Tracking the emergence of synthetic biology.

PubMed

Shapira, Philip; Kwon, Seokbeom; Youtie, Jan

2017-01-01

Synthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research, innovation, and policy interest in recent years. This paper contributes to efforts to delineate this emerging domain by presenting a newly constructed bibliometric definition of synthetic biology. Our approach is dimensioned from a core set of papers in synthetic biology, using procedures to obtain benchmark synthetic biology publication records, extract keywords from these benchmark records, and refine the keywords, supplemented with articles published in dedicated synthetic biology journals. We compare our search strategy with other recent bibliometric approaches to define synthetic biology, using a common source of publication data for the period from 2000 to 2015. The paper details the rapid growth and international spread of research in synthetic biology in recent years, demonstrates that diverse research disciplines are contributing to the multidisciplinary development of synthetic biology research, and visualizes this by profiling synthetic biology research on the map of science. We further show the roles of a relatively concentrated set of research sponsors in funding the growth and trajectories of synthetic biology. In addition to discussing these analyses, the paper notes limitations and suggests lines for further work.

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.

Plant synthetic biology.

PubMed

Liu, Wusheng; Stewart, C Neal

2015-05-01

Plant synthetic biology is an emerging field that combines engineering principles with plant biology toward the design and production of new devices. This emerging field should play an important role in future agriculture for traditional crop improvement, but also in enabling novel bioproduction in plants. In this review we discuss the design cycles of synthetic biology as well as key engineering principles, genetic parts, and computational tools that can be utilized in plant synthetic biology. Some pioneering examples are offered as a demonstration of how synthetic biology can be used to modify plants for specific purposes. These include synthetic sensors, synthetic metabolic pathways, and synthetic genomes. We also speculate about the future of synthetic biology of plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

3rd congress on applied synthetic biology in Europe (Costa da Caparica, Portugal, February 2016).

PubMed

Cueva, Miguel

2017-03-25

The third meeting organised by the European Federation of Biotechnology (EFB) on advances in Applied Synthetic Biotechnology in Europe (ASBE) was held in Costa da Caparica, Portugal, in February 2016. Abundant novel applications in synthetic biology were described in the six sessions of the meeting, which was divided into technology and tools for synthetic biology (I, II and III), bionanoscience, biosynthetic pathways and enzyme synthetic biology, and metabolic engineering and chemical manufacturing. The meeting presented numerous methods for the development of novel synthetic strains, synthetic biological tools and synthetic biology applications. With the aid of synthetic biology, production costs of chemicals, metabolites and food products are expected to decrease, by generating sustainable biochemical production of such resources. Also, such synthetic biological advances could be applied for medical purposes, as in pharmaceuticals and for biosensors. Recurrent, linked themes throughout the meeting were the shortage of resources, the world's transition into a bioeconomy, and how synthetic biology is helping tackle these issues through cutting-edge technologies. While there are still limitations in synthetic biology research, innovation is propelling the development of technology, the standardisation of synthetic biological tools and the use of suitable host organisms. These developments are laying a foundation to providing a future where cutting-edge research could generate potential solutions to society's pressing issues, thus incentivising a transition into a bioeconomy. Copyright © 2016 Elsevier B.V. All rights reserved.

A living foundry for Synthetic Biological Materials: A synthetic biology roadmap to new advanced materials.

PubMed

Le Feuvre, Rosalind A; Scrutton, Nigel S

2018-06-01

Society is on the cusp of harnessing recent advances in synthetic biology to discover new bio-based products and routes to their affordable and sustainable manufacture. This is no more evident than in the discovery and manufacture of Synthetic Biological Materials , where synthetic biology has the capacity to usher in a new Materials from Biology era that will revolutionise the discovery and manufacture of innovative synthetic biological materials. These will encompass novel, smart, functionalised and hybrid materials for diverse applications whose discovery and routes to bio-production will be stimulated by the fusion of new technologies positioned across physical, digital and biological spheres. This article, which developed from an international workshop held in Manchester, United Kingdom, in 2017 [1], sets out to identify opportunities in the new materials from biology era. It considers requirements, early understanding and foresight of the challenges faced in delivering a Discovery to Manufacturing Pipeline for synthetic biological materials using synthetic biology approaches. This challenge spans the complete production cycle from intelligent and predictive design, fabrication, evaluation and production of synthetic biological materials to new ways of bringing these products to market. Pathway opportunities are identified that will help foster expertise sharing and infrastructure development to accelerate the delivery of a new generation of synthetic biological materials and the leveraging of existing investments in synthetic biology and advanced materials research to achieve this goal.

Autonomy and Fear of Synthetic Biology: How Can Patients' Autonomy Be Enhanced in the Field of Synthetic Biology? A Qualitative Study with Stable Patients.

PubMed

Rakic, Milenko; Wienand, Isabelle; Shaw, David; Nast, Rebecca; Elger, Bernice S

2017-04-01

We analyzed stable patients' views regarding synthetic biology in general, the medical application of synthetic biology, and their potential participation in trials of synthetic biology in particular. The aim of the study was to find out whether patients' views and preferences change after receiving more detailed information about synthetic biology and its clinical applications. The qualitative study was carried out with a purposive sample of 36 stable patients, who suffered from diabetes or gout. Interviews were transcribed verbatim, translated and fully anonymized. Thematic analysis was applied in order to examine stable patients' attitudes towards synthetic biology, its medical application, and their participation in trials. When patients were asked about synthetic biology in general, most of them were anxious that something uncontrollable could be created. After a concrete example of possible future treatment options, patients started to see synthetic biology in a more positive way. Our study constitutes an important first empirical insight into stable patients' views on synthetic biology and into the kind of fears triggered by the term "synthetic biology." Our results show that clear and concrete information can change patients' initial negative feelings towards synthetic biology. Information should thus be transmitted with great accuracy and transparency in order to reduce irrational fears of patients and to minimize the risk that researchers present facts too positively for the purposes of persuading patients to participate in clinical trials. Potential participants need to be adequately informed in order to be able to autonomously decide whether to participate in human subject research involving synthetic biology.

Cell-free biology: exploiting the interface between synthetic biology and synthetic chemistry

PubMed Central

Harris, D. Calvin; Jewett, Michael C.

2014-01-01

Just as synthetic organic chemistry once revolutionized the ability of chemists to build molecules (including those that did not exist in nature) following a basic set of design rules, cell-free synthetic biology is beginning to provide an improved toolbox and faster process for not only harnessing but also expanding the chemistry of life. At the interface between chemistry and biology, research in cell-free synthetic systems is proceeding in two different directions: using synthetic biology for synthetic chemistry and using synthetic chemistry to reprogram or mimic biology. In the coming years, the impact of advances inspired by these approaches will make possible the synthesis of non-biological polymers having new backbone compositions, new chemical properties, new structures, and new functions. PMID:22483202

Opportunities in plant synthetic biology.

PubMed

Cook, Charis; Martin, Lisa; Bastow, Ruth

2014-05-01

Synthetic biology is an emerging field uniting scientists from all disciplines with the aim of designing or re-designing biological processes. Initially, synthetic biology breakthroughs came from microbiology, chemistry, physics, computer science, materials science, mathematics, and engineering disciplines. A transition to multicellular systems is the next logical step for synthetic biologists and plants will provide an ideal platform for this new phase of research. This meeting report highlights some of the exciting plant synthetic biology projects, and tools and resources, presented and discussed at the 2013 GARNet workshop on plant synthetic biology.

[Synthetic biology and rearrangements of microbial genetic material].

PubMed

Liang, Quan-Feng; Wang, Qian; Qi, Qing-Sheng

2011-10-01

As an emerging discipline, synthetic biology has shown great scientific values and application prospects. Although there have been many reviews of various aspects on synthetic biology over the last years, this article, for the first time, attempted to discuss the relationship and difference between microbial genetics and synthetic biology. We summarized the recent development of synthetic biology in rearranging microbial genetic materials, including synthesis, design and reduction of genetic materials, standardization of genetic parts and modularization of genetic circuits. The relationship between synthetic biology and microbial genetic engineering was also discussed in the paper.

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.

The emerging age of cell-free synthetic biology.

PubMed

Smith, Mark Thomas; Wilding, Kristen M; Hunt, Jeremy M; Bennett, Anthony M; Bundy, Bradley C

2014-08-25

The engineering of and mastery over biological parts has catalyzed the emergence of synthetic biology. This field has grown exponentially in the past decade. As increasingly more applications of synthetic biology are pursued, more challenges are encountered, such as delivering genetic material into cells and optimizing genetic circuits in vivo. An in vitro or cell-free approach to synthetic biology simplifies and avoids many of the pitfalls of in vivo synthetic biology. In this review, we describe some of the innate features that make cell-free systems compelling platforms for synthetic biology and discuss emerging improvements of cell-free technologies. We also select and highlight recent and emerging applications of cell-free synthetic biology. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Synthetic Genomics and Synthetic Biology Applications Between Hopes and Concerns

PubMed Central

König, Harald; Frank, Daniel; Heil, Reinhard; Coenen, Christopher

2013-01-01

New organisms and biological systems designed to satisfy human needs are among the aims of synthetic genomics and synthetic biology. Synthetic biology seeks to model and construct biological components, functions and organisms that do not exist in nature or to redesign existing biological systems to perform new functions. Synthetic genomics, on the other hand, encompasses technologies for the generation of chemically-synthesized whole genomes or larger parts of genomes, allowing to simultaneously engineer a myriad of changes to the genetic material of organisms. Engineering complex functions or new organisms in synthetic biology are thus progressively becoming dependent on and converging with synthetic genomics. While applications from both areas have been predicted to offer great benefits by making possible new drugs, renewable chemicals or clean energy, they have also given rise to concerns about new safety, environmental and socio-economic risks – stirring an increasingly polarizing debate. Here we intend to provide an overview on recent progress in biomedical and biotechnological applications of synthetic genomics and synthetic biology as well as on arguments and evidence related to their possible benefits, risks and governance implications. PMID:23997647

Synthetic biology, inspired by synthetic chemistry.

PubMed

Malinova, V; Nallani, M; Meier, W P; Sinner, E K

2012-07-16

The topic synthetic biology appears still as an 'empty basket to be filled'. However, there is already plenty of claims and visions, as well as convincing research strategies about the theme of synthetic biology. First of all, synthetic biology seems to be about the engineering of biology - about bottom-up and top-down approaches, compromising complexity versus stability of artificial architectures, relevant in biology. Synthetic biology accounts for heterogeneous approaches towards minimal and even artificial life, the engineering of biochemical pathways on the organismic level, the modelling of molecular processes and finally, the combination of synthetic with nature-derived materials and architectural concepts, such as a cellular membrane. Still, synthetic biology is a discipline, which embraces interdisciplinary attempts in order to have a profound, scientific base to enable the re-design of nature and to compose architectures and processes with man-made matter. We like to give an overview about the developments in the field of synthetic biology, regarding polymer-based analogs of cellular membranes and what questions can be answered by applying synthetic polymer science towards the smallest unit in life, namely a cell. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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.

