach for metabolic engineering of yeast cell factories.

PubMed

Kim, Il-Kwon; Roldão, António; Siewers, Verena; Nielsen, Jens

2012-03-01

The generation of novel yeast cell factories for production of high-value industrial biotechnological products relies on three metabolic engineering principles: design, construction, and analysis. In the last two decades, strong efforts have been put on developing faster and more efficient strategies and/or technologies for each one of these principles. For design and construction, three major strategies are described in this review: (1) rational metabolic engineering; (2) inverse metabolic engineering; and (3) evolutionary strategies. Independent of the selected strategy, the process of designing yeast strains involves five decision points: (1) choice of product, (2) choice of chassis, (3) identification of target genes, (4) regulating the expression level of target genes, and (5) network balancing of the target genes. At the construction level, several molecular biology tools have been developed through the concept of synthetic biology and applied for the generation of novel, engineered yeast strains. For comprehensive and quantitative analysis of constructed strains, systems biology tools are commonly used and using a multi-omics approach. Key information about the biological system can be revealed, for example, identification of genetic regulatory mechanisms and competitive pathways, thereby assisting the in silico design of metabolic engineering strategies for improving strain performance. Examples on how systems and synthetic biology brought yeast metabolic engineering closer to industrial biotechnology are described in this review, and these examples should demonstrate the potential of a systems-level approach for fast and efficient generation of yeast cell factories. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Systems genomics analysis centered on epigenetic inheritance supports development of a unified theory of biology.

PubMed

Sharma, Abhay

2015-11-01

New discoveries are increasingly demanding integration of epigenetics, molecular biology, genomic networks and physiology with evolution. This article provides a proof of concept for evolutionary transgenerational systems biology, proposed recently in the context of epigenetic inheritance in mammals. Gene set enrichment analysis of available genome-level mammalian data presented here seem consistent with the concept that: (1) heritable information about environmental effects in somatic cells is communicated to the germline by circulating microRNAs (miRNAs) or other RNAs released in physiological fluids; (2) epigenetic factors including miRNA-like small RNAs, DNA methylation and histone modifications are propagated across generations via gene networks; and (3) inherited epigenetic variations in the form of methylated cytosines are fixed in the population as thymines over the evolutionary time course. The analysis supports integration of physiology and epigenetics with inheritance and evolution. This may catalyze efforts to develop a unified theory of biology. © 2015. Published by The Company of Biologists Ltd.

Analytic considerations and axiomatic approaches to the concept cell death and cell survival functions in biology and cancer treatment.

PubMed

Gkigkitzis, Ioannis; Haranas, Ioannis; Austerlitz, Carlos

2015-01-01

This study contains a discussion on the connection between current mathematical and biological modeling systems in response to the main research need for the development of a new mathematical theory for study of cell survival after medical treatment and cell biological behavior in general. This is a discussion of suggested future research directions and relations with interdisciplinary science. In an effort to establish the foundations for a possible framework that may be adopted to study and analyze the process of cell survival during treatment, we investigate the organic connection among an axiomatic system foundation, a predator-prey rate equation, and information theoretic signal processing. A new set theoretic approach is also introduced through the definition of cell survival units or cell survival units indicating the use of "proper classes" according to the Zermelo-Fraenkel set theory and the axiom of choice, as the mathematics appropriate for the development of biological theory of cell survival.

Cancer systems biology: signal processing for cancer research

PubMed Central

Yli-Harja, Olli; Ylipää, Antti; Nykter, Matti; Zhang, Wei

2011-01-01

In this editorial we introduce the research paradigms of signal processing in the era of systems biology. Signal processing is a field of science traditionally focused on modeling electronic and communications systems, but recently it has turned to biological applications with astounding results. The essence of signal processing is to describe the natural world by mathematical models and then, based on these models, develop efficient computational tools for solving engineering problems. Here, we underline, with examples, the endless possibilities which arise when the battle-hardened tools of engineering are applied to solve the problems that have tormented cancer researchers. Based on this approach, a new field has emerged, called cancer systems biology. Despite its short history, cancer systems biology has already produced several success stories tackling previously impracticable problems. Perhaps most importantly, it has been accepted as an integral part of the major endeavors of cancer research, such as analyzing the genomic and epigenomic data produced by The Cancer Genome Atlas (TCGA) project. Finally, we show that signal processing and cancer research, two fields that are seemingly distant from each other, have merged into a field that is indeed more than the sum of its parts. PMID:21439242

Echinococcus as a model system: biology and epidemiology.

PubMed

Thompson, R C A; Jenkins, D J

2014-10-15

The introduction of Echinococcus to Australia over 200 years ago and its establishment in sheep rearing areas of the country inflicted a serious medical and economic burden on the country. This resulted in an investment in both basic and applied research aimed at learning more about the biology and life cycle of Echinococcus. This research served to illustrate the uniqueness of the parasite in terms of developmental biology and ecology, and the value of Echinococcus as a model system in a broad range of research, from fundamental biology to theoretical control systems. These studies formed the foundation for an international, diverse and ongoing research effort on the hydatid organisms encompassing stem cell biology, gene regulation, strain variation, wildlife diseases and models of transmission dynamics. We describe the development, nature and diversity of this research, and how it was initiated in Australia but subsequently has stimulated much international and collaborative research on Echinococcus. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Systems metabolic engineering in an industrial setting.

PubMed

Sagt, Cees M J

2013-03-01

Systems metabolic engineering is based on systems biology, synthetic biology, and evolutionary engineering and is now also applied in industry. Industrial use of systems metabolic engineering focuses on strain and process optimization. Since ambitious yields, titers, productivities, and low costs are key in an industrial setting, the use of effective and robust methods in systems metabolic engineering is becoming very important. Major improvements in the field of proteomics and metabolomics have been crucial in the development of genome-wide approaches in strain and process development. This is accompanied by a rapid increase in DNA sequencing and synthesis capacity. These developments enable the use of systems metabolic engineering in an industrial setting. Industrial systems metabolic engineering can be defined as the combined use of genome-wide genomics, transcriptomics, proteomics, and metabolomics to modify strains or processes. This approach has become very common since the technology for generating large data sets of all levels of the cellular processes has developed quite fast into robust, reliable, and affordable methods. The main challenge and scope of this mini review is how to translate these large data sets in relevant biological leads which can be tested for strain or process improvements. Experimental setup, heterogeneity of the culture, and sample pretreatment are important issues which are easily underrated. In addition, the process of structuring, filtering, and visualization of data is important, but also, the availability of a genetic toolbox and equipment for medium/high-throughput fermentation is a key success factor. For an efficient bioprocess, all the different components in this process have to work together. Therefore, mutual tuning of these components is an important strategy.

Quantitative Analysis of the Trends Exhibited by the Three Interdisciplinary Biological Sciences: Biophysics, Bioinformatics, and Systems Biology.

PubMed

Kang, Jonghoon; Park, Seyeon; Venkat, Aarya; Gopinath, Adarsh

2015-12-01

New interdisciplinary biological sciences like bioinformatics, biophysics, and systems biology have become increasingly relevant in modern science. Many papers have suggested the importance of adding these subjects, particularly bioinformatics, to an undergraduate curriculum; however, most of their assertions have relied on qualitative arguments. In this paper, we will show our metadata analysis of a scientific literature database (PubMed) that quantitatively describes the importance of the subjects of bioinformatics, systems biology, and biophysics as compared with a well-established interdisciplinary subject, biochemistry. Specifically, we found that the development of each subject assessed by its publication volume was well described by a set of simple nonlinear equations, allowing us to characterize them quantitatively. Bioinformatics, which had the highest ratio of publications produced, was predicted to grow between 77% and 93% by 2025 according to the model. Due to the large number of publications produced in bioinformatics, which nearly matches the number published in biochemistry, it can be inferred that bioinformatics is almost equal in significance to biochemistry. Based on our analysis, we suggest that bioinformatics be added to the standard biology undergraduate curriculum. Adding this course to an undergraduate curriculum will better prepare students for future research in biology.

Near-infrared Raman spectroscopy of single optically trapped biological cells

NASA Astrophysics Data System (ADS)

Xie, Changan; Dinno, Mumtaz A.; Li, Yong-Qing

2002-02-01

We report on the development and testing of a compact laser tweezers Raman spectroscopy (LTRS) system. The system combines optical trapping and near-infrared Raman spectroscopy for manipulation and identification of single biological cells in solution. A low-power diode laser at 785 nm was used for both trapping and excitation for Raman spectroscopy of the suspended microscopic particles. The design of the LTRS system provides high sensitivity and permits real-time spectroscopic measurements of the biological sample. The system was calibrated by use of polystyrene microbeads and tested on living blood cells and on both living and dead yeast cells. As expected, different images and Raman spectra were observed for the different cells. The LTRS system may provide a valuable tool for the study of fundamental cellular processes and the diagnosis of cellular disorders.

Traceability in stem cell research: from participant sample to induced pluripotent stem cell and back.

PubMed

Morrison, Michael; Moraia, Linda Briceño; Steele, Jane C

2016-01-01

This paper describes a traceability system developed for the Stem cells for Biological Assays of Novel drugs and prediCtive toxiCology consortium. The system combines records and labels that to biological material across geographical locations and scientific processes from sample donation to induced pluripotent stem cell line. The labeling system uses a unique identification number to link every aliquot of sample at every stage of the reprogramming pathway back to the original donor. Only staff at the clinical recruitment site can reconnect the unique identification number to the identifying details of a specific donor. This ensures the system meets ethical and legal requirements for protecting privacy while allowing full traceability of biological material. The system can be adapted to other projects and for use with different primary sample types.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mann, Reinhold C.