Update on Bioactive Prosthetic Material for the Treatment of Hernias.

PubMed

Edelman, David S; Hodde, Jason P

2011-12-01

The use of mesh in the repair of hernias is commonplace. Synthetic mesh, like polypropylene, has been the workhorse for hernia repairs since the 1980s. Surgisis® mesh (Cook Surgical, Bloomington, IN), a biologic hernia graft material composed of purified porcine small intestinal submucosa (SIS), was first introduced to the United States in 1998 as an alternative to synthetic mesh materials. This mesh, composed of extracellular matrix collagen, fibronectin and associated glycosaminoglycans and growth factors, has been extensively investigated in animal models and used clinically in many types of surgical procedures. SIS acts as a scaffold for natural growth and strength. We reported our initial results in this publication in July 2006. Since then, there have been many more reports and numerous other bioactive prosthetic materials (BPMs) released. The object of this article is to briefly review some of the current literature on the use of BPM for inguinal hernias, sports hernias, and umbilical hernias.

Synthetic biology and occupational risk.

PubMed

Howard, John; Murashov, Vladimir; Schulte, Paul

2017-03-01

Synthetic biology is an emerging interdisciplinary field of biotechnology that involves applying the principles of engineering and chemical design to biological systems. Biosafety professionals have done an excellent job in addressing research laboratory safety as synthetic biology and gene editing have emerged from the larger field of biotechnology. Despite these efforts, risks posed by synthetic biology are of increasing concern as research procedures scale up to industrial processes in the larger bioeconomy. A greater number and variety of workers will be exposed to commercial synthetic biology risks in the future, including risks to a variety of workers from the use of lentiviral vectors as gene transfer devices. There is a need to review and enhance current protection measures in the field of synthetic biology, whether in experimental laboratories where new advances are being researched, in health care settings where treatments using viral vectors as gene delivery systems are increasingly being used, or in the industrial bioeconomy. Enhanced worker protection measures should include increased injury and illness surveillance of the synthetic biology workforce; proactive risk assessment and management of synthetic biology products; research on the relative effectiveness of extrinsic and intrinsic biocontainment methods; specific safety guidance for synthetic biology industrial processes; determination of appropriate medical mitigation measures for lentiviral vector exposure incidents; and greater awareness and involvement in synthetic biology safety by the general occupational safety and health community as well as by government occupational safety and health research and regulatory agencies.

[Application of synthetic biology to sustainable utilization of Chinese materia medica resources].

PubMed

Huang, Lu-Qi; Gao, Wei; Zhou, Yong-Jin

2014-01-01

Bioactive natural products are the material bases of Chinese materia medica resources. With successful applications of synthetic biology strategies to the researches and productions of taxol, artemisinin and tanshinone, etc, the potential ability of synthetic biology in the sustainable utilization of Chinese materia medica resources has been attracted by many researchers. This paper reviews the development of synthetic biology, the opportunities of sustainable utilization of Chinese materia medica resources, and the progress of synthetic biology applied to the researches of bioactive natural products. Furthermore, this paper also analyzes how to apply synthetic biology to sustainable utilization of Chinese materia medica resources and what the crucial factors are. Production of bioactive natural products with synthetic biology strategies will become a significant approach for the sustainable utilization of Chinese materia medica resources.

Designing synthetic biology.

PubMed

Agapakis, Christina M

2014-03-21

Synthetic biology is frequently defined as the application of engineering design principles to biology. Such principles are intended to streamline the practice of biological engineering, to shorten the time required to design, build, and test synthetic gene networks. This streamlining of iterative design cycles can facilitate the future construction of biological systems for a range of applications in the production of fuels, foods, materials, and medicines. The promise of these potential applications as well as the emphasis on design has prompted critical reflection on synthetic biology from design theorists and practicing designers from many fields, who can bring valuable perspectives to the discipline. While interdisciplinary connections between biologists and engineers have built synthetic biology via the science and the technology of biology, interdisciplinary collaboration with artists, designers, and social theorists can provide insight on the connections between technology and society. Such collaborations can open up new avenues and new principles for research and design, as well as shed new light on the challenging context-dependence-both biological and social-that face living technologies at many scales. This review is inspired by the session titled "Design and Synthetic Biology: Connecting People and Technology" at Synthetic Biology 6.0 and covers a range of literature on design practice in synthetic biology and beyond. Critical engagement with how design is used to shape the discipline opens up new possibilities for how we might design the future of synthetic biology.

75 FR 52752 - Request for Comments on Synthetic Biology

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Request for Comments on Synthetic Biology AGENCY... Bioethical Issues is requesting public comment on the emerging science of synthetic biology, including its... Commission has begun an inquiry into the emerging science of synthetic biology. The President asked the...

Synthetic biology: exploring and exploiting genetic modularity through the design of novel biological networks.

PubMed

Agapakis, Christina M; Silver, Pamela A

2009-07-01

Synthetic biology has been used to describe many biological endeavors over the past thirty years--from designing enzymes and in vitro systems, to manipulating existing metabolisms and gene expression, to creating entirely synthetic replicating life forms. What separates the current incarnation of synthetic biology from the recombinant DNA technology or metabolic engineering of the past is an emphasis on principles from engineering such as modularity, standardization, and rigorously predictive models. As such, synthetic biology represents a new paradigm for learning about and using biological molecules and data, with applications in basic science, biotechnology, and medicine. This review covers the canonical examples as well as some recent advances in synthetic biology in terms of what we know and what we can learn about the networks underlying biology, and how this endeavor may shape our understanding of living systems.

Bottom-up synthetic biology: modular design for making artificial platelets

NASA Astrophysics Data System (ADS)

Majumder, Sagardip; Liu, Allen P.

2018-01-01

Engineering artificial cells to mimic one or multiple fundamental cell biological functions is an emerging area of synthetic biology. Reconstituting functional modules from biological components in vitro is a challenging yet an important essence of bottom-up synthetic biology. Here we describe the concept of building artificial platelets using bottom-up synthetic biology and the four functional modules that together could enable such an ambitious effort.

2012 Brazilian Society of Rheumatology Consensus for the treatment of rheumatoid arthritis.

PubMed

da Mota, Licia Maria Henrique; Cruz, Boris Afonso; Brenol, Claiton Viegas; Pereira, Ivanio Alves; Rezende-Fronza, Lucila Stange; Bertolo, Manoel Barros; de Freitas, Max Victor Carioca; da Silva, Nilzio Antonio; Louzada-Júnior, Paulo; Giorgi, Rina Dalva Neubarth; Lima, Rodrigo Aires Corrêa; da Rocha Castelar Pinheiro, Geraldo

2012-01-01

To elaborate recommendations for the treatment of rheumatoid arthritis in Brazil. Literature review with articles' selection based on evidence and the expert opinion of the Rheumatoid Arthritis Committee of the Brazilian Society of Rheumatology. 1) The therapeutic decision should be shared with the patient; 2) immediately after the diagnosis, a disease-modifying antirheumatic drug (DMARD) should be prescribed, and the treatment adjusted to achieve remission; 3) treatment should be conducted by a rheumatologist; 4) the initial treatment includes synthetic DMARDs; 5) methotrexate is the drug of choice; 6) patients who fail to respond after two schedules of synthetic DMARDs should be assessed for the use of biologic DMARDs; 7) exceptionally, biologic DMARDs can be considered earlier; 8) anti-TNF agents are preferentially recommended as the initial biologic therapy; 9) after therapeutic failure of a first biologic DMARD, other biologics can be used; 10) cyclophosphamide and azathioprine can be used in severe extra-articular manifestations; 11) oral corticoid is recommended at low doses and for short periods of time; 12) non-steroidal anti-inflammatory drugs should always be prescribed in association with a DMARD; 13) clinical assessments should be performed on a monthly basis at the beginning of treatment; 14) physical therapy, rehabilitation, and occupational therapy are indicated; 15) surgical treatment is recommended to correct sequelae; 16) alternative therapy does not replace traditional therapy; 17) family planning is recommended; 18) the active search and management of comorbidities are recommended; 19) the patient's vaccination status should be recorded and updated; 20) endemic-epidemic transmissible diseases should be investigated and treated.

Chloroplast evolution, structure and functions

PubMed Central

Jensen, Poul Erik

2014-01-01

In this review, we consider a selection of recent advances in chloroplast biology. These include new findings concerning chloroplast evolution, such as the identification of Chlamydiae as a third partner in primary endosymbiosis, a second instance of primary endosymbiosis represented by the chromatophores found in amoebae of the genus Paulinella, and a new explanation for the longevity of captured chloroplasts (kleptoplasts) in sacoglossan sea slugs. The controversy surrounding the three-dimensional structure of grana, its recent resolution by tomographic analyses, and the role of the CURVATURE THYLAKOID1 (CURT1) proteins in supporting grana formation are also discussed. We also present an updated inventory of photosynthetic proteins and the factors involved in the assembly of thylakoid multiprotein complexes, and evaluate findings that reveal that cyclic electron flow involves NADPH dehydrogenase (NDH)- and PGRL1/PGR5-dependent pathways, both of which receive electrons from ferredoxin. Other topics covered in this review include new protein components of nucleoids, an updated inventory of the chloroplast proteome, new enzymes in chlorophyll biosynthesis and new candidate messengers in retrograde signaling. Finally, we discuss the first successful synthetic biology approaches that resulted in chloroplasts in which electrons from the photosynthetic light reactions are fed to enzymes derived from secondary metabolism. PMID:24991417

Synthetic biology and its regulation in the European Union.

PubMed

Buhk, Hans-Jörg

2014-12-25

The term synthetic biology is used increasingly, but without a clear definition. Most of the recent research carried out in this field is genetic engineering, as defined by current GMO-legislation in the EU. Synthetic biology has developed its own language. In vitro synthesis of DNA also carries the label synthetic biology. It is important to analyze whether present and future activities of synthetic biology are within the scope of existing EU-legislation. Copyright © 2014 Elsevier B.V. All rights reserved.

Authentic teaching and learning through synthetic biology

PubMed Central

Kuldell, Natalie

2007-01-01

Synthetic biology is an emerging engineering discipline that, if successful, will allow well-characterized biological components to be predictably and reliably built into robust organisms that achieve specific functions. Fledgling efforts to design and implement a synthetic biology curriculum for undergraduate students have shown that the co-development of this emerging discipline and its future practitioners does not undermine learning. Rather it can serve as the lynchpin of a synthetic biology curriculum. Here I describe educational goals uniquely served by synthetic biology teaching, detail ongoing curricula development efforts at MIT, and specify particular aspects of the emerging field that must develop rapidly in order to best train the next generation of synthetic biologists. PMID:18271945

Synthetic biology and metabolic engineering.

PubMed

Stephanopoulos, Gregory

2012-11-16

Metabolic engineering emerged 20 years ago as the discipline occupied with the directed modification of metabolic pathways for the microbial synthesis of various products. As such, it deals with the engineering (design, construction, and optimization) of native as well as non-natural routes of product synthesis, aided in this task by the availability of synthetic DNA, the core enabling technology of synthetic biology. The two fields, however, only partially overlap in their interest in pathway engineering. While fabrication of biobricks, synthetic cells, genetic circuits, and nonlinear cell dynamics, along with pathway engineering, have occupied researchers in the field of synthetic biology, the sum total of these areas does not constitute a coherent definition of synthetic biology with a distinct intellectual foundation and well-defined areas of application. This paper reviews the origins of the two fields and advances two distinct paradigms for each of them: that of unit operations for metabolic engineering and electronic circuits for synthetic biology. In this context, metabolic engineering is about engineering cell factories for the biological manufacturing of chemical and pharmaceutical products, whereas the main focus of synthetic biology is fundamental biological research facilitated by the use of synthetic DNA and genetic circuits.

Synergistic Synthetic Biology: Units in Concert

PubMed Central

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications. PMID:25022769

Synergistic Synthetic Biology: Units in Concert.

PubMed

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

Synthetic Biology: Engineering Living Systems from Biophysical Principles.

PubMed

Bartley, Bryan A; Kim, Kyung; Medley, J Kyle; Sauro, Herbert M

2017-03-28

Synthetic biology was founded as a biophysical discipline that sought explanations for the origins of life from chemical and physical first principles. Modern synthetic biology has been reinvented as an engineering discipline to design new organisms as well as to better understand fundamental biological mechanisms. However, success is still largely limited to the laboratory and transformative applications of synthetic biology are still in their infancy. Here, we review six principles of living systems and how they compare and contrast with engineered systems. We cite specific examples from the synthetic biology literature that illustrate these principles and speculate on their implications for further study. To fully realize the promise of synthetic biology, we must be aware of life's unique properties. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Meeting Report: Synthetic Biology Jamboree for Undergraduates

ERIC Educational Resources Information Center

Campbell, A. Malcolm

2005-01-01

The field of synthetic biology (the name is derived from an analogy to synthetic chemistry) has recognized itself as a "field" only since about 2002. Synthetic biology has gotten some high-profile attention recently, but most people are not aware the field even exists. Synthetic biologists apply engineering principles to genomic circuits to…

Feedback for reinforcement learning based brain-machine interfaces using confidence metrics.

PubMed

Prins, Noeline W; Sanchez, Justin C; Prasad, Abhishek

2017-06-01

For brain-machine interfaces (BMI) to be used in activities of daily living by paralyzed individuals, the BMI should be as autonomous as possible. One of the challenges is how the feedback is extracted and utilized in the BMI. Our long-term goal is to create autonomous BMIs that can utilize an evaluative feedback from the brain to update the decoding algorithm and use it intelligently in order to adapt the decoder. In this study, we show how to extract the necessary evaluative feedback from a biologically realistic (synthetic) source, use both the quantity and the quality of the feedback, and how that feedback information can be incorporated into a reinforcement learning (RL) controller architecture to maximize its performance. Motivated by the perception-action-reward cycle (PARC) in the brain which links reward for cognitive decision making and goal-directed behavior, we used a reward-based RL architecture named Actor-Critic RL as the model. Instead of using an error signal towards building an autonomous BMI, we envision to use a reward signal from the nucleus accumbens (NAcc) which plays a key role in the linking of reward to motor behaviors. To deal with the complexity and non-stationarity of biological reward signals, we used a confidence metric which was used to indicate the degree of feedback accuracy. This confidence was added to the Actor's weight update equation in the RL controller architecture. If the confidence was high (>0.2), the BMI decoder used this feedback to update its parameters. However, when the confidence was low, the BMI decoder ignored the feedback and did not update its parameters. The range between high confidence and low confidence was termed as the 'ambiguous' region. When the feedback was within this region, the BMI decoder updated its weight at a lower rate than when fully confident, which was decided by the confidence. We used two biologically realistic models to generate synthetic data for MI (Izhikevich model) and NAcc (Humphries model) to validate proposed controller architecture. In this work, we show how the overall performance of the BMI was improved by using a threshold close to the decision boundary to reject erroneous feedback. Additionally, we show the stability of the system improved when the feedback was used with a threshold. The result of this study is a step towards making BMIs autonomous. While our method is not fully autonomous, the results demonstrate that extensive training times necessary at the beginning of each BMI session can be significantly decreased. In our approach, decoder training time was only limited to 10 trials in the first BMI session. Subsequent sessions used previous session weights to initialize the decoder. We also present a method where the use of a threshold can be applied to any decoder with a feedback signal that is less than perfect so that erroneous feedback can be avoided and the stability of the system can be increased.

Feedback for reinforcement learning based brain-machine interfaces using confidence metrics

NASA Astrophysics Data System (ADS)

Prins, Noeline W.; Sanchez, Justin C.; Prasad, Abhishek

2017-06-01

Objective. For brain-machine interfaces (BMI) to be used in activities of daily living by paralyzed individuals, the BMI should be as autonomous as possible. One of the challenges is how the feedback is extracted and utilized in the BMI. Our long-term goal is to create autonomous BMIs that can utilize an evaluative feedback from the brain to update the decoding algorithm and use it intelligently in order to adapt the decoder. In this study, we show how to extract the necessary evaluative feedback from a biologically realistic (synthetic) source, use both the quantity and the quality of the feedback, and how that feedback information can be incorporated into a reinforcement learning (RL) controller architecture to maximize its performance. Approach. Motivated by the perception-action-reward cycle (PARC) in the brain which links reward for cognitive decision making and goal-directed behavior, we used a reward-based RL architecture named Actor-Critic RL as the model. Instead of using an error signal towards building an autonomous BMI, we envision to use a reward signal from the nucleus accumbens (NAcc) which plays a key role in the linking of reward to motor behaviors. To deal with the complexity and non-stationarity of biological reward signals, we used a confidence metric which was used to indicate the degree of feedback accuracy. This confidence was added to the Actor’s weight update equation in the RL controller architecture. If the confidence was high (>0.2), the BMI decoder used this feedback to update its parameters. However, when the confidence was low, the BMI decoder ignored the feedback and did not update its parameters. The range between high confidence and low confidence was termed as the ‘ambiguous’ region. When the feedback was within this region, the BMI decoder updated its weight at a lower rate than when fully confident, which was decided by the confidence. We used two biologically realistic models to generate synthetic data for MI (Izhikevich model) and NAcc (Humphries model) to validate proposed controller architecture. Main results. In this work, we show how the overall performance of the BMI was improved by using a threshold close to the decision boundary to reject erroneous feedback. Additionally, we show the stability of the system improved when the feedback was used with a threshold. Significance: The result of this study is a step towards making BMIs autonomous. While our method is not fully autonomous, the results demonstrate that extensive training times necessary at the beginning of each BMI session can be significantly decreased. In our approach, decoder training time was only limited to 10 trials in the first BMI session. Subsequent sessions used previous session weights to initialize the decoder. We also present a method where the use of a threshold can be applied to any decoder with a feedback signal that is less than perfect so that erroneous feedback can be avoided and the stability of the system can be increased.

Automated radiofrequency-based US measurement of common carotid intima-media thickness in RA patients treated with synthetic vs synthetic and biologic DMARDs.

PubMed

Naredo, Esperanza; Möller, Ingrid; Corrales, Alfonso; Bong, David A; Cobo-Ibáñez, Tatiana; Corominas, Hector; Garcia-Vivar, Ma Luz; Macarrón, Pilar; Navio, Teresa; Richi, Patricia; Iagnocco, Annamaria; Garrido, Jesús; Martínez-Hernández, David

2013-02-01

To compare the carotid intima-media thickness (IMT) assessed with automated radiofrequency-based US in RA patients treated with synthetic vs synthetic and biologic DMARDs and controls. Ninety-four RA patients and 94 sex- and age-matched controls were prospectively recruited at seven centres. Cardiovascular (CV) risk factors and co-morbidities, RA characteristics and therapy were recorded. Common carotid artery (CCA)-IMT was assessed in RA patients and controls with automated radiofrequency-based US by the same investigator at each centre. Forty-five (47.9%) RA patients had been treated with synthetic DMARDs and 49 (52.1%) with synthetic and biologic DMARDs. There were no significant differences between the RA patients and controls in demographics, CV co-morbidities and CV disease. There were significantly more smokers among RA patients treated with synthetic and biologic DMARDs (P = 0.036). Disease duration and duration of CS and synthetic DMARD therapy was significantly longer in RA patients treated with synthetic and biologic DMARDs (P < 0.0005). The mean CCA-IMT was significantly greater in RA patients treated only with synthetic DMARDs than in controls [591.4 (98.6) vs 562.1 (85.8); P = 0.035] and in RA patients treated with synthetic and biologic DMARDs [591.4 (98.6) vs 558.8 (95.3); P = 0.040). There was no significant difference between the mean CCA-IMT in RA patients treated with synthetic and biologic DMARDs and controls (P = 0.997). Our results suggest that radiofrequency-based measurement of CCA-IMT can discriminate between RA patients treated with synthetic DMARDs vs RA patients treated with synthetic and biologic DMARDs.

[New materia medica project: synthetic biology based bioactive metabolites research in medicinal plant].

PubMed

Wang, Yong

2017-03-25

In the last decade, synthetic biology research has been gradually transited from monocellular parts or devices toward more complex multicellular systems. The emerging plant synthetic biology is regarded as the "next chapter" of synthetic biology. The complex and diverse plant metabolism as the entry point, plant synthetic biology research not only helps us understand how real life is working, but also facilitates us to learn how to design and construct more complex artificial life. Bioactive compounds innovation and large-scale production are expected to be breakthrough with the redesigned plant metabolism as well. In this review, we discuss the research progress in plant synthetic biology and propose the new materia medica project to lift the level of traditional Chinese herbal medicine research.