This is the first formal progress report issued by the ORNL Life Sciences Division. It covers the period from February 1997 through December 1998, which has been critical in the formation of our new division. The legacy of 50 years of excellence in biological research at ORNL has been an important driver for everyone in the division to do their part so that this new research division can realize the potential it has to make seminal contributions to the life sciences for years to come. This reporting period is characterized by intense assessment and planning efforts. They included thorough scrutinymore » of our strengths and weaknesses, analyses of our situation with respect to comparative research organizations, and identification of major thrust areas leading to core research efforts that take advantage of our special facilities and expertise. Our goal is to develop significant research and development (R&D) programs in selected important areas to which we can make significant contributions by combining our distinctive expertise and resources in the biological sciences with those in the physical, engineering, and computational sciences. Significant facilities in mouse genomics, mass spectrometry, neutron science, bioanalytical technologies, and high performance computing are critical to the success of our programs. Research and development efforts in the division are organized in six sections. These cluster into two broad areas of R&D: systems biology and technology applications. The systems biology part of the division encompasses our core biological research programs. It includes the Mammalian Genetics and Development Section, the Biochemistry and Biophysics Section, and the Computational Biosciences Section. The technology applications part of the division encompasses the Assessment Technology Section, the Environmental Technology Section, and the Toxicology and Risk Analysis Section. These sections are the stewards of the division's core competencies. The common mission of the division is to advance science and technology to understand complex biological systems and their relationship with human health and the environment.« less

The plant vascular system: Evolution, development and functions

USDA-ARS?s Scientific Manuscript database

The emergence of the tracheophyte-based vascular system of land plants had major impacts on the evolution of terrestrial biology, in general, through its role in facilitating the development of plants with increased stature, photosynthetic output, and ability to colonize a greatly expanded range of ...

Blueprints for green biotech: development and application of standards for plant synthetic biology.

PubMed

Patron, Nicola J

2016-06-15

Synthetic biology aims to apply engineering principles to the design and modification of biological systems and to the construction of biological parts and devices. The ability to programme cells by providing new instructions written in DNA is a foundational technology of the field. Large-scale de novo DNA synthesis has accelerated synthetic biology by offering custom-made molecules at ever decreasing costs. However, for large fragments and for experiments in which libraries of DNA sequences are assembled in different combinations, assembly in the laboratory is still desirable. Biological assembly standards allow DNA parts, even those from multiple laboratories and experiments, to be assembled together using the same reagents and protocols. The adoption of such standards for plant synthetic biology has been cohesive for the plant science community, facilitating the application of genome editing technologies to plant systems and streamlining progress in large-scale, multi-laboratory bioengineering projects. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

The Chemo-Biological Outreach of Nano-Biomaterials: Implications for Tissue Engineering and Regenerative Medicine.

PubMed

Kumar, Pradeep; Choonara, Yahya E; Khan, Riaz A; Pillay, Viness

2017-01-01

Nanobiomaterials can be defined as materials interacting with and influencing the biological microenvironment at a nanointerface. Recently the basic as well as applied research related to nanobiomaterials - a conjugation of nano-, material- and life-sciences - has immensely evolved for therapeutics and related biotechnology areas. The current overview focused on the potential of nanobiomaterial-based substrates towards the generation of biocompatible surfaces, tissue engineering architectures, and regenerative medicine. Emphasis was given to chemomolecular functionalization of nanobiomaterials, nanobiomaterial composites, and morphomechanically modified nanoarchetypes and their inherent chemo-biological interaction with the biological microenvironment. Additionally, recent developments in nanobiomaterial substrate design and structure, chemo-biological interface related bio-systems uses and further evolving applications in health care, therapeutics and nanomedicine were discussed herein. Furthermore, a special emphasis was placed on the nano-chemo-biological interactions inherent to various nanobiomaterial substrates in close vicinity with biological systems. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Advances in Structural Biology and the Application to Biological Filament Systems.

PubMed

Popp, David; Koh, Fujiet; Scipion, Clement P M; Ghoshdastider, Umesh; Narita, Akihiro; Holmes, Kenneth C; Robinson, Robert C

2018-04-01

Structural biology has experienced several transformative technological advances in recent years. These include: development of extremely bright X-ray sources (microfocus synchrotron beamlines and free electron lasers) and the use of electrons to extend protein crystallography to ever decreasing crystal sizes; and an increase in the resolution attainable by cryo-electron microscopy. Here we discuss the use of these techniques in general terms and highlight their application for biological filament systems, an area that is severely underrepresented in atomic resolution structures. We assemble a model of a capped tropomyosin-actin minifilament to demonstrate the utility of combining structures determined by different techniques. Finally, we survey the methods that attempt to transform high resolution structural biology into more physiological environments, such as the cell. Together these techniques promise a compelling decade for structural biology and, more importantly, they will provide exciting discoveries in understanding the designs and purposes of biological machines. © 2018 The Authors. BioEssays Published by WILEY Periodicals, Inc.

Physical methods for investigating structural colours in biological systems

PubMed Central

Vukusic, P.; Stavenga, D.G.

2009-01-01

Many biological systems are known to use structural colour effects to generate aspects of their appearance and visibility. The study of these phenomena has informed an eclectic group of fields ranging, for example, from evolutionary processes in behavioural biology to micro-optical devices in technologically engineered systems. However, biological photonic systems are invariably structurally and often compositionally more elaborate than most synthetically fabricated photonic systems. For this reason, an appropriate gamut of physical methods and investigative techniques must be applied correctly so that the systems' photonic behaviour may be appropriately understood. Here, we survey a broad range of the most commonly implemented, successfully used and recently innovated physical methods. We discuss the costs and benefits of various spectrometric methods and instruments, namely scatterometers, microspectrophotometers, fibre-optic-connected photodiode array spectrometers and integrating spheres. We then discuss the role of the materials' refractive index and several of the more commonly used theoretical approaches. Finally, we describe the recent developments in the research field of photonic crystals and the implications for the further study of structural coloration in animals. PMID:19158009

The Histochemistry and Cell Biology omnium-gatherum: the year 2015 in review.

PubMed

Taatjes, Douglas J; Roth, Jürgen

2016-03-01

We provide here our annual review/synopsis of all of the articles published in Histochemistry and Cell Biology (HCB) for the preceding year. In 2015, HCB published 102 articles, representing a wide variety of topics and methodologies. For ease of access to these differing topics, we have created categories, as determined by the types of articles presented to provide a quick index representing the general areas covered. This year, these categories include: (1) advances in methodologies; (2) molecules in health and disease; (3) organelles, subcellular structures, and compartments; (4) the nucleus; (5) stem cells and tissue engineering; (6) cell cultures: properties and capabilities; (7) connective tissues and extracellular matrix; (8) developmental biology; (9) nervous system; (10) musculoskeletal system; (11) respiratory and cardiovascular system; (12) liver and gastrointestinal tract; and (13) male and female reproductive systems. Of note, the categories proceed from methods development, to molecules, intracellular compartments, stem cells and cell culture, extracellular matrix, developmental biology, and finishing with various organ systems, hopefully presenting a logical journey from methods to organismal molecules, cells, and whole tissue systems.

State-of-the-art exposure chamber for highly controlled and reproducible THz biological effects studies

NASA Astrophysics Data System (ADS)

Cerna, Cesario Z.; Elam, David P.; Echchgadda, Ibtissam; Sloan, Mark A.; Wilmink, Gerald J.

2014-03-01

Terahertz (THz) imaging and sensing technologies are increasingly being used at international airports for security screening purposes and at major medical centers for cancer and burn diagnosis. The emergence of new THz applications has directly resulted in an increased interest regarding the biological effects associated with this frequency range. Knowledge of THz biological effects is also desired for the safe use of THz systems, identification of health hazards, and development of empirically-based safety standards. In this study, we developed a state-of-the-art exposure chamber that allowed for highly controlled and reproducible studies of THz biological effects. This innovative system incorporated an industry grade cell incubator system that permitted a highly controlled exposure environment, where temperatures could be maintained at 37 °C +/- 0.1 °C, carbon dioxide (CO2) levels at 5% +/- 0.1%, and relative humidity (RH) levels at 95% +/- 1%. To maximize the THz power transmitted to the cell culture region inside the humid incubator, a secondary custom micro-chamber was fabricated and incorporated into the system. This micro-chamber shields the THz beam from the incubator environment and could be nitrogen-purged to eliminate water absorption effects. Additionally, a microscope that allowed for real-time visualization of the live cells before, during, and after THz exposure was integrated into the exposure system.

Biological and chemical terrorism scenarios and implications for detection systems needs

NASA Astrophysics Data System (ADS)

Gordon, Susanna P.; Chumfong, Isabelle; Edwards, Donna M.; Gleason, Nathaniel J.; West, Todd; Yang, Lynn

2007-04-01

Terrorists intent on causing many deaths and severe disruption to our society could, in theory, cause hundreds to tens of thousands of deaths and significant contamination of key urban facilities by using chemical or biological (CB) agents. The attacks that have occurred to date, such as the 1995 Aum Shinrikyo CB attacks and the 2001 anthrax letters, have been very small on the scale of what is possible. In order to defend against and mitigate the impacts of large-scale terrorist attacks, defensive systems for protection of urban areas and high-value facilities from biological and chemical threats have been deployed. This paper reviews analyses of such scenarios and of the efficacy of potential response options, discusses defensive systems that have been deployed and detectors that are being developed, and finally outlines the detection systems that will be needed for improved CB defense in the future. Sandia's collaboration with San Francisco International Airport on CB defense will also be briefly reviewed, including an overview of airport facility defense guidelines produced in collaboration with Lawrence Berkeley National Laboratory. The analyses that will be discussed were conducted by Sandia National Laboratories' Systems Studies Department in support of the U.S. Department of Homeland Security (DHS) Science and Technology Directorate, and include quantitative analyses utilizing simulation models developed through close collaboration with subject matter experts, such as public health officials in urban areas and biological defense experts.