A Powerful Toolkit for Synthetic Biology: Over 3.8 Billion Years of Evolution

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2010-01-01

The combination of evolutionary with engineering principles will enhance synthetic biology. Conversely, synthetic biology has the potential to enrich evolutionary biology by explaining why some adaptive space is empty, on Earth or elsewhere. Synthetic biology, the design and construction of artificial biological systems, substitutes bio-engineering for evolution, which is seen as an obstacle. But because evolution has produced the complexity and diversity of life, it provides a proven toolkit of genetic materials and principles available to synthetic biology. Evolution operates on the population level, with the populations composed of unique individuals that are historical entities. The source of genetic novelty includes mutation, gene regulation, sex, symbiosis, and interspecies gene transfer. At a phenotypic level, variation derives from regulatory control, replication and diversification of components, compartmentalization, sexual selection and speciation, among others. Variation is limited by physical constraints such as diffusion, and chemical constraints such as reaction rates and membrane fluidity. While some of these tools of evolution are currently in use in synthetic biology, all ought to be examined for utility. A hybrid approach of synthetic biology coupled with fine-tuning through evolution is suggested

A powerful toolkit for synthetic biology: Over 3.8 billion years of evolution.

PubMed

Rothschild, Lynn J

2010-04-01

The combination of evolutionary with engineering principles will enhance synthetic biology. Conversely, synthetic biology has the potential to enrich evolutionary biology by explaining why some adaptive space is empty, on Earth or elsewhere. Synthetic biology, the design and construction of artificial biological systems, substitutes bio-engineering for evolution, which is seen as an obstacle. But because evolution has produced the complexity and diversity of life, it provides a proven toolkit of genetic materials and principles available to synthetic biology. Evolution operates on the population level, with the populations composed of unique individuals that are historical entities. The source of genetic novelty includes mutation, gene regulation, sex, symbiosis, and interspecies gene transfer. At a phenotypic level, variation derives from regulatory control, replication and diversification of components, compartmentalization, sexual selection and speciation, among others. Variation is limited by physical constraints such as diffusion, and chemical constraints such as reaction rates and membrane fluidity. While some of these tools of evolution are currently in use in synthetic biology, all ought to be examined for utility. A hybrid approach of synthetic biology coupled with fine-tuning through evolution is suggested.

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

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.

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."

Synthetic Biology and Personalized Medicine

PubMed Central

Jain, K.K.

2013-01-01

Synthetic biology, application of synthetic chemistry to biology, is a broad term that covers the engineering of biological systems with structures and functions not found in nature to process information, manipulate chemicals, produce energy, maintain cell environment and enhance human health. Synthetic biology devices contribute not only to improve our understanding of disease mechanisms, but also provide novel diagnostic tools. Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs. The potential of synthetic genome, using an expanded genetic code that is designed for specific drug synthesis as well as delivery and activation of the drug in vivo by a pathological signal, was already pointed out during a lecture delivered at Kuwait University in 2005. Of two approaches to synthetic biology, top-down and bottom-up, the latter is more relevant to the development of personalized medicines as it provides more flexibility in constructing a partially synthetic cell from basic building blocks for a desired task. PMID:22907209

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.

2nd Congress on applied synthetic biology in Europe (Málaga, Spain, November 2013).

PubMed

Vetter, Beatrice V; Pantidos, Nikolaos; Edmundson, Matthew

2014-05-25

The second meeting organised by the EFB on the advances of applied synthetic biology in Europe was held in Málaga, Spain in November 2013. The potential for the broad application of synthetic biology was reflected in the five sessions of this meeting: synthetic biology for healthcare applications, tools and technologies for synthetic biology, production of recombinant proteins, synthetic plant biology, and biofuels and other small molecules. Outcomes from the meeting were that synthetic biology offers methods for rapid development of new strains that will result in decreased production costs, sustainable chemical production and new medical applications. Additionally, it also introduced novel ways to produce sustainable energy and biofuels, to find new alternatives for bioremediation and resource recovery, and environmentally friendly foodstuff production. All the above-mentioned advances could enable biotechnology to solve some of the major problems of Society. However, while there are still limitations in terms of lacking tools, standardisation and suitable host organisms, this meeting has laid a foundation providing cutting-edge concepts and techniques to ultimately convert the potential of synthetic biology into practice. Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Synthetic biology in the UK - An outline of plans and progress.

PubMed

Clarke, L J; Kitney, R I

2016-12-01

Synthetic biology is capable of delivering new solutions to key challenges spanning the bioeconomy, both nationally and internationally. Recognising this significant potential and the associated need to facilitate its translation and commercialisation the UK government commissioned the production of a national Synthetic Biology Roadmap in 2011, and subsequently provided crucial support to assist its implementation. Critical infrastructural investments have been made, and important strides made towards the development of an effectively connected community of practitioners and interest groups. A number of Synthetic Biology Research Centres, DNA Synthesis Foundries, a Centre for Doctoral Training, and an Innovation Knowledge Centre have been established, creating a nationally distributed and integrated network of complementary facilities and expertise. The UK Synthetic Biology Leadership Council published a UK Synthetic Biology Strategic Plan in 2016, increasing focus on the processes of translation and commercialisation. Over 50 start-ups, SMEs and larger companies are actively engaged in synthetic biology in the UK, and inward investments are starting to flow. Together these initiatives provide an important foundation for stimulating innovation, actively contributing to international research and development partnerships, and helping deliver useful benefits from synthetic biology in response to local and global needs and challenges.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update.

PubMed

Smolen, Josef S; Landewé, Robert; Bijlsma, Johannes; Burmester, Gerd; Chatzidionysiou, Katerina; Dougados, Maxime; Nam, Jackie; Ramiro, Sofia; Voshaar, Marieke; van Vollenhoven, Ronald; Aletaha, Daniel; Aringer, Martin; Boers, Maarten; Buckley, Chris D; Buttgereit, Frank; Bykerk, Vivian; Cardiel, Mario; Combe, Bernard; Cutolo, Maurizio; van Eijk-Hustings, Yvonne; Emery, Paul; Finckh, Axel; Gabay, Cem; Gomez-Reino, Juan; Gossec, Laure; Gottenberg, Jacques-Eric; Hazes, Johanna M W; Huizinga, Tom; Jani, Meghna; Karateev, Dmitry; Kouloumas, Marios; Kvien, Tore; Li, Zhanguo; Mariette, Xavier; McInnes, Iain; Mysler, Eduardo; Nash, Peter; Pavelka, Karel; Poór, Gyula; Richez, Christophe; van Riel, Piet; Rubbert-Roth, Andrea; Saag, Kenneth; da Silva, Jose; Stamm, Tanja; Takeuchi, Tsutomu; Westhovens, René; de Wit, Maarten; van der Heijde, Désirée

2017-06-01

Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to-or adding-another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies. 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/.

[Research progress of mammalian synthetic biology in biomedical field].

PubMed

Yang, Linfeng; Yin, Jianli; Wang, Meiyan; Ye, Haifeng

2017-03-25

Although still in its infant stage, synthetic biology has achieved remarkable development and progress during the past decade. Synthetic biology applies engineering principles to design and construct gene circuits uploaded into living cells or organisms to perform novel or improved functions, and it has been widely used in many fields. In this review, we describe the recent advances of mammalian synthetic biology for the treatment of diseases. We introduce common tools and design principles of synthetic gene circuits, and then we demonstrate open-loop gene circuits induced by different trigger molecules used in disease diagnosis and close-loop gene circuits used for biomedical applications. Finally, we discuss the perspectives and potential challenges of synthetic biology for clinical applications.

Standard biological parts knowledgebase.

PubMed

Galdzicki, Michal; Rodriguez, Cesar; Chandran, Deepak; Sauro, Herbert M; Gennari, John H

2011-02-24

We have created the Knowledgebase of Standard Biological Parts (SBPkb) as a publically accessible Semantic Web resource for synthetic biology (sbolstandard.org). The SBPkb allows researchers to query and retrieve standard biological parts for research and use in synthetic biology. Its initial version includes all of the information about parts stored in the Registry of Standard Biological Parts (partsregistry.org). SBPkb transforms this information so that it is computable, using our semantic framework for synthetic biology parts. This framework, known as SBOL-semantic, was built as part of the Synthetic Biology Open Language (SBOL), a project of the Synthetic Biology Data Exchange Group. SBOL-semantic represents commonly used synthetic biology entities, and its purpose is to improve the distribution and exchange of descriptions of biological parts. In this paper, we describe the data, our methods for transformation to SBPkb, and finally, we demonstrate the value of our knowledgebase with a set of sample queries. We use RDF technology and SPARQL queries to retrieve candidate "promoter" parts that are known to be both negatively and positively regulated. This method provides new web based data access to perform searches for parts that are not currently possible.

Efficacy and safety of biological and targeted-synthetic DMARDs: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis

PubMed Central

Regel, Andrea; van der Heijde, Désirée; Braun, Jürgen; Baraliakos, Xenofon; Landewé, Robert; Van den Bosch, Filip; Falzon, Louise; Ramiro, Sofia

2017-01-01

Objectives To update the evidence for the efficacy and safety of (b)biological and (ts)targeted-synthetic disease-modifying anti-rheumatic drugs (DMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2016 update of the Assessment of SpondyloArthritis international Society/European League Against Rheumatism (ASAS/EULAR) recommendations for the management of axSpA. Methods Systematic literature review (2009–2016) for randomised controlled trials (RCT), including long-term extensions, strategy trials and observational studies (the latter was only for safety assessment and a comparator was required). Interventions were any bDMARD or tsDMARD. All relevant efficacy and safety outcomes were included. Results 76 papers and 24 abstracts fulfilled the inclusion criteria. Large treatment effects were found both in radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA) for all tumour necrosis factor inhibitors (TNFi) (NNT to achieve ASAS40 response ranged between 2.6–5.2 for r-axSpA and 2.3–5.4 for nr-axSpA). For nr-axSpA, efficacy was superior for those who had objective signs of inflammation (positive C reactive protein or inflammation on MRI-SI). Secukinumab 150 mg has shown efficacy in two phase 3 RCTs (NNT to achieve ASAS40 response: 3.4 and 4.0). Ustekinumab and tofacitinib have shown positive results in phase 2/proof-of-concept trials; trials with apremilast, rituximab, interleukin (IL)-6 antagonists and abatacept have failed their primary end points. New (unknown) safety signals were not found in the trials but long-term observational safety data for TNFi are still scarce. Conclusions New evidence supports the efficacy and safety of TNFi both in r-axSpA and nr-axSpA. Secukinumab is the first drug targeting the IL-17 pathway in r-axSpA that has shown efficacy. PMID:28176964