Space biology research development

NASA Technical Reports Server (NTRS)

Bonting, Sjoerd L.

1993-01-01

The purpose of the Search for Extraterrestrial Intelligence (SETI) Institute is to conduct and promote research related activities regarding the search for extraterrestrial life, particularly intelligent life. Such research encompasses the broad discipline of 'Life in the Universe', including all scientific and technological aspects of astronomy and the planetary sciences, chemical evolution, the origin of life, biological evolution, and cultural evolution. The primary purpose was to provide funding for the Principal Investigator to collaborate with the personnel of the SETI Institute and the NASA-Ames Research center in order to plan and develop space biology research on and in connection with Space Station Freedom; to promote cooperation with the international partners in the space station; to conduct a study on the use of biosensors in space biology research and life support system operation; and to promote space biology research through the initiation of an annual publication 'Advances in Space Biology and Medicine'.

[Classification of organisms and structuralism in biology].

PubMed

Vasil'eva, L I

2001-01-01

Structuralism in biology is the oldest trend oriented to the search for natural "laws of forms" comparable with laws of growth of crystal, was revived at the end of 20th century on the basis of structuralist thought in socio-humanitarian sciences. The development of principal ideas of the linguistic structuralism in some aspects is similar to that of biological systematics, especially concerning the relationships between "system" and "evolution". However, apart from this general similarity, biological structuralism is strongly focused on familiar problems of the origin of diversity in nature. In their striving for the renovation of existing views, biological structuralists oppose the neo-darwinism emphasizing the existence of "law of forms", that are independent on heredity and genetic "determinism". The trend to develop so-called "rational taxonomy" is also characteristic of biological structuralism but this attempt failed being connected neither with Darwin's historicism nor with Plato's typology.

Indoor Air Nuclear, Biological, and Chemical Health Modeling and Assessment System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stenner, Robert D.; Hadley, Donald L.; Armstrong, Peter R.

2001-03-01

Indoor air quality effects on human health are of increasing concern to public health agencies and building owners. The prevention and treatment of 'sick building' syndrome and the spread of air-borne diseases in hospitals, for example, are well known priorities. However, increasing attention is being directed to the vulnerability of our public buildings/places, public security and national defense facilities to terrorist attack or the accidental release of air-borne biological pathogens, harmful chemicals, or radioactive contaminants. The Indoor Air Nuclear, Biological, and Chemical Health Modeling and Assessment System (IA-NBC-HMAS) was developed to serve as a health impact analysis tool for usemore » in addressing these concerns. The overall goal was to develop a user-friendly fully functional prototype Health Modeling and Assessment system, which will operate under the PNNL FRAMES system for ease of use and to maximize its integration with other modeling and assessment capabilities accessible within the FRAMES system (e.g., ambient air fate and transport models, water borne fate and transport models, Physiologically Based Pharmacokinetic models, etc.). The prototype IA-NBC-HMAS is designed to serve as a functional Health Modeling and Assessment system that can be easily tailored to meet specific building analysis needs of a customer. The prototype system was developed and tested using an actual building (i.e., the Churchville Building located at the Aberdeen Proving Ground) and release scenario (i.e., the release and measurement of tracer materials within the building) to ensure realism and practicality in the design and development of the prototype system. A user-friendly "demo" accompanies this report to allow the reader the opportunity for a "hands on" review of the prototype system's capability.« less

Automated Miniaturized Instrument for Space Biology Applications and the Monitoring of the Astronauts Health Onboard the ISS

NASA Technical Reports Server (NTRS)

Karouia, Fathi; Peyvan, Kia; Danley, David; Ricco, Antonio J.; Santos, Orlando; Pohorille, Andrew

2011-01-01

Human space travelers experience a unique environment that affects homeostasis and physiologic adaptation. The spacecraft environment subjects the traveler to noise, chemical and microbiological contaminants, increased radiation, and variable gravity forces. As humans prepare for long-duration missions to the International Space Station (ISS) and beyond, effective measures must be developed, verified and implemented to ensure mission success. Limited biomedical quantitative capabilities are currently available onboard the ISS. Therefore, the development of versatile instruments to perform space biological analysis and to monitor astronauts' health is needed. We are developing a fully automated, miniaturized system for measuring gene expression on small spacecraft in order to better understand the influence of the space environment on biological systems. This low-cost, low-power, multi-purpose instrument represents a major scientific and technological advancement by providing data on cellular metabolism and regulation. The current system will support growth of microorganisms, extract and purify the RNA, hybridize it to the array, read the expression levels of a large number of genes by microarray analysis, and transmit the measurements to Earth. The system will help discover how bacteria develop resistance to antibiotics and how pathogenic bacteria sometimes increase their virulence in space, facilitating the development of adequate countermeasures to decrease risks associated with human spaceflight. The current stand-alone technology could be used as an integrated platform onboard the ISS to perform similar genetic analyses on any biological systems from the tree of life. Additionally, with some modification the system could be implemented to perform real-time in-situ microbial monitoring of the ISS environment (air, surface and water samples) and the astronaut's microbiome using 16SrRNA microarray technology. Furthermore, the current system can be enhanced substantially by combining it with other technologies for automated, miniaturized, high-throughput biological measurements, such as fast sequencing, protein identification (proteomics) and metabolite profiling (metabolomics). Thus, the system can be integrated with other biomedical instruments in order to support and enhance telemedicine capability onboard ISS. NASA's mission includes sustained investment in critical research leading to effective countermeasures to minimize the risks associated with human spaceflight, and the use of appropriate technology to sustain space exploration at reasonable cost. Our integrated microarray technology is expected to fulfill these two critical requirements and to enable the scientific community to better understand and monitor the effects of the space environment on microorganisms and on the astronaut, in the process leveraging current capabilities and overcoming present limitations.

Improving integrative searching of systems chemical biology data using semantic annotation.

PubMed

Chen, Bin; Ding, Ying; Wild, David J

2012-03-08

Systems chemical biology and chemogenomics are considered critical, integrative disciplines in modern biomedical research, but require data mining of large, integrated, heterogeneous datasets from chemistry and biology. We previously developed an RDF-based resource called Chem2Bio2RDF that enabled querying of such data using the SPARQL query language. Whilst this work has proved useful in its own right as one of the first major resources in these disciplines, its utility could be greatly improved by the application of an ontology for annotation of the nodes and edges in the RDF graph, enabling a much richer range of semantic queries to be issued. We developed a generalized chemogenomics and systems chemical biology OWL ontology called Chem2Bio2OWL that describes the semantics of chemical compounds, drugs, protein targets, pathways, genes, diseases and side-effects, and the relationships between them. The ontology also includes data provenance. We used it to annotate our Chem2Bio2RDF dataset, making it a rich semantic resource. Through a series of scientific case studies we demonstrate how this (i) simplifies the process of building SPARQL queries, (ii) enables useful new kinds of queries on the data and (iii) makes possible intelligent reasoning and semantic graph mining in chemogenomics and systems chemical biology. Chem2Bio2OWL is available at http://chem2bio2rdf.org/owl. The document is available at http://chem2bio2owl.wikispaces.com.

Systems biology for understanding and engineering of heterotrophic oleaginous microorganisms.

PubMed

Park, Beom Gi; Kim, Minsuk; Kim, Joonwon; Yoo, Heewang; Kim, Byung-Gee

2017-01-01

Heterotrophic oleaginous microorganisms continue to draw interest as they can accumulate a large amount of lipids which is a promising feedstock for the production of biofuels and oleochemicals. Nutrient limitation, especially nitrogen limitation, is known to effectively trigger the lipid production in these microorganisms. For the aim of developing improved strains, the mechanisms behind the lipid production have been studied for a long time. Nowadays, system-level understanding of their metabolism and associated metabolic switches is attainable with modern systems biology tools. This work reviews the systems biology studies, based on (i) top-down, large-scale 'omics' tools, and (ii) bottom-up, mathematical modeling methods, on the heterotrophic oleaginous microorganisms with an emphasis on further application to metabolic engineering. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design control considerations for biologic-device combination products.

PubMed

Anderson, Dave; Liu, Roger; Anand Subramony, J; Cammack, Jon

2017-03-01

Combination products are therapeutic and diagnostic medical products that combine drugs, devices, and/or biological products with one another. Historically, biologics development involved identifying efficacious doses administered to patients intravenously or perhaps by a syringe. Until fairly recently, there has been limited focus on developing an accompanying medical device, such as a prefilled syringe or auto-injector, to enable easy and more efficient delivery. For the last several years, and looking forward, where there may be little to distinguish biologics medicines with relatively similar efficacy profiles, the biotechnology market is beginning to differentiate products by patient-focused, biologic-device based combination products. As innovative as biologic-device combination products are, they can pose considerable development, regulatory, and commercialization challenges due to unique physicochemical properties and special clinical considerations (e.g., dosing volumes, frequency, co-medications, etc.) of the biologic medicine. A biologic-device combination product is a marriage between two partners with "cultural differences," so to speak. There are clear differences in the development, review, and commercialization processes of the biologic and the device. When these two cultures come together in a combination product, developers and reviewers must find ways to address the design controls and risk management processes of both the biologic and device, and knit them into a single entity with supporting product approval documentation. Moreover, digital medicine and connected health trends are pushing the boundaries of combination product development and regulations even further. Despite an admirable cooperation between industry and FDA in recent years, unique product configurations and design features have resulted in review challenges. These challenges have prompted agency reviewers to modernize consultation processes, while at the same time, promoting development of innovative, safe and effective combination products. It remains the manufacturer's responsibility to comply with the relevant requirements and regulations, and develop good business practices that clearly describe how these practices comply with FDA's final rule (21 CFR Part 4) and aligns with the company's already established quality system. Copyright © 2017 Elsevier B.V. All rights reserved.