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update

PubMed Central

Smolen, Josef S; Landewé, Robert; Breedveld, Ferdinand C; Buch, Maya; Burmester, Gerd; Dougados, Maxime; Emery, Paul; Gaujoux-Viala, Cécile; Gossec, Laure; Nam, Jackie; Ramiro, Sofia; Winthrop, Kevin; de Wit, Maarten; Aletaha, Daniel; Betteridge, Neil; Bijlsma, Johannes W J; Boers, Maarten; Buttgereit, Frank; Combe, Bernard; Cutolo, Maurizio; Damjanov, Nemanja; Hazes, Johanna M W; Kouloumas, Marios; Kvien, Tore K; Mariette, Xavier; Pavelka, Karel; van Riel, Piet L C M; Rubbert-Roth, Andrea; Scholte-Voshaar, Marieke; Scott, David L; Sokka-Isler, Tuulikki; Wong, John B; van der Heijde, Désirée

2014-01-01

In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at 3 months). Tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, biosimilars), abatacept, tocilizumab and, under certain circumstances, rituximab are essentially considered to have similar efficacy and safety. If the first bDMARD strategy fails, any other bDMARD may be used. The recommendations also address tofacitinib as a targeted sDMARD (tsDMARD), which is recommended, where licensed, after use of at least one bDMARD. Biosimilars are also addressed. These recommendations are intended to inform rheumatologists, patients, national rheumatology societies and other stakeholders about EULAR's most recent consensus on the management of RA with sDMARDs, glucocorticoids and bDMARDs. They are based on evidence and expert opinion and intended to improve outcome in patients with RA. PMID:24161836

BrisSynBio: a BBSRC/EPSRC-funded Synthetic Biology Research Centre.

PubMed

Sedgley, Kathleen R; Race, Paul R; Woolfson, Derek N

2016-06-15

BrisSynBio is the Bristol-based Biotechnology and Biological Sciences Research Council (BBSRC)/Engineering and Physical Sciences Research Council (EPSRC)-funded Synthetic Biology Research Centre. It is one of six such Centres in the U.K. BrisSynBio's emphasis is on rational and predictive bimolecular modelling, design and engineering in the context of synthetic biology. It trains the next generation of synthetic biologists in these approaches, to facilitate translation of fundamental synthetic biology research to industry and the clinic, and to do this within an innovative and responsible research framework. © 2016 The Author(s).

Finding Hope in Synthetic Biology.

PubMed

Takala, Tuija

2017-04-01

For some, synthetic biology represents great hope in offering possible solutions to many of the world's biggest problems, from hunger to sustainable development. Others remain fearful of the harmful uses, such as bioweapons, that synthetic biology can lend itself to, and most hold that issues of biosafety are of utmost importance. In this article, I will evaluate these points of view and conclude that although the biggest promises of synthetic biology are unlikely to become reality, and the probability of accidents is fairly substantial, synthetic biology could still be seen to benefit humanity by enhancing our ethical understanding and by offering a boost to world economy.

European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.

PubMed

Gossec, L; Smolen, J S; Ramiro, S; de Wit, M; Cutolo, M; Dougados, M; Emery, P; Landewé, R; Oliver, S; Aletaha, D; Betteridge, N; Braun, J; Burmester, G; Cañete, J D; Damjanov, N; FitzGerald, O; Haglund, E; Helliwell, P; Kvien, T K; Lories, R; Luger, T; Maccarone, M; Marzo-Ortega, H; McGonagle, D; McInnes, I B; Olivieri, I; Pavelka, K; Schett, G; Sieper, J; van den Bosch, F; Veale, D J; Wollenhaupt, J; Zink, A; van der Heijde, D

2016-03-01

Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion. 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/

Knowledge-making distinctions in synthetic biology.

PubMed

O'Malley, Maureen A; Powell, Alexander; Davies, Jonathan F; Calvert, Jane

2008-01-01

Synthetic biology is an increasingly high-profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA-based device construction, genome-driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie into two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge-making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems. (c) 2007 Wiley Periodicals, Inc.

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.

Beyond patchwork precaution in the dual-use governance of synthetic biology.

PubMed

Kelle, Alexander

2013-09-01

The emergence of synthetic biology holds the potential of a major breakthrough in the life sciences by transforming biology into a predictive science. The dual-use characteristics of similar breakthroughs during the twentieth century have led to the application of benignly intended research in e.g. virology, bacteriology and aerobiology in offensive biological weapons programmes. Against this background the article raises the question whether the precautionary governance of synthetic biology can aid in preventing this techno-science witnessing the same fate? In order to address this question, this paper proceeds in four steps: it firstly introduces the emerging techno-science of synthetic biology and presents some of its potential beneficial applications. It secondly analyses contributions to the bioethical discourse on synthetic biology as well as precautionary reasoning and its application to life science research in general and synthetic biology more specifically. The paper then identifies manifestations of a moderate precautionary principle in the emerging synthetic biology dual-use governance discourse. Using a dual-use governance matrix as heuristic device to analyse some of the proposed measures, it concludes that the identified measures can best be described as "patchwork precaution" and that a more systematic approach to construct a web of dual-use precaution for synthetic biology is needed in order to guard more effectively against the field's future misuse for harmful applications.

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.

Exploring Synthetic and Systems Biology at the University of Edinburgh.

PubMed

Fletcher, Liz; Rosser, Susan; Elfick, Alistair

2016-06-15

The Centre for Synthetic and Systems Biology ('SynthSys') was originally established in 2007 as the Centre for Integrative Systems Biology, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). Today, SynthSys embraces an extensive multidisciplinary community of more than 200 researchers from across the University with a common interest in synthetic and systems biology. Our research is broad and deep, addressing a diversity of scientific questions, with wide ranging impact. We bring together the power of synthetic biology and systems approaches to focus on three core thematic areas: industrial biotechnology, agriculture and the environment, and medicine and healthcare. In October 2015, we opened a newly refurbished building as a physical hub for our new U.K. Centre for Mammalian Synthetic Biology funded by the BBSRC/EPSRC/MRC as part of the U.K. Research Councils' Synthetic Biology for Growth programme. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Artificial intelligence and synthetic biology: A tri-temporal contribution.

PubMed

Bianchini, Francesco

2016-10-01

Artificial intelligence can make numerous contributions to synthetic biology. I would like to suggest three that are related to the past, present and future of artificial intelligence. From the past, works in biology and artificial systems by Turing and von Neumann prove highly interesting to explore within the new framework of synthetic biology, especially with regard to the notions of self-modification and self-replication and their links to emergence and the bottom-up approach. The current epistemological inquiry into emergence and research on swarm intelligence, superorganisms and biologically inspired cognitive architecture may lead to new achievements on the possibilities of synthetic biology in explaining cognitive processes. Finally, the present-day discussion on the future of artificial intelligence and the rise of superintelligence may point to some research trends for the future of synthetic biology and help to better define the boundary of notions such as "life", "cognition", "artificial" and "natural", as well as their interconnections in theoretical synthetic biology. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Synthetic biology between technoscience and thing knowledge.

PubMed

Gelfert, Axel

2013-06-01

Synthetic biology presents a challenge to traditional accounts of biology: Whereas traditional biology emphasizes the evolvability, variability, and heterogeneity of living organisms, synthetic biology envisions a future of homogeneous, humanly engineered biological systems that may be combined in modular fashion. The present paper approaches this challenge from the perspective of the epistemology of technoscience. In particular, it is argued that synthetic-biological artifacts lend themselves to an analysis in terms of what has been called 'thing knowledge'. As such, they should neither be regarded as the simple outcome of applying theoretical knowledge and engineering principles to specific technological problems, nor should they be treated as mere sources of new evidence in the general pursuit of scientific understanding. Instead, synthetic-biological artifacts should be viewed as partly autonomous research objects which, qua their material-biological constitution, embody knowledge about the natural world-knowledge that, in turn, can be accessed via continuous experimental interrogation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Developments in the Tools and Methodologies of Synthetic Biology

PubMed Central

Kelwick, Richard; MacDonald, James T.; Webb, Alexander J.; Freemont, Paul

2014-01-01

Synthetic biology is principally concerned with the rational design and engineering of biologically based parts, devices, or systems. However, biological systems are generally complex and unpredictable, and are therefore, intrinsically difficult to engineer. In order to address these fundamental challenges, synthetic biology is aiming to unify a “body of knowledge” from several foundational scientific fields, within the context of a set of engineering principles. This shift in perspective is enabling synthetic biologists to address complexity, such that robust biological systems can be designed, assembled, and tested as part of a biological design cycle. The design cycle takes a forward-design approach in which a biological system is specified, modeled, analyzed, assembled, and its functionality tested. At each stage of the design cycle, an expanding repertoire of tools is being developed. In this review, we highlight several of these tools in terms of their applications and benefits to the synthetic biology community. PMID:25505788

Computer-aided design of biological circuits using TinkerCell

PubMed Central

Bergmann, Frank T; Sauro, Herbert M

2010-01-01

Synthetic biology is an engineering discipline that builds on modeling practices from systems biology and wet-lab techniques from genetic engineering. As synthetic biology advances, efficient procedures will be developed that will allow a synthetic biologist to design, analyze and build biological networks. In this idealized pipeline, computer-aided design (CAD) is a necessary component. The role of a CAD application would be to allow efficient transition from a general design to a final product. TinkerCell is a design tool for serving this purpose in synthetic biology. In TinkerCell, users build biological networks using biological parts and modules. The network can be analyzed using one of several functions provided by TinkerCell or custom programs from third-party sources. Since best practices for modeling and constructing synthetic biology networks have not yet been established, TinkerCell is designed as a flexible and extensible application that can adjust itself to changes in the field. PMID:21327060

Computational protein design-the next generation tool to expand synthetic biology applications.