SynBioSS-aided design of synthetic biological constructs.

PubMed

Kaznessis, Yiannis N

2011-01-01

We present walkthrough examples of using SynBioSS to design, model, and simulate synthetic gene regulatory networks. SynBioSS stands for Synthetic Biology Software Suite, a platform that is publicly available with Open Licenses at www.synbioss.org. An important aim of computational synthetic biology is the development of a mathematical modeling formalism that is applicable to a wide variety of simple synthetic biological constructs. SynBioSS-based modeling of biomolecular ensembles that interact away from the thermodynamic limit and not necessarily at steady state affords for a theoretical framework that is generally applicable to known synthetic biological systems, such as bistable switches, AND gates, and oscillators. Here, we discuss how SynBioSS creates links between DNA sequences and targeted dynamic phenotypes of these simple systems. Copyright © 2011 Elsevier Inc. All rights reserved.

Emerging systems biology approaches in nanotoxicology: Towards a mechanism-based understanding of nanomaterial hazard and risk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Costa, Pedro M.; Fadeel, Bengt, E-mail: Bengt.Fade

Engineered nanomaterials are being developed for a variety of technological applications. However, the increasing use of nanomaterials in society has led to concerns about their potential adverse effects on human health and the environment. During the first decade of nanotoxicological research, the realization has emerged that effective risk assessment of the multitudes of new nanomaterials would benefit from a comprehensive understanding of their toxicological mechanisms, which is difficult to achieve with traditional, low-throughput, single end-point oriented approaches. Therefore, systems biology approaches are being progressively applied within the nano(eco)toxicological sciences. This novel paradigm implies that the study of biological systems shouldmore » be integrative resulting in quantitative and predictive models of nanomaterial behaviour in a biological system. To this end, global ‘omics’ approaches with which to assess changes in genes, proteins, metabolites, etc. are deployed allowing for computational modelling of the biological effects of nanomaterials. Here, we highlight omics and systems biology studies in nanotoxicology, aiming towards the implementation of a systems nanotoxicology and mechanism-based risk assessment of nanomaterials. - Highlights: • Systems nanotoxicology is a multi-disciplinary approach to quantitative modelling. • Transcriptomics, proteomics and metabolomics remain the most common methods. • Global “omics” techniques should be coupled to computational modelling approaches. • The discovery of nano-specific toxicity pathways and biomarkers is a prioritized goal. • Overall, experimental nanosafety research must endeavour reproducibility and relevance.« less

Advances on plant-pathogen interactions from molecular toward systems biology perspectives.

PubMed

Peyraud, Rémi; Dubiella, Ullrich; Barbacci, Adelin; Genin, Stéphane; Raffaele, Sylvain; Roby, Dominique

2017-05-01

In the past 2 decades, progress in molecular analyses of the plant immune system has revealed key elements of a complex response network. Current paradigms depict the interaction of pathogen-secreted molecules with host target molecules leading to the activation of multiple plant response pathways. Further research will be required to fully understand how these responses are integrated in space and time, and exploit this knowledge in agriculture. In this review, we highlight systems biology as a promising approach to reveal properties of molecular plant-pathogen interactions and predict the outcome of such interactions. We first illustrate a few key concepts in plant immunity with a network and systems biology perspective. Next, we present some basic principles of systems biology and show how they allow integrating multiomics data and predict cell phenotypes. We identify challenges for systems biology of plant-pathogen interactions, including the reconstruction of multiscale mechanistic models and the connection of host and pathogen models. Finally, we outline studies on resistance durability through the robustness of immune system networks, the identification of trade-offs between immunity and growth and in silico plant-pathogen co-evolution as exciting perspectives in the field. We conclude that the development of sophisticated models of plant diseases incorporating plant, pathogen and climate properties represent a major challenge for agriculture in the future. © 2016 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

Strategies for drug delivery to the central nervous system by systemic route.

PubMed

Kasinathan, Narayanan; Jagani, Hitesh V; Alex, Angel Treasa; Volety, Subrahmanyam M; Rao, J Venkata

2015-05-01

Delivery of a drug into the central nervous system (CNS) is considered difficult. Most of the drugs discovered over the past decade are biological, which are high in molecular weight and polar in nature. The delivery of such drugs across the blood-brain barrier presents problems. This review discusses some of the options available to reach the CNS by systemic route. The focus is mainly on the recent developments in systemic delivery of a drug to the CNS. Databases such as Scopus, Google scholar, Science Direct, SciFinder and online journals were referred for preparing this article including 89 references. There are at least nine strategies that could be adopted to achieve the required drug concentration in the CNS. The recent developments in drug delivery are very promising to deliver biologicals into the CNS.

Biologically inspired autonomous structural materials with controlled toughening and healing

NASA Astrophysics Data System (ADS)

Garcia, Michael E.; Sodano, Henry A.

2010-04-01

The field of structural health monitoring (SHM) has made significant contributions in the field of prognosis and damage detection in the past decade. The advantageous use of this technology has not been integrated into operational structures to prevent damage from propagating or to heal injured regions under real time loading conditions. Rather, current systems relay this information to a central processor or human operator, who then determines a course of action such as altering the mission or scheduling repair maintenance. Biological systems exhibit advanced sensory and healing traits that can be applied to the design of material systems. For instance, bone is the major structural component in vertebrates; however, unlike modern structural materials, bone has many properties that make it effective for arresting the propagation of cracks and subsequent healing of the fractured area. The foremost goal for the development of future adaptive structures is to mimic biological systems, similar to bone, such that the material system can detect damage and deploy defensive traits to impede damage from propagating, thus preventing catastrophic failure while in operation. After sensing and stalling the propagation of damage, the structure must then be repaired autonomously using self healing mechanisms motivated by biological systems. Here a novel autonomous system is developed using shape memory polymers (SMPs), that employs an optical fiber network as both a damage detection sensor and a network to deliver stimulus to the damage site initiating adaptation and healing. In the presence of damage the fiber optic fractures allowing a high power laser diode to deposit a controlled level of thermal energy at the fractured sight locally reducing the modulus and blunting the crack tip, which significantly slows the crack growth rate. By applying a pre-induced strain field and utilizing the shape memory recovery effect, thermal energy can be deployed to close the crack and return the system to its original operating state. The entire system will effectively detect, self toughen, and subsequently heal damage as biological materials such as bone does.

Continuous sterilization of plumbing systems

NASA Technical Reports Server (NTRS)

Bryan, C. J.; Moyers, C. V.; Wright, E. E., Jr.

1979-01-01

Continuous sterilization of plumbing, such as in hospitals, clinics, and biological testing laboratories is possible with ethylene oxide/Freon 12 (ETO/F-12) humidifier developed for sterilization of potable water systems.

Early 20th-century research at the interfaces of genetics, development, and evolution: reflections on progress and dead ends.

PubMed

Deichmann, Ute

2011-09-01

Three early 20th-century attempts at unifying separate areas of biology, in particular development, genetics, physiology, and evolution, are compared in regard to their success and fruitfulness for further research: Jacques Loeb's reductionist project of unifying approaches by physico-chemical explanations; Richard Goldschmidt's anti-reductionist attempts to unify by integration; and Sewall Wright's combination of reductionist research and vision of hierarchical genetic systems. Loeb's program, demanding that all aspects of biology, including evolution, be studied by the methods of the experimental sciences, proved highly successful and indispensible for higher level investigations, even though evolutionary change and properties of biological systems up to now cannot be fully explained on the molecular level alone. Goldschmidt has been appraised as pioneer of physiological and developmental genetics and of a new evolutionary synthesis which transcended neo-Darwinism. However, this study concludes that his anti-reductionist attempts to integrate genetics, development and evolution have to be regarded as failures or dead ends. His grand speculations were based on the one hand on concepts and experimental systems that were too vague in order to stimulate further research, and on the other on experiments which in their core parts turned out not to be reproducible. In contrast, Sewall Wright, apart from being one of the architects of the neo-Darwinian synthesis of the 1930s, opened up new paths of testable quantitative developmental genetic investigations. He placed his research within a framework of logical reasoning, which resulted in the farsighted speculation that examinations of biological systems should be related to the regulation of hierarchical genetic subsystems, possibly providing a mechanism for development and evolution. I argue that his suggestion of basing the study of systems on clearly defined properties of the components has proved superior to Goldschmidt's approach of studying systems as a whole, and that attempts to integrate different fields at a too early stage may prove futile or worse. Copyright © 2011 Elsevier Inc. All rights reserved.

Cellular Gauge Symmetry and the Li Organization Principle: A Mathematical Addendum. Quantifying energetic dynamics in physical and biological systems through a simple geometric tool and geodetic curves.

PubMed

Yurkin, Alexander; Tozzi, Arturo; Peters, James F; Marijuán, Pedro C

2017-12-01

The present Addendum complements the accompanying paper "Cellular Gauge Symmetry and the Li Organization Principle"; it illustrates a recently-developed geometrical physical model able to assess electronic movements and energetic paths in atomic shells. The model describes a multi-level system of circular, wavy and zigzag paths which can be projected onto a horizontal tape. This model ushers in a visual interpretation of the distribution of atomic electrons' energy levels and the corresponding quantum numbers through rather simple tools, such as compasses, rulers and straightforward calculations. Here we show how this geometrical model, with the due corrections, among them the use of geodetic curves, might be able to describe and quantify the structure and the temporal development of countless physical and biological systems, from Langevin equations for random paths, to symmetry breaks occurring ubiquitously in physical and biological phenomena, to the relationships among different frequencies of EEG electric spikes. Therefore, in our work we explore the possible association of binomial distribution and geodetic curves configuring a uniform approach for the research of natural phenomena, in biology, medicine or the neurosciences. Copyright © 2017 Elsevier Ltd. All rights reserved.

Applications of systems biology towards microbial fuel production.

PubMed

Gowen, Christopher M; Fong, Stephen S

2011-10-01

Harnessing the immense natural diversity of biological functions for economical production of fuel has enormous potential benefits. Inevitably, however, the native capabilities for any given organism must be modified to increase the productivity or efficiency of a biofuel bioprocess. From a broad perspective, the challenge is to sufficiently understand the details of cellular functionality to be able to prospectively predict and modify the cellular function of a microorganism. Recent advances in experimental and computational systems biology approaches can be used to better understand cellular level function and guide future experiments. With pressure to quickly develop viable, renewable biofuel processes a balance must be maintained between obtaining depth of biological knowledge and applying that knowledge. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Problem-Solving Environment for Biological Network Informatics: Bio-Spice

DTIC Science & Technology

2007-06-01

user an environment to access software tools. The Dashboard is built upon the NetBeans Integrated Development Environment (IDE), an open source Java...based integration platform was demonstrated. During the subsequent six month development cycle, the first version of the NetBeans based Bio-SPICE...frameworks (OAA, NetBeans , and Systems Biology Workbench (SBW)[15]), it becomes possible for Bio-SPICE tools to truly interoperate. This interoperation

Genomics, systems biology and drug development for infectious diseases.

PubMed

Sakata, Tomoyo; Winzeler, Elizabeth A

2007-12-01

Although a variety of drugs are available for many infectious diseases that predominantly affect the developing world reasons remain for continuing to search for new chemotherapeutics. First, the development of microbial resistance has made some of the most effective and inexpensive drug regimes unreliable and dangerous to use on severely ill patients. Second, many existing antimicrobial drugs show toxicity or are too expensive for countries where the per capita income is in the order of hundreds of dollars per year. In recognition of this, new publicly and privately financed drug discovery efforts have been established to identify and develop new therapies for diseases such as tuberculosis, malaria and AIDS. This in turn, has intensified the need for tools to facilitate drug identification for those microbes whose molecular biology is poorly understood, or which are difficult to grow in the laboratory. While much has been written about how functional genomics can be used to find novel protein targets for chemotherapeutics this review will concentrate on how genome-wide, systems biology approaches may be used following whole organism, cell-based screening to understand the mechanism of drug action or to identify biological targets of small molecules. Here we focus on protozoan parasites, however, many of the approaches can be applied to pathogenic bacteria or parasitic helminths, insects or disease-causing fungi.

Cloning-free template DNA preparation for cell-free protein synthesis via two-step PCR using versatile primer designs with short 3'-UTR.

PubMed

Nomoto, Mika; Tada, Yasuomi

2018-01-01

Cell-free protein synthesis (CFPS) systems largely retain the endogenous translation machinery of the host organism, making them highly applicable for proteomics analysis of diverse biological processes. However, laborious and time-consuming cloning procedures hinder progress with CFPS systems. Herein, we report the development of a rapid and efficient two-step polymerase chain reaction (PCR) method to prepare linear DNA templates for a wheat germ CFPS system. We developed a novel, effective short 3'-untranslated region (3'-UTR) sequence that facilitates translation. Application of the short 3'-UTR to two-step PCR enabled the generation of various transcription templates from the same plasmid, including fusion proteins with N- or C-terminal tags, and truncated proteins. Our method supports the cloning-free expression of target proteins using an mRNA pool from biological material. The established system is a highly versatile platform for in vitro protein synthesis using wheat germ CFPS. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

NASA Astrophysics Data System (ADS)

Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

2013-05-01

Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

Biological conversion of carbon dioxide and hydrogen into liquid fuels and industrial chemicals.

PubMed

Hawkins, Aaron S; McTernan, Patrick M; Lian, Hong; Kelly, Robert M; Adams, Michael W W

2013-06-01

Non-photosynthetic routes for biological fixation of carbon dioxide into valuable industrial chemical precursors and fuels are moving from concept to reality. The development of 'electrofuel'-producing microorganisms leverages techniques in synthetic biology, genetic and metabolic engineering, as well as systems-level multi-omic analysis, directed evolution, and in silico modeling. Electrofuel processes are being developed for a range of microorganisms and energy sources (e.g. hydrogen, formate, electricity) to produce a variety of target molecules (e.g. alcohols, terpenes, alkenes). This review examines the current landscape of electrofuel projects with a focus on hydrogen-utilizing organisms covering the biochemistry of hydrogenases and carbonic anhydrases, kinetic and energetic analyses of the known carbon fixation pathways, and the state of genetic systems for current and prospective electrofuel-producing microorganisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Metabolomics research of medicinal plants].

PubMed

Duan, Li-Xin; Dai, Yun-Tao; Sun, Chao; Chen, Shi-Lin

2016-11-01

Metabolomics is the comprehensively study of chemical processes involving small molecule metabolites. It is an important part of systems biology, and is widely applied in complex traditional Chinese medicine（TCM）system. Metabolites biosynthesized by medicinal plants are the effective basis for TCM. Metabolomics studies of medicinal plants will usher in a new period of vigorous development with the implementation of Herb Genome Program and the development of TCM synthetic biology. This manuscript introduces the recent research progresses of metabolomics technology and the main research contents of metabolomics studies for medicinal plants, including identification and quality evaluation for medicinal plants, cultivars breeding, stress resistance, metabolic pathways, metabolic network, metabolic engineering and synthetic biology researches. The integration of genomics, transcriptomics and metabolomics approaches will finally lay foundation for breeding of medicinal plants, R&D, quality and safety evaluation of innovative drug. Copyright© by the Chinese Pharmaceutical Association.

Systematic reconstruction of TRANSPATH data into Cell System Markup Language

PubMed Central

Nagasaki, Masao; Saito, Ayumu; Li, Chen; Jeong, Euna; Miyano, Satoru

2008-01-01

Background Many biological repositories store information based on experimental study of the biological processes within a cell, such as protein-protein interactions, metabolic pathways, signal transduction pathways, or regulations of transcription factors and miRNA. Unfortunately, it is difficult to directly use such information when generating simulation-based models. Thus, modeling rules for encoding biological knowledge into system-dynamics-oriented standardized formats would be very useful for fully understanding cellular dynamics at the system level. Results We selected the TRANSPATH database, a manually curated high-quality pathway database, which provides a plentiful source of cellular events in humans, mice, and rats, collected from over 31,500 publications. In this work, we have developed 16 modeling rules based on hybrid functional Petri net with extension (HFPNe), which is suitable for graphical representing and simulating biological processes. In the modeling rules, each Petri net element is incorporated with Cell System Ontology to enable semantic interoperability of models. As a formal ontology for biological pathway modeling with dynamics, CSO also defines biological terminology and corresponding icons. By combining HFPNe with the CSO features, it is possible to make TRANSPATH data to simulation-based and semantically valid models. The results are encoded into a biological pathway format, Cell System Markup Language (CSML), which eases the exchange and integration of biological data and models. Conclusion By using the 16 modeling rules, 97% of the reactions in TRANSPATH are converted into simulation-based models represented in CSML. This reconstruction demonstrates that it is possible to use our rules to generate quantitative models from static pathway descriptions. PMID:18570683

Systematic reconstruction of TRANSPATH data into cell system markup language.

PubMed

Nagasaki, Masao; Saito, Ayumu; Li, Chen; Jeong, Euna; Miyano, Satoru

2008-06-23

Many biological repositories store information based on experimental study of the biological processes within a cell, such as protein-protein interactions, metabolic pathways, signal transduction pathways, or regulations of transcription factors and miRNA. Unfortunately, it is difficult to directly use such information when generating simulation-based models. Thus, modeling rules for encoding biological knowledge into system-dynamics-oriented standardized formats would be very useful for fully understanding cellular dynamics at the system level. We selected the TRANSPATH database, a manually curated high-quality pathway database, which provides a plentiful source of cellular events in humans, mice, and rats, collected from over 31,500 publications. In this work, we have developed 16 modeling rules based on hybrid functional Petri net with extension (HFPNe), which is suitable for graphical representing and simulating biological processes. In the modeling rules, each Petri net element is incorporated with Cell System Ontology to enable semantic interoperability of models. As a formal ontology for biological pathway modeling with dynamics, CSO also defines biological terminology and corresponding icons. By combining HFPNe with the CSO features, it is possible to make TRANSPATH data to simulation-based and semantically valid models. The results are encoded into a biological pathway format, Cell System Markup Language (CSML), which eases the exchange and integration of biological data and models. By using the 16 modeling rules, 97% of the reactions in TRANSPATH are converted into simulation-based models represented in CSML. This reconstruction demonstrates that it is possible to use our rules to generate quantitative models from static pathway descriptions.

An overview of bioinformatics methods for modeling biological pathways in yeast.