PubMed

Gainza-Cirauqui, Pablo; Correia, Bruno Emanuel

2018-05-02

One powerful approach to engineer synthetic biology pathways is the assembly of proteins sourced from one or more natural organisms. However, synthetic pathways often require custom functions or biophysical properties not displayed by natural proteins, limitations that could be overcome through modern protein engineering techniques. Structure-based computational protein design is a powerful tool to engineer new functional capabilities in proteins, and it is beginning to have a profound impact in synthetic biology. Here, we review efforts to increase the capabilities of synthetic biology using computational protein design. We focus primarily on computationally designed proteins not only validated in vitro, but also shown to modulate different activities in living cells. Efforts made to validate computational designs in cells can illustrate both the challenges and opportunities in the intersection of protein design and synthetic biology. We also highlight protein design approaches, which although not validated as conveyors of new cellular function in situ, may have rapid and innovative applications in synthetic biology. We foresee that in the near-future, computational protein design will vastly expand the functional capabilities of synthetic cells. Copyright © 2018. Published by Elsevier Ltd.

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

Building Better Scientists through Cross-Disciplinary Collaboration in Synthetic Biology: A Report from the Genome Consortium for Active Teaching Workshop 2010

ERIC Educational Resources Information Center

Wolyniak, Michael J.; Alvarez, Consuelo J.; Chandrasekaran, Vidya; Grana, Theresa M.; Holgado, Andrea; Jones, Christopher J.; Morris, Robert W.; Pereira, Anil L.; Stamm, Joyce; Washington, Talitha M.; Yang, Yixin

2010-01-01

Synthetic biology is the application of engineering and mathematical principles to develop novel biological devices and circuits. What separates synthetic biology from traditional molecular biology is the development of standardized interchangeable DNA "parts," just as advances in engineering in the nineteenth century brought about standardized…

Standard Biological Parts Knowledgebase

PubMed Central

Galdzicki, Michal; Rodriguez, Cesar; Chandran, Deepak; Sauro, Herbert M.; Gennari, John H.

2011-01-01

We have created the Knowledgebase of Standard Biological Parts (SBPkb) as a publically accessible Semantic Web resource for synthetic biology (sbolstandard.org). The SBPkb allows researchers to query and retrieve standard biological parts for research and use in synthetic biology. Its initial version includes all of the information about parts stored in the Registry of Standard Biological Parts (partsregistry.org). SBPkb transforms this information so that it is computable, using our semantic framework for synthetic biology parts. This framework, known as SBOL-semantic, was built as part of the Synthetic Biology Open Language (SBOL), a project of the Synthetic Biology Data Exchange Group. SBOL-semantic represents commonly used synthetic biology entities, and its purpose is to improve the distribution and exchange of descriptions of biological parts. In this paper, we describe the data, our methods for transformation to SBPkb, and finally, we demonstrate the value of our knowledgebase with a set of sample queries. We use RDF technology and SPARQL queries to retrieve candidate “promoter” parts that are known to be both negatively and positively regulated. This method provides new web based data access to perform searches for parts that are not currently possible. PMID:21390321

Biomedically relevant circuit-design strategies in mammalian synthetic biology

PubMed Central

Bacchus, William; Aubel, Dominique; Fussenegger, Martin

2013-01-01

The development and progress in synthetic biology has been remarkable. Although still in its infancy, synthetic biology has achieved much during the past decade. Improvements in genetic circuit design have increased the potential for clinical applicability of synthetic biology research. What began as simple transcriptional gene switches has rapidly developed into a variety of complex regulatory circuits based on the transcriptional, translational and post-translational regulation. Instead of compounds with potential pharmacologic side effects, the inducer molecules now used are metabolites of the human body and even members of native cell signaling pathways. In this review, we address recent progress in mammalian synthetic biology circuit design and focus on how novel designs push synthetic biology toward clinical implementation. Groundbreaking research on the implementation of optogenetics and intercellular communications is addressed, as particularly optogenetics provides unprecedented opportunities for clinical application. Along with an increase in synthetic network complexity, multicellular systems are now being used to provide a platform for next-generation circuit design. PMID:24061539

The Role of Synthetic Biology in NASA's Missions

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2016-01-01

The time has come to for NASA to exploit synthetic biology in pursuit of its missions, including aeronautics, earth science, astrobiology and most notably, human exploration. Conversely, NASA advances the fundamental technology of synthetic biology as no one else can because of its unique expertise in the origin of life and life in extreme environments, including the potential for alternate life forms. This enables unique, creative "game changing" advances. NASA's requirement for minimizing upmass in flight will also drive the field toward miniaturization and automation. These drivers will greatly increase the utility of synthetic biology solutions for military, health in remote areas and commercial purposes. To this end, we have begun a program at NASA to explore the use of synthetic biology in NASA's missions, particular space exploration. As part of this program, we began hosting an iGEM team of undergraduates drawn from Brown and Stanford Universities to conduct synthetic biology research at NASA Ames Research Center. The 2011 team (http://2011.igem.org/Team:Brown-Stanford) produced an award-winning project on using synthetic biology as a basis for a human Mars settlement.

On Beyond Star Trek, the Role of Synthetic Biology in Nasa's Missions

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2016-01-01

The time has come to for NASA to exploit the nascent field of synthetic biology in pursuit of its mission, including aeronautics, earth science, astrobiology and notably, human exploration. Conversely, NASA advances the fundamental technology of synthetic biology as no one else can because of its unique expertise in the origin of life and life in extreme environments, including the potential for alternate life forms. This enables unique, creative "game changing" advances. NASA's requirement for minimizing upmass in flight will also drive the field toward miniaturization and automation. These drivers will greatly increase the utility of synthetic biology solutions for military, health in remote areas and commercial purposes. To this end, we have begun a program at NASA to explore the use of synthetic biology in NASA's missions, particularly space exploration. As part of this program, we began hosting an iGEM team of undergraduates drawn from Brown and Stanford Universities to conduct synthetic biology research at NASA Ames Research Center. The 2011 team (http://2011.igem.org/Team:Brown-Stanford) produced an award-winning project on using synthetic biology as a basis for a human Mars settlement and the 2012 team has expanded the use of synthetic biology to estimate the potential for life in the clouds of other planets (http://2012.igem.org/Team:Stanford-Brown; http://www.calacademy.org/sciencetoday/igem-competition/). More recent projects from the Stanford-Brown team have expanded our ideas of how synthetic biology can aid NASA's missions from "Synthetic BioCommunication" (http://2013.igem.org/Team:Stanford-Brown) to a "Biodegradable UAS (drone)" in collaboration with Spelman College (http://2014.igem.org/Team:StanfordBrownSpelman#SBS%20iGEM) and most recently, "Self-Folding Origami" (http://2015.igem.org/Team:Stanford-Brown), the winner of the 2015 award for Manufacturing.

Parts plus pipes: synthetic biology approaches to metabolic engineering

PubMed Central

Boyle, Patrick M.; Silver, Pamela A.

2011-01-01

Synthetic biologists combine modular biological “parts” to create higher-order devices. Metabolic engineers construct biological “pipes” by optimizing the microbial conversion of basic substrates to desired compounds. Many scientists work at the intersection of these two philosophies, employing synthetic devices to enhance metabolic engineering efforts. These integrated approaches promise to do more than simply improve product yields; they can expand the array of products that are tractable to produce biologically. In this review, we explore the application of synthetic biology techniques to next-generation metabolic engineering challenges, as well as the emerging engineering principles for biological design. PMID:22037345

Is synthetic biology mechanical biology?

PubMed

Holm, Sune

2015-12-01

A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

Diffusion of synthetic biology: a challenge to biosafety.

PubMed

Schmidt, Markus

2008-06-01

One of the main aims of synthetic biology is to make biology easier to engineer. Major efforts in synthetic biology are made to develop a toolbox to design biological systems without having to go through a massive research and technology process. With this "de-skilling" agenda, synthetic biology might finally unleash the full potential of biotechnology and spark a wave of innovation, as more and more people have the necessary skills to engineer biology. But this ultimate domestication of biology could easily lead to unprecedented safety challenges that need to be addressed: more and more people outside the traditional biotechnology community will create self-replicating machines (life) for civil and defence applications, "biohackers" will engineer new life forms at their kitchen table; and illicit substances will be produced synthetically and much cheaper. Such a scenario is a messy and dangerous one, and we need to think about appropriate safety standards now.

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

SynBioSS designer: a web-based tool for the automated generation of kinetic models for synthetic biological constructs

PubMed Central

Weeding, Emma; Houle, Jason

2010-01-01

Modeling tools can play an important role in synthetic biology the same way modeling helps in other engineering disciplines: simulations can quickly probe mechanisms and provide a clear picture of how different components influence the behavior of the whole. We present a brief review of available tools and present SynBioSS Designer. The Synthetic Biology Software Suite (SynBioSS) is used for the generation, storing, retrieval and quantitative simulation of synthetic biological networks. SynBioSS consists of three distinct components: the Desktop Simulator, the Wiki, and the Designer. SynBioSS Designer takes as input molecular parts involved in gene expression and regulation (e.g. promoters, transcription factors, ribosome binding sites, etc.), and automatically generates complete networks of reactions that represent transcription, translation, regulation, induction and degradation of those parts. Effectively, Designer uses DNA sequences as input and generates networks of biomolecular reactions as output. In this paper we describe how Designer uses universal principles of molecular biology to generate models of any arbitrary synthetic biological system. These models are useful as they explain biological phenotypic complexity in mechanistic terms. In turn, such mechanistic explanations can assist in designing synthetic biological systems. We also discuss, giving practical guidance to users, how Designer interfaces with the Registry of Standard Biological Parts, the de facto compendium of parts used in synthetic biology applications. PMID:20639523

Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

PubMed Central

Chen, Bor-Sen; Wu, Chia-Chou

2013-01-01

Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii) system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv) systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering. PMID:24709875

Systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

PubMed

Chen, Bor-Sen; Wu, Chia-Chou

2013-10-11

Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii) system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv) systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

Synthetic Biology: Mapping the Scientific Landscape

PubMed Central

Oldham, Paul; Hall, Stephen; Burton, Geoff

2012-01-01

This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA) of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves. PMID:22539946

Computer-aided design of biological circuits using TinkerCell.

PubMed

Chandran, Deepak; Bergmann, Frank T; Sauro, Herbert M

2010-01-01

Synthetic biology is an engineering discipline that builds on modeling practices from systems biology and wet-lab techniques from genetic engineering. As synthetic biology advances, efficient procedures will be developed that will allow a synthetic biologist to design, analyze, and build biological networks. In this idealized pipeline, computer-aided design (CAD) is a necessary component. The role of a CAD application would be to allow efficient transition from a general design to a final product. TinkerCell is a design tool for serving this purpose in synthetic biology. In TinkerCell, users build biological networks using biological parts and modules. The network can be analyzed using one of several functions provided by TinkerCell or custom programs from third-party sources. Since best practices for modeling and constructing synthetic biology networks have not yet been established, TinkerCell is designed as a flexible and extensible application that can adjust itself to changes in the field. © 2010 Landes Bioscience

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.