PubMed

Hou, Jie; Acharya, Lipi; Zhu, Dongxiao; Cheng, Jianlin

2016-03-01

The advent of high-throughput genomics techniques, along with the completion of genome sequencing projects, identification of protein-protein interactions and reconstruction of genome-scale pathways, has accelerated the development of systems biology research in the yeast organism Saccharomyces cerevisiae In particular, discovery of biological pathways in yeast has become an important forefront in systems biology, which aims to understand the interactions among molecules within a cell leading to certain cellular processes in response to a specific environment. While the existing theoretical and experimental approaches enable the investigation of well-known pathways involved in metabolism, gene regulation and signal transduction, bioinformatics methods offer new insights into computational modeling of biological pathways. A wide range of computational approaches has been proposed in the past for reconstructing biological pathways from high-throughput datasets. Here we review selected bioinformatics approaches for modeling biological pathways inS. cerevisiae, including metabolic pathways, gene-regulatory pathways and signaling pathways. We start with reviewing the research on biological pathways followed by discussing key biological databases. In addition, several representative computational approaches for modeling biological pathways in yeast are discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Temporal Code-Driven Stimulation: Definition and Application to Electric Fish Signaling

PubMed Central

Lareo, Angel; Forlim, Caroline G.; Pinto, Reynaldo D.; Varona, Pablo; Rodriguez, Francisco de Borja

2016-01-01

Closed-loop activity-dependent stimulation is a powerful methodology to assess information processing in biological systems. In this context, the development of novel protocols, their implementation in bioinformatics toolboxes and their application to different description levels open up a wide range of possibilities in the study of biological systems. We developed a methodology for studying biological signals representing them as temporal sequences of binary events. A specific sequence of these events (code) is chosen to deliver a predefined stimulation in a closed-loop manner. The response to this code-driven stimulation can be used to characterize the system. This methodology was implemented in a real time toolbox and tested in the context of electric fish signaling. We show that while there are codes that evoke a response that cannot be distinguished from a control recording without stimulation, other codes evoke a characteristic distinct response. We also compare the code-driven response to open-loop stimulation. The discussed experiments validate the proposed methodology and the software toolbox. PMID:27766078

Temporal Code-Driven Stimulation: Definition and Application to Electric Fish Signaling.

PubMed

Lareo, Angel; Forlim, Caroline G; Pinto, Reynaldo D; Varona, Pablo; Rodriguez, Francisco de Borja

2016-01-01

Closed-loop activity-dependent stimulation is a powerful methodology to assess information processing in biological systems. In this context, the development of novel protocols, their implementation in bioinformatics toolboxes and their application to different description levels open up a wide range of possibilities in the study of biological systems. We developed a methodology for studying biological signals representing them as temporal sequences of binary events. A specific sequence of these events (code) is chosen to deliver a predefined stimulation in a closed-loop manner. The response to this code-driven stimulation can be used to characterize the system. This methodology was implemented in a real time toolbox and tested in the context of electric fish signaling. We show that while there are codes that evoke a response that cannot be distinguished from a control recording without stimulation, other codes evoke a characteristic distinct response. We also compare the code-driven response to open-loop stimulation. The discussed experiments validate the proposed methodology and the software toolbox.

Fundamental Biological Research on the International Space Station

NASA Technical Reports Server (NTRS)

Souza, K. A.; Yost, Bruce; Fletcher, L.; Dalton, Bonnie P. (Technical Monitor)

2000-01-01

The fundamental Biology Program of NASA's Life Sciences Division is chartered with enabling and sponsoring research on the International Space Station (ISS) in order to understand the effects of the space flight environment, particularly microgravity, on living systems. To accomplish this goal, NASA Ames Research Center (ARC) has been tasked with managing the development of a number of biological habitats, along with their support systems infrastructure. This integrated suite of habitats and support systems is being designed to support research requirements identified by the scientific community. As such, it will support investigations using cells and tissues, avian eggs, insects, plants, aquatic organisms and rodents. Studies following organisms through complete life cycles and over multiple generations will eventually be possible. As an adjunct to the development of these basic habitats, specific analytical and monitoring technologies are being targeted for maturation to complete the research cycle by transferring existing or emerging analytical techniques, sensors, and processes from the laboratory bench to the ISS research platform.

Oligodendroglia: metabolic supporters of axons.

PubMed

Morrison, Brett M; Lee, Youngjin; Rothstein, Jeffrey D

2013-12-01

Axons are specialized extensions of neurons that are critical for the organization of the nervous system. To maintain function in axons that often extend some distance from the cell body, specialized mechanisms of energy delivery are likely to be necessary. Over the past decade, greater understanding of human demyelinating diseases and the development of animal models have suggested that oligodendroglia are critical for maintaining the function of axons. In this review, we discuss evidence for the vulnerability of neurons to energy deprivation, the importance of oligodendrocytes for axon function and survival, and recent data suggesting that transfer of energy metabolites from oligodendroglia to axons through monocarboxylate transporter 1 (MCT1) may be critical for the survival of axons. This pathway has important implications both for the basic biology of the nervous system and for human neurological disease. New insights into the role of oligodendroglial biology provide an exciting opportunity for revisions in nervous system biology, understanding myelin-based disorders, and therapeutics development. Copyright © 2013 Elsevier Ltd. All rights reserved.

Computational Systems Biology

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDermott, Jason E.; Samudrala, Ram; Bumgarner, Roger E.

2009-05-01

Computational systems biology is the term that we use to describe computational methods to identify, infer, model, and store relationships between the molecules, pathways, and cells (“systems”) involved in a living organism. Based on this definition, the field of computational systems biology has been in existence for some time. However, the recent confluence of high throughput methodology for biological data gathering, genome-scale sequencing and computational processing power has driven a reinvention and expansion of this field. The expansions include not only modeling of small metabolic{Ishii, 2004 #1129; Ekins, 2006 #1601; Lafaye, 2005 #1744} and signaling systems{Stevenson-Paulik, 2006 #1742; Lafaye, 2005more » #1744} but also modeling of the relationships between biological components in very large systems, incluyding whole cells and organisms {Ideker, 2001 #1124; Pe'er, 2001 #1172; Pilpel, 2001 #393; Ideker, 2002 #327; Kelley, 2003 #1117; Shannon, 2003 #1116; Ideker, 2004 #1111}{Schadt, 2003 #475; Schadt, 2006 #1661}{McDermott, 2002 #878; McDermott, 2005 #1271}. Generally these models provide a general overview of one or more aspects of these systems and leave the determination of details to experimentalists focused on smaller subsystems. The promise of such approaches is that they will elucidate patterns, relationships and general features that are not evident from examining specific components or subsystems. These predictions are either interesting in and of themselves (for example, the identification of an evolutionary pattern), or are interesting and valuable to researchers working on a particular problem (for example highlight a previously unknown functional pathway). Two events have occurred to bring about the field computational systems biology to the forefront. One is the advent of high throughput methods that have generated large amounts of information about particular systems in the form of genetic studies, gene expression analyses (both protein and mRNA) and metabolomics. With such tools, research to consider systems as a whole are being conceived, planned and implemented experimentally on an ever more frequent and wider scale. The other is the growth of computational processing power and tools. Methods to analyze large data sets of this kind are often computationally demanding and, as is the case in other areas, the field has benefited from continuing improvements in computational hardware and methods. The field of computational biology is very much like a telescope with two sequential lenses: one lens represents the biological data and the other represents a computational and/or mathematical model of the data. Both lenses must be properly coordinated to yield an image that reflects biological reality. This means that the design parameters for both lenses must be designed in concert to create a system that yields a model of the organism that provides both predictive and mechanistic information. The chapters in this book describe the construction of subcomponents of such a system. Computational systems biology is a rapidly evolving field and no single group of investigators has yet developed a compete system that integrates both data generation and data analysis in such a way so as to allow full and accurate modeling of any single biological organism. However, the field is rapidly moving in that direction. The chapters in this book represent a snapshot of the current methods being developed and used in the area of computational systems biology. Each method or database described within represents one or more steps on the path to a complete description of a biological system. How these tools will evolve and ultimately be integrated is an area of intense research and interest. We hope that readers of this book will be motivated by the chapters within and become involved in this exciting area of research.« less

Root Systems Biology: Integrative Modeling across Scales, from Gene Regulatory Networks to the Rhizosphere1

PubMed Central

Hill, Kristine; Porco, Silvana; Lobet, Guillaume; Zappala, Susan; Mooney, Sacha; Draye, Xavier; Bennett, Malcolm J.

2013-01-01

Genetic and genomic approaches in model organisms have advanced our understanding of root biology over the last decade. Recently, however, systems biology and modeling have emerged as important approaches, as our understanding of root regulatory pathways has become more complex and interpreting pathway outputs has become less intuitive. To relate root genotype to phenotype, we must move beyond the examination of interactions at the genetic network scale and employ multiscale modeling approaches to predict emergent properties at the tissue, organ, organism, and rhizosphere scales. Understanding the underlying biological mechanisms and the complex interplay between systems at these different scales requires an integrative approach. Here, we describe examples of such approaches and discuss the merits of developing models to span multiple scales, from network to population levels, and to address dynamic interactions between plants and their environment. PMID:24143806

Dynamics of problem setting and framing in citizen discussions on synthetic biology

PubMed Central

Betten, Afke Wieke; Broerse, Jacqueline E.W.; Kupper, Frank

2017-01-01

Synthetic biology is an emerging scientific field where engineers and biologists design and build biological systems for various applications. Developing synthetic biology responsibly in the public interest necessitates a meaningful societal dialogue. In this article, we argue that facilitating such a dialogue requires an understanding of how people make sense of synthetic biology. We performed qualitative research to unravel the underlying dynamics of problem setting and framing in citizen discussions on synthetic biology. We found that most people are not inherently for or against synthetic biology as a technology or development in itself, but that their perspectives are framed by core values about our relationships with science and technology and that sensemaking is much dependent on the context and general feelings of (dis)content. Given that there are many assumptions focused on a more binary idea of the public’s view, we emphasize the need for frame awareness and understanding in a meaningful dialogue. PMID:28597721

[Application of microelectronics CAD tools to synthetic biology].

PubMed

Madec, Morgan; Haiech, Jacques; Rosati, Élise; Rezgui, Abir; Gendrault, Yves; Lallement, Christophe

2017-02-01

Synthetic biology is an emerging science that aims to create new biological functions that do not exist in nature, based on the knowledge acquired in life science over the last century. Since the beginning of this century, several projects in synthetic biology have emerged. The complexity of the developed artificial bio-functions is relatively low so that empirical design methods could be used for the design process. Nevertheless, with the increasing complexity of biological circuits, this is no longer the case and a large number of computer aided design softwares have been developed in the past few years. These tools include languages for the behavioral description and the mathematical modelling of biological systems, simulators at different levels of abstraction, libraries of biological devices and circuit design automation algorithms. All of these tools already exist in other fields of engineering sciences, particularly in microelectronics. This is the approach that is put forward in this paper. © 2017 médecine/sciences – Inserm.

Holistic systems biology approaches to molecular mechanisms of human helper T cell differentiation to functionally distinct subsets.

PubMed

Chen, Z; Lönnberg, T; Lahesmaa, R

2013-08-01

Current knowledge of helper T cell differentiation largely relies on data generated from mouse studies. To develop therapeutical strategies combating human diseases, understanding the molecular mechanisms how human naïve T cells differentiate to functionally distinct T helper (Th) subsets as well as studies on human differentiated Th cell subsets is particularly valuable. Systems biology approaches provide a holistic view of the processes of T helper differentiation, enable discovery of new factors and pathways involved and generation of new hypotheses to be tested to improve our understanding of human Th cell differentiation and immune-mediated diseases. Here, we summarize studies where high-throughput systems biology approaches have been exploited to human primary T cells. These studies reveal new factors and signalling pathways influencing T cell differentiation towards distinct subsets, important for immune regulation. Such information provides new insights into T cell biology and into targeting immune system for therapeutic interventions. © 2013 John Wiley & Sons Ltd.

A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aderem, Alan; Adkins, Joshua N.; Ansong, Charles

The 20th century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and water borne illnesses are frequent, multi-drug resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the 21st century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondinglymore » deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program we think that the time is at hand to redefine the pathogen-host research paradigm.« less

A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

PubMed Central

Aderem, Alan; Adkins, Joshua N.; Ansong, Charles; Galagan, James; Kaiser, Shari; Korth, Marcus J.; Law, G. Lynn; McDermott, Jason G.; Proll, Sean C.; Rosenberger, Carrie; Schoolnik, Gary; Katze, Michael G.

2011-01-01

The twentieth century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and waterborne illnesses are frequent, multidrug-resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the twenty-first century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program, we think that the time is at hand to redefine the pathogen-host research paradigm. PMID:21285433

Set membership experimental design for biological systems.

PubMed

Marvel, Skylar W; Williams, Cranos M

2012-03-21

Experimental design approaches for biological systems are needed to help conserve the limited resources that are allocated for performing experiments. The assumptions used when assigning probability density functions to characterize uncertainty in biological systems are unwarranted when only a small number of measurements can be obtained. In these situations, the uncertainty in biological systems is more appropriately characterized in a bounded-error context. Additionally, effort must be made to improve the connection between modelers and experimentalists by relating design metrics to biologically relevant information. Bounded-error experimental design approaches that can assess the impact of additional measurements on model uncertainty are needed to identify the most appropriate balance between the collection of data and the availability of resources. In this work we develop a bounded-error experimental design framework for nonlinear continuous-time systems when few data measurements are available. This approach leverages many of the recent advances in bounded-error parameter and state estimation methods that use interval analysis to generate parameter sets and state bounds consistent with uncertain data measurements. We devise a novel approach using set-based uncertainty propagation to estimate measurement ranges at candidate time points. We then use these estimated measurements at the candidate time points to evaluate which candidate measurements furthest reduce model uncertainty. A method for quickly combining multiple candidate time points is presented and allows for determining the effect of adding multiple measurements. Biologically relevant metrics are developed and used to predict when new data measurements should be acquired, which system components should be measured and how many additional measurements should be obtained. The practicability of our approach is illustrated with a case study. This study shows that our approach is able to 1) identify candidate measurement time points that maximize information corresponding to biologically relevant metrics and 2) determine the number at which additional measurements begin to provide insignificant information. This framework can be used to balance the availability of resources with the addition of one or more measurement time points to improve the predictability of resulting models.

Set membership experimental design for biological systems

PubMed Central

2012-01-01

Background Experimental design approaches for biological systems are needed to help conserve the limited resources that are allocated for performing experiments. The assumptions used when assigning probability density functions to characterize uncertainty in biological systems are unwarranted when only a small number of measurements can be obtained. In these situations, the uncertainty in biological systems is more appropriately characterized in a bounded-error context. Additionally, effort must be made to improve the connection between modelers and experimentalists by relating design metrics to biologically relevant information. Bounded-error experimental design approaches that can assess the impact of additional measurements on model uncertainty are needed to identify the most appropriate balance between the collection of data and the availability of resources. Results In this work we develop a bounded-error experimental design framework for nonlinear continuous-time systems when few data measurements are available. This approach leverages many of the recent advances in bounded-error parameter and state estimation methods that use interval analysis to generate parameter sets and state bounds consistent with uncertain data measurements. We devise a novel approach using set-based uncertainty propagation to estimate measurement ranges at candidate time points. We then use these estimated measurements at the candidate time points to evaluate which candidate measurements furthest reduce model uncertainty. A method for quickly combining multiple candidate time points is presented and allows for determining the effect of adding multiple measurements. Biologically relevant metrics are developed and used to predict when new data measurements should be acquired, which system components should be measured and how many additional measurements should be obtained. Conclusions The practicability of our approach is illustrated with a case study. This study shows that our approach is able to 1) identify candidate measurement time points that maximize information corresponding to biologically relevant metrics and 2) determine the number at which additional measurements begin to provide insignificant information. This framework can be used to balance the availability of resources with the addition of one or more measurement time points to improve the predictability of resulting models. PMID:22436240

Monitoring osseointegration and developing intelligent systems (Conference Presentation)

NASA Astrophysics Data System (ADS)

Salvino, Liming W.

2017-05-01

Effective monitoring of structural and biological systems is an extremely important research area that enables technology development for future intelligent devices, platforms, and systems. This presentation provides an overview of research efforts funded by the Office of Naval Research (ONR) to establish structural health monitoring (SHM) methodologies in the human domain. Basic science efforts are needed to utilize SHM sensing, data analysis, modeling, and algorithms to obtain the relevant physiological and biological information for human-specific health and performance conditions. This overview of current research efforts is based on the Monitoring Osseointegrated Prosthesis (MOIP) program. MOIP develops implantable and intelligent prosthetics that are directly anchored to the bone of residual limbs. Through real-time monitoring, sensing, and responding to osseointegration of bones and implants as well as interface conditions and environment, our research program aims to obtain individualized actionable information for implant failure identification, load estimation, infection mitigation and treatment, as well as healing assessment. Looking ahead to achieve ultimate goals of SHM, we seek to expand our research areas to cover monitoring human, biological and engineered systems, as well as human-machine interfaces. Examples of such include 1) brainwave monitoring and neurological control, 2) detecting and evaluating brain injuries, 3) monitoring and maximizing human-technological object teaming, and 4) closed-loop setups in which actions can be triggered automatically based on sensors, actuators, and data signatures. Finally, some ongoing and future collaborations across different disciplines for the development of knowledge automation and intelligent systems will be discussed.

Geospatial Technology Applications and Infrastructure in the Biological Resources Division

USGS Publications Warehouse

D'Erchia, Frank; Getter, James; D'Erchia, Terry D.; Root, Ralph; Stitt, Susan; White, Barbara

1998-01-01

Executive Summary -- Automated spatial processing technology such as geographic information systems (GIS), telemetry, and satellite-based remote sensing are some of the more recent developments in the long history of geographic inquiry. For millennia, humankind has endeavored to map the Earth's surface and identify spatial relationships. But the precision with which we can locate geographic features has increased exponentially with satellite positioning systems. Remote sensing, GIS, thematic mapping, telemetry, and satellite positioning systems such as the Global Positioning System (GPS) are tools that greatly enhance the quality and rapidity of analysis of biological resources. These technologies allow researchers, planners, and managers to more quickly and accurately determine appropriate strategies and actions. Researchers and managers can view information from new and varying perspectives using GIS and remote sensing, and GPS receivers allow the researcher or manager to identify the exact location of interest. These geospatial technologies support the mission of the U.S. Geological Survey (USGS) Biological Resources Division (BRD) and the Strategic Science Plan (BRD 1996) by providing a cost-effective and efficient method for collection, analysis, and display of information. The BRD mission is 'to work with others to provide the scientific understanding and technologies needed to support the sound management and conservation of our Nation's biological resources.' A major responsibility of the BRD is to develop and employ advanced technologies needed to synthesize, analyze, and disseminate biological and ecological information. As the Strategic Science Plan (BRD 1996) states, 'fulfilling this mission depends on effectively balancing the immediate need for information to guide management of biological resources with the need for technical assistance and long-range, strategic information to understand and predict emerging patterns and trends in ecological systems.' Information sharing plays a key role in nearly everything BRD does. The Strategic Science Plan discusses the need to (1) develop tools and standards for information transfer, (2) disseminate information, and (3) facilitate effective use of information. This effort centers around the National Biological Information Infrastructure (NBII) and the National Spatial Data Infrastructure (NSDI), components of the National Information Infrastructure. The NBII and NSDI are distributed electronic networks of biological and geographical data and information, as well as tools to help users around the world easily find and retrieve the biological and geographical data and information they need. The BRD is responsible for developing scientifically and statistically reliable methods and protocols to assess the status and trends of the Nation's biological resources. Scientists also conduct important inventory and monitoring studies to maintain baseline information on these same resources. Research on those species for which the Department of the Interior (DOI) has trust responsibilities (including endangered species and migratory species) involves laboratory and field studies of individual animals and the environments in which they live. Researchboth tactical and strategicis conducted at the BRD's 17 science centers and 81 field stations, 54 Cooperative Fish and Wildlife Research Units in 40 states, and at 11 former Cooperative Park Study Units. Studies encompass fish, birds, mammals, and plants, as well as their ecosystems and the surrounding landscape. Biological Resources Division researchers use a variety of scientific tools in their endeavors to understand the causes of biological and ecological trends. Research results are used by managers to predict environmental changes and to help them take appropriate measures to manage resources effectively. The BRD Geospatial Technology Program facilitates the collection, analysis, and dissemination of data and informat