Synthetic biology through biomolecular design and engineering.

PubMed

Channon, Kevin; Bromley, Elizabeth H C; Woolfson, Derek N

2008-08-01

Synthetic biology is a rapidly growing field that has emerged in a global, multidisciplinary effort among biologists, chemists, engineers, physicists, and mathematicians. Broadly, the field has two complementary goals: To improve understanding of biological systems through mimicry and to produce bio-orthogonal systems with new functions. Here we review the area specifically with reference to the concept of synthetic biology space, that is, a hierarchy of components for, and approaches to generating new synthetic and functional systems to test, advance, and apply our understanding of biological systems. In keeping with this issue of Current Opinion in Structural Biology, we focus largely on the design and engineering of biomolecule-based components and systems.

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.

Misconceptions of Synthetic Biology: Lessons from an Interdisciplinary Summer School

NASA Technical Reports Server (NTRS)

Verseux, Cyprien; Acevedo-Rocha, Carlos G.; Chizzolini, Fabio; Rothschild, Lynn J.

2016-01-01

In 2014, an international group of scholars from various fields analysed the "societal dimensions" of synthetic biology in an interdisciplinary summer school. Here, we report and discuss the biologists' observations on the general perception of synthetic biology by non-biologists who took part in this event. Most attendees mainly associated synthetic biology with contributions from the best-known public figures of the field, rarely mentioning other scientists. Media extrapolations of those contributions appeared to have created unrealistic expectations and irrelevant fears that were widely disconnected from the current research in synthetic biology. Another observation was that when debating developments in synthetic biology, semantics strongly mattered: depending on the terms used to present an application of synthetic biology, attendees reacted in radically different ways. For example, using the term "GMOs" (genetically modified organisms) rather than the term "genetic engineering" led to very different reactions. Stimulating debates also happened with participants having unanticipated points of view, for instance biocentrist ethicists who argued that engineered microbes should not be used for human purposes. Another communication challenge emerged from the connotations and inaccuracies surrounding the word "life", which impaired constructive debates, thus leading to misconceptions about the abilities of scientists to engineer or even create living organisms. Finally, it appeared that synthetic biologists tend to overestimate the knowledge of non-biologists, further affecting communication. The motivation and ability of synthetic biologists to communicate their work outside their research field needs to be fostered, notably towards policymakers who need a more accurate and technical understanding of the field to make informed decisions. Interdisciplinary events gathering scholars working in and around synthetic biology are an effective tool in addressing those issues.

Synthetic Biology and the Translational Imperative.

PubMed

Heidari Feidt, Raheleh; Ienca, Marcello; Elger, Bernice Simone; Folcher, Marc

2017-12-18

Advances at the interface between the biological sciences and engineering are giving rise to emerging research fields such as synthetic biology. Harnessing the potential of synthetic biology requires timely and adequate translation into clinical practice. However, the translational research enterprise is currently facing fundamental obstacles that slow down the transition of scientific discoveries from the laboratory to the patient bedside. These obstacles including scarce financial resources and deficiency of organizational and logistic settings are widely discussed as primary impediments to translational research. In addition, a number of socio-ethical considerations inherent in translational research need to be addressed. As the translational capacity of synthetic biology is tightly linked to its social acceptance and ethical approval, ethical limitations may-together with financial and organizational problems-be co-determinants of suboptimal translation. Therefore, an early assessment of such limitations will contribute to proactively favor successful translation and prevent the promising potential of synthetic biology from remaining under-expressed. Through the discussion of two case-specific inventions in synthetic biology and their associated ethical implications, we illustrate the socio-ethical challenges ahead in the process of implementing synthetic biology into clinical practice. Since reducing the translational lag is essential for delivering the benefits of basic biomedical research to society at large and promoting global health, we advocate a moral obligation to accelerating translational research: the "translational imperative."

Grand challenges in space synthetic biology

PubMed Central

Montague, Michael G.; Cumbers, John; Hogan, John A.

2015-01-01

Space synthetic biology is a branch of biotechnology dedicated to engineering biological systems for space exploration, industry and science. There is significant public and private interest in designing robust and reliable organisms that can assist on long-duration astronaut missions. Recent work has also demonstrated that such synthetic biology is a feasible payload minimization and life support approach as well. This article identifies the challenges and opportunities that lie ahead in the field of space synthetic biology, while highlighting relevant progress. It also outlines anticipated broader benefits from this field, because space engineering advances will drive technological innovation on Earth. PMID:26631337

Synthetic biology and molecular genetics in non-conventional yeasts: Current tools and future advances.

PubMed

Wagner, James M; Alper, Hal S

2016-04-01

Coupling the tools of synthetic biology with traditional molecular genetic techniques can enable the rapid prototyping and optimization of yeast strains. While the era of yeast synthetic biology began in the well-characterized model organism Saccharomyces cerevisiae, it is swiftly expanding to include non-conventional yeast production systems such as Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. These yeasts already have roles in the manufacture of vaccines, therapeutic proteins, food additives, and biorenewable chemicals, but recent synthetic biology advances have the potential to greatly expand and diversify their impact on biotechnology. In this review, we summarize the development of synthetic biological tools (including promoters and terminators) and enabling molecular genetics approaches that have been applied in these four promising alternative biomanufacturing platforms. An emphasis is placed on synthetic parts and genome editing tools. Finally, we discuss examples of synthetic tools developed in other organisms that can be adapted or optimized for these hosts in the near future. Copyright © 2015 Elsevier Inc. All rights reserved.

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

From bricolage to BioBricks™: Synthetic biology and rational design.

PubMed

Lewens, Tim

2013-12-01

Synthetic biology is often described as a project that applies rational design methods to the organic world. Although humans have influenced organic lineages in many ways, it is nonetheless reasonable to place synthetic biology towards one end of a continuum between purely 'blind' processes of organic modification at one extreme, and wholly rational, design-led processes at the other. An example from evolutionary electronics illustrates some of the constraints imposed by the rational design methodology itself. These constraints reinforce the limitations of the synthetic biology ideal, limitations that are often freely acknowledged by synthetic biology's own practitioners. The synthetic biology methodology reflects a series of constraints imposed on finite human designers who wish, as far as is practicable, to communicate with each other and to intervene in nature in reasonably targeted and well-understood ways. This is better understood as indicative of an underlying awareness of human limitations, rather than as expressive of an objectionable impulse to mastery over nature. Copyright © 2013 Elsevier Ltd. All rights reserved.

Approaches to chemical synthetic biology.

PubMed

Chiarabelli, Cristiano; Stano, Pasquale; Anella, Fabrizio; Carrara, Paolo; Luisi, Pier Luigi

2012-07-16

Synthetic biology is first represented in terms of two complementary aspects, the bio-engineering one, based on the genetic manipulation of extant microbial forms in order to obtain forms of life which do not exist in nature; and the chemical synthetic biology, an approach mostly based on chemical manipulation for the laboratory synthesis of biological structures that do not exist in nature. The paper is mostly devoted to shortly review chemical synthetic biology projects currently carried out in our laboratory. In particular, we describe: the minimal cell project, then the "Never Born Proteins" and lastly the Never Born RNAs. We describe and critically analyze the main results, emphasizing the possible relevance of chemical synthetic biology for the progress in basic science and biotechnology. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Synthetic biology and the technicity of biofuels.

PubMed

Mackenzie, Adrian

2013-06-01

The principal existing real-world application of synthetic biology is biofuels. Several 'next generation biofuel' companies-Synthetic Genomics, Amyris and Joule Unlimited Technologies-claim to be using synthetic biology to make biofuels. The irony of this is that highly advanced science and engineering serves the very mundane and familiar realm of transport. Despite their rather prosaic nature, biofuels could offer an interesting way to highlight the novelty of synthetic biology from several angles at once. Drawing on the French philosopher of technology and biology Gilbert Simondon, we can understand biofuels as technical objects whose genesis involves processes of concretisation that negotiate between heterogeneous geographical, biological, technical, scientific and commercial realities. Simondon's notion of technicity, the degree of concretisation of a technical object, usefully conceptualises this relationality. Viewed in terms of technicity, we might understand better how technical entities, elements, and ensembles are coming into being in the name of synthetic biology. The broader argument here is that when we seek to identify the newness of disciplines, their newness might be less epistemic and more logistic. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Microfluidic technologies for synthetic biology.

PubMed

Vinuselvi, Parisutham; Park, Seongyong; Kim, Minseok; Park, Jung Min; Kim, Taesung; Lee, Sung Kuk

2011-01-01

Microfluidic technologies have shown powerful abilities for reducing cost, time, and labor, and at the same time, for increasing accuracy, throughput, and performance in the analysis of biological and biochemical samples compared with the conventional, macroscale instruments. Synthetic biology is an emerging field of biology and has drawn much attraction due to its potential to create novel, functional biological parts and systems for special purposes. Since it is believed that the development of synthetic biology can be accelerated through the use of microfluidic technology, in this review work we focus our discussion on the latest microfluidic technologies that can provide unprecedented means in synthetic biology for dynamic profiling of gene expression/regulation with high resolution, highly sensitive on-chip and off-chip detection of metabolites, and whole-cell analysis.

Applications of cell-free protein synthesis in synthetic biology: Interfacing bio-machinery with synthetic environments.

PubMed

Lee, Kyung-Ho; Kim, Dong-Myung

2013-11-01

Synthetic biology is built on the synthesis, engineering, and assembly of biological parts. Proteins are the first components considered for the construction of systems with designed biological functions because proteins carry out most of the biological functions and chemical reactions inside cells. Protein synthesis is considered to comprise the most basic levels of the hierarchical structure of synthetic biology. Cell-free protein synthesis has emerged as a powerful technology that can potentially transform the concept of bioprocesses. With the ability to harness the synthetic power of biology without many of the constraints of cell-based systems, cell-free protein synthesis enables the rapid creation of protein molecules from diverse sources of genetic information. Cell-free protein synthesis is virtually free from the intrinsic constraints of cell-based methods and offers greater flexibility in system design and manipulability of biological synthetic machinery. Among its potential applications, cell-free protein synthesis can be combined with various man-made devices for rapid functional analysis of genomic sequences. This review covers recent efforts to integrate cell-free protein synthesis with various reaction devices and analytical platforms. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Prospects for Applying Synthetic Biology to Toxicology: Future Opportunities and Current Limitations for the Repurposing of Cytochrome P450 Systems.