From immunology to MRI data anlysis: Problems in mathematical biology

NASA Astrophysics Data System (ADS)

Waters, Ryan Samuel

This thesis represents a collection of four distinct biological projects rising from immunology and metabolomics that required unique and creative mathematical approaches. One project focuses on understanding the role IL-2 plays in immune response regulation and exploring how these effects can be altered. We developed several dynamic models of the receptor signaling network which we analyze analytically and numerically. In a second project focused also on MS, we sought to create a system for grading magnetic resonance images (MRI) with good correlation with disability. The goal is for these MRI scores to provide a better standard for large-scale clinical drug trials, which limits the bias associated with differences in available MRI technology and general grader/participant variability. The third project involves the study of the CRISPR adaptive immune system in bacteria. Bacterial cells recognize and acquire snippets of exogenous genetic material, which they incorporate into their DNA. In this project we explore the optimal design for the CRISPR system given a viral distribution to maximize its probability of survival. The final project involves the study of the benefits for colocalization of coupled enzymes in metabolic pathways. The hypothesized kinetic advantage, known as `channeling', of putting coupled enzymes closer together has been used as justification for the colocalization of coupled enzymes in biological systems. We developed and analyzed a simple partial differential equation of the diffusion of the intermediate substrate between coupled enzymes to explore the phenomena of channeling. The four projects of my thesis represent very distinct biological problems that required a variety of techniques from diverse areas of mathematics ranging from dynamical modeling to statistics, Fourier series and calculus of variations. In each case, quantitative techniques were used to address biological questions from a mathematical perspective ultimately providing insight back to the biological problems which motivated them.

Improving Collaboration by Standardization Efforts in Systems Biology

PubMed Central

Dräger, Andreas; Palsson, Bernhard Ø.

2014-01-01

Collaborative genome-scale reconstruction endeavors of metabolic networks would not be possible without a common, standardized formal representation of these systems. The ability to precisely define biological building blocks together with their dynamic behavior has even been considered a prerequisite for upcoming synthetic biology approaches. Driven by the requirements of such ambitious research goals, standardization itself has become an active field of research on nearly all levels of granularity in biology. In addition to the originally envisaged exchange of computational models and tool interoperability, new standards have been suggested for an unambiguous graphical display of biological phenomena, to annotate, archive, as well as to rank models, and to describe execution and the outcomes of simulation experiments. The spectrum now even covers the interaction of entire neurons in the brain, three-dimensional motions, and the description of pharmacometric studies. Thereby, the mathematical description of systems and approaches for their (repeated) simulation are clearly separated from each other and also from their graphical representation. Minimum information definitions constitute guidelines and common operation protocols in order to ensure reproducibility of findings and a unified knowledge representation. Central database infrastructures have been established that provide the scientific community with persistent links from model annotations to online resources. A rich variety of open-source software tools thrives for all data formats, often supporting a multitude of programing languages. Regular meetings and workshops of developers and users lead to continuous improvement and ongoing development of these standardization efforts. This article gives a brief overview about the current state of the growing number of operation protocols, mark-up languages, graphical descriptions, and fundamental software support with relevance to systems biology. PMID:25538939

Space Synthetic Biology Project

NASA Technical Reports Server (NTRS)

Howard, David; Roman, Monsi; Mansell, James (Matt)

2015-01-01

Synthetic biology is an effort to make genetic engineering more useful by standardizing sections of genetic code. By standardizing genetic components, biological engineering will become much more similar to traditional fields of engineering, in which well-defined components and subsystems are readily available in markets. Specifications of the behavior of those components and subsystems can be used to model a system which incorporates them. Then, the behavior of the novel system can be simulated and optimized. Finally, the components and subsystems can be purchased and assembled to create the optimized system, which most often will exhibit behavior similar to that indicated by the model. The Space Synthetic Biology project began in 2012 as a multi-Center effort. The purpose of this project was to harness Synthetic Biology principals to enable NASA's missions. A central target for application was to Environmental Control & Life Support (ECLS). Engineers from NASA Marshall Space Flight Center's (MSFC's) ECLS Systems Development Branch (ES62) were brought into the project to contribute expertise in operational ECLS systems. Project lead scientists chose to pursue the development of bioelectrochemical technologies to spacecraft life support. Therefore, the ECLS element of the project became essentially an effort to develop a bioelectrochemical ECLS subsystem. Bioelectrochemical systems exploit the ability of many microorganisms to drive their metabolisms by direct or indirect utilization of electrical potential gradients. Whereas many microorganisms are capable of deriving the energy required for the processes of interest (such as carbon dioxide (CO2) fixation) from sunlight, it is believed that subsystems utilizing electrotrophs will exhibit smaller mass, volume, and power requirements than those that derive their energy from sunlight. In the first 2 years of the project, MSFC personnel conducted modeling, simulation, and conceptual design efforts to assist the project in selecting the best approaches to the application of bioelectrochemical technologies to ECLS. Figure 1 shows results of simulation of charge transport in an experimental system. Figure 2 shows one of five conceptual designs for ECLS subsystems based on bioelectrochemical reactors. Also during the first 2 years, some work was undertaken to gather fundamental data (conductivities, overpotentials) relevant to the modeling efforts.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogura, Toshihiko, E-mail: t-ogura@aist.go.jp

Highlights: • We developed a high-sensitive frequency transmission electric-field (FTE) system. • The output signal was highly enhanced by applying voltage to a metal layer on SiN. • The spatial resolution of new FTE method is 41 nm. • New FTE system enables observation of the intact bacteria and virus in water. - Abstract: The high-resolution structural analysis of biological specimens by scanning electron microscopy (SEM) presents several advantages. Until now, wet bacterial specimens have been examined using atmospheric sample holders. However, images of unstained specimens in water using these holders exhibit very poor contrast and heavy radiation damage. Recently,more » we developed the frequency transmission electric-field (FTE) method, which facilitates the SEM observation of biological specimens in water without radiation damage. However, the signal detection system presents low sensitivity. Therefore, a high EB current is required to generate clear images, and thus reducing spatial resolution and inducing thermal damage to the samples. Here a high-sensitivity detection system is developed for the FTE method, which enhances the output signal amplitude by hundredfold. The detection signal was highly enhanced when voltage was applied to the metal layer on silicon nitride thin film. This enhancement reduced the EB current and improved the spatial resolution as well as the signal-to-noise ratio. The spatial resolution of a high-sensitive FTE system is 41 nm, which is considerably higher than previous FTE system. New FTE system can easily be utilised to examine various unstained biological specimens in water, such as living bacteria and viruses.« less

In search of mitochondrial mechanisms: interfield excursions between cell biology and biochemistry.

PubMed

Bechtel, William; Abrahamsen, Adele

2007-01-01

Developing models of biological mechanisms, such as those involved in respiration in cells, often requires collaborative effort drawing upon techniques developed and information generated in different disciplines. Biochemists in the early decades of the 20th century uncovered all but the most elusive chemical operations involved in cellular respiration, but were unable to align the reaction pathways with particular structures in the cell. During the period 1940-1965 cell biology was emerging as a new discipline and made distinctive contributions to understanding the role of the mitochondrion and its component parts in cellular respiration. In particular, by developing techniques for localizing enzymes or enzyme systems in specific cellular components, cell biologists provided crucial information about the organized structures in which the biochemical reactions occurred. Although the idea that biochemical operations are intimately related to and depend on cell structures was at odds with the then-dominant emphasis on systems of soluble enzymes in biochemistry, a reconceptualization of energetic processes in the 1960s and 1970s made it clear why cell structure was critical to the biochemical account. This paper examines how numerous excursions between biochemistry and cell biology contributed a new understanding of the mechanism of cellular respiration.

The Unicellular State as a Point Source in a Quantum Biological System

PubMed Central

Torday, John S.; Miller, William B.

2016-01-01

A point source is the central and most important point or place for any group of cohering phenomena. Evolutionary development presumes that biological processes are sequentially linked, but neither directed from, nor centralized within, any specific biologic structure or stage. However, such an epigenomic entity exists and its transforming effects can be understood through the obligatory recapitulation of all eukaryotic lifeforms through a zygotic unicellular phase. This requisite biological conjunction can now be properly assessed as the focal point of reconciliation between biology and quantum phenomena, illustrated by deconvoluting complex physiologic traits back to their unicellular origins. PMID:27240413

Next-Gen Gene Synthesis Enables Large-Scale Engineering in Biological Systems: Recent advances in synthetic biology are making this field more promising than ever.

PubMed

Leake, Devin

2015-01-01

As scientists make strides toward the goal of developing a form of biological engineering that's as predictive and reliable as chemical engineering is for chemistry, one technology component has become absolutely critical: gene synthesis. Gene synthesis is the process of building stretches of deoxyribonucleic acid (DNA) to order--some stretches based on DNA that exists already in nature, some based on novel designs intended to accomplish new functions. This process is the foundation of synthetic biology, which is rapidly becoming the engineering counterpart to biology.