PubMed

Behrendorff, James B Y H; Gillam, Elizabeth M J

2017-01-17

The 30 years since the inception of Chemical Research in Toxicology, game-changing advances in chemical and molecular biology, the fundamental disciplines underpinning molecular toxicology, have been made. While these have led to important advances in the study of mechanisms by which chemicals damage cells and systems, there has been less focus on applying these advances to prediction, detection, and mitigation of toxicity. Over the last ∼15 years, synthetic biology, the repurposing of biological "parts" in systems engineered for useful ends, has been explored in other areas of the biomedical and life sciences, for such applications as detecting metabolites, drug discovery and delivery, investigating disease mechanisms, improving medical treatment, and producing useful chemicals. These examples provide models for the application of synthetic biology to toxicology, which, for the most part, has not yet benefited from such approaches. In this perspective, we review the synthetic biology approaches that have been applied to date and speculate on possible short to medium term and "blue sky" aspirations for synthetic biology, particularly in clinical and environmental toxicology. Finally, we point out key hurdles that must be overcome for the full potential of synthetic biology to be realized.

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-offs on Phenotype Robustness in Biological Networks. Part III: Synthetic Gene Networks in Synthetic Biology

PubMed Central

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties that are observed in biological systems at many 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 large enough to confer: intrinsic robustness for tolerating intrinsic parameter fluctuations; genetic robustness for buffering genetic variations; and environmental robustness for resisting environmental disturbances. Network robustness is needed so phenotype stability of biological network can be maintained, guaranteeing phenotype robustness. Synthetic biology is foreseen to have important applications in biotechnology and medicine; it is expected to contribute significantly to a better understanding of functioning of complex biological systems. This paper presents a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation for synthetic gene networks in synthetic biology. Further, from the unifying mathematical framework, we found that the phenotype robustness criterion for synthetic gene networks is the following: if intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness, then 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 synthetic biology can also be investigated through corresponding phenotype robustness criteria from the systematic point of view. Finally, a robust synthetic design that involves network evolution algorithms with desired behavior under intrinsic parameter fluctuations, genetic variations, and environmental disturbances, is also proposed, together with a simulation example. PMID:23515190

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-offs on Phenotype Robustness in Biological Networks. Part III: Synthetic Gene Networks in Synthetic Biology.

PubMed

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties that are observed in biological systems at many 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 large enough to confer: intrinsic robustness for tolerating intrinsic parameter fluctuations; genetic robustness for buffering genetic variations; and environmental robustness for resisting environmental disturbances. Network robustness is needed so phenotype stability of biological network can be maintained, guaranteeing phenotype robustness. Synthetic biology is foreseen to have important applications in biotechnology and medicine; it is expected to contribute significantly to a better understanding of functioning of complex biological systems. This paper presents a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation for synthetic gene networks in synthetic biology. Further, from the unifying mathematical framework, we found that the phenotype robustness criterion for synthetic gene networks is the following: if intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness, then 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 synthetic biology can also be investigated through corresponding phenotype robustness criteria from the systematic point of view. Finally, a robust synthetic design that involves network evolution algorithms with desired behavior under intrinsic parameter fluctuations, genetic variations, and environmental disturbances, is also proposed, together with a simulation example.

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.

[Smart therapeutics based on synthetic gene circuits].

PubMed

Peng, Shuguang; Xie, Zhen

2017-03-25

Synthetic biology has an important impact on biology research since its birth. Applying the thought and methods that reference from electrical engineering, synthetic biology uncovers many regulatory mechanisms of life systems, transforms and expands a series of biological components. Therefore, it brings a wide range of biomedical applications, including providing new ideas for disease diagnosis and treatment. This review describes the latest advances in the field of disease diagnosis and therapy based on mammalian cell or bacterial synthetic gene circuits, and provides new ideas for future smart therapy design.

Synthetic Biology for Specialty Chemicals.

PubMed

Markham, Kelly A; Alper, Hal S

2015-01-01

In this review, we address recent advances in the field of synthetic biology and describe how those tools have been applied to produce a wide variety of chemicals in microorganisms. Here we classify the expansion of the synthetic biology toolbox into three different categories based on their primary function in strain engineering-for design, for construction, and for optimization. Next, focusing on recent years, we look at how chemicals have been produced using these new synthetic biology tools. Advances in producing fuels are briefly described, followed by a more thorough treatment of commodity chemicals, specialty chemicals, pharmaceuticals, and nutraceuticals. Throughout this review, an emphasis is placed on how synthetic biology tools are applied to strain engineering. Finally, we discuss organism and host strain diversity and provide a future outlook in the field.

Defining the Synthetic Biology Supply Chain.

PubMed

Frazar, Sarah L; Hund, Gretchen E; Bonheyo, George T; Diggans, James; Bartholomew, Rachel A; Gehrig, Lindsey; Greaves, Mark

Several recent articles have described risks posed by synthetic biology and spurred vigorous discussion in the scientific, commercial, and government communities about how to best detect, prevent, regulate, and respond to these risks. The Pacific Northwest National Laboratory's (PNNL) deep experience working with dual-use technologies for the nuclear industry has shown that analysis of supply chains can reveal security vulnerabilities and ways to mitigate security risk without hindering beneficial research and commerce. In this article, a team of experts in synthetic biology, data analytics, and national security describe the overall supply chain surrounding synthetic biology to illustrate new insights about the effectiveness of current regulations, the possible need for different screening approaches, and new technical solutions that could help identify or mitigate risks in the synthetic biology supply chain.

Synthetic biology: An emerging research field in China

PubMed Central

Pei, Lei; Schmidt, Markus; Wei, Wei

2011-01-01

Synthetic biology is considered as an emerging research field that will bring new opportunities to biotechnology. There is an expectation that synthetic biology will not only enhance knowledge in basic science, but will also have great potential for practical applications. Synthetic biology is still in an early developmental stage in China. We provide here a review of current Chinese research activities in synthetic biology and its different subfields, such as research on genetic circuits, minimal genomes, chemical synthetic biology, protocells and DNA synthesis, using literature reviews and personal communications with Chinese researchers. To meet the increasing demand for a sustainable development, research on genetic circuits to harness biomass is the most pursed research within Chinese researchers. The environmental concerns are driven force of research on the genetic circuits for bioremediation. The research on minimal genomes is carried on identifying the smallest number of genomes needed for engineering minimal cell factories and research on chemical synthetic biology is focused on artificial proteins and expanded genetic code. The research on protocells is more in combination with the research on molecular-scale motors. The research on DNA synthesis and its commercialisation are also reviewed. As for the perspective on potential future Chinese R&D activities, it will be discussed based on the research capacity and governmental policy. PMID:21729747

Biosynthesis of therapeutic natural products using synthetic biology.

PubMed

Awan, Ali R; Shaw, William M; Ellis, Tom

2016-10-01

Natural products are a group of bioactive structurally diverse chemicals produced by microorganisms and plants. These molecules and their derivatives have contributed to over a third of the therapeutic drugs produced in the last century. However, over the last few decades traditional drug discovery pipelines from natural products have become far less productive and far more expensive. One recent development with promise to combat this trend is the application of synthetic biology to therapeutic natural product biosynthesis. Synthetic biology is a young discipline with roots in systems biology, genetic engineering, and metabolic engineering. In this review, we discuss the use of synthetic biology to engineer improved yields of existing therapeutic natural products. We further describe the use of synthetic biology to combine and express natural product biosynthetic genes in unprecedented ways, and how this holds promise for opening up completely new avenues for drug discovery and production. Copyright © 2016 Elsevier B.V. All rights reserved.

Yeast synthetic biology toolbox and applications for biofuel production.

PubMed

Tsai, Ching-Sung; Kwak, Suryang; Turner, Timothy L; Jin, Yong-Su

2015-02-01

Yeasts are efficient biofuel producers with numerous advantages outcompeting bacterial counterparts. While most synthetic biology tools have been developed and customized for bacteria especially for Escherichia coli, yeast synthetic biological tools have been exploited for improving yeast to produce fuels and chemicals from renewable biomass. Here we review the current status of synthetic biological tools and their applications for biofuel production, focusing on the model strain Saccharomyces cerevisiae We describe assembly techniques that have been developed for constructing genes, pathways, and genomes in yeast. Moreover, we discuss synthetic parts for allowing precise control of gene expression at both transcriptional and translational levels. Applications of these synthetic biological approaches have led to identification of effective gene targets that are responsible for desirable traits, such as cellulosic sugar utilization, advanced biofuel production, and enhanced tolerance against toxic products for biofuel production from renewable biomass. Although an array of synthetic biology tools and devices are available, we observed some gaps existing in tool development to achieve industrial utilization. Looking forward, future tool development should focus on industrial cultivation conditions utilizing industrial strains. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Microfluidic Technologies for Synthetic Biology

PubMed Central

Vinuselvi, Parisutham; Park, Seongyong; Kim, Minseok; Park, Jung Min; Kim, Taesung; Lee, Sung Kuk

2011-01-01

Microfluidic technologies have shown powerful abilities for reducing cost, time, and labor, and at the same time, for increasing accuracy, throughput, and performance in the analysis of biological and biochemical samples compared with the conventional, macroscale instruments. Synthetic biology is an emerging field of biology and has drawn much attraction due to its potential to create novel, functional biological parts and systems for special purposes. Since it is believed that the development of synthetic biology can be accelerated through the use of microfluidic technology, in this review work we focus our discussion on the latest microfluidic technologies that can provide unprecedented means in synthetic biology for dynamic profiling of gene expression/regulation with high resolution, highly sensitive on-chip and off-chip detection of metabolites, and whole-cell analysis. PMID:21747695

Proceedings of Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2015

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

Silver, Pamela; Flach, Evan

Synthetic Biology is an emerging discipline that seeks to accelerate the process of engineering biology. As such, the tools are broadly applicable to application areas, including chemicals and biofuels, materials, medicine and agriculture. A characteristic of the field is to look holistically at cellular design, from sensing and genetic circuitry to the manipulation of cellular processes and actuators, to controlling metabolism, to programming multicellular behaviors. Further, the types of cells that are manipulated are broad, from in vitro systems to microbes and fungi to mammalian and plant cells and living animals. Many of the projects in synthetic biology seek tomore » move biochemical functions across organisms. The field is highly interdisciplinary with faculty and students spread across departments that focus on engineering (biological, chemical, electrical, mechanical, civil, computer science) and basic science (biology and systems biology, chemistry, physics). While there have been many one-off workshops and meeting on synthetic biology, the 2014 Synthetic Biology: Engineering, Evolution and Design (SEED) was the first of an annual conference series that serves as a reliable place to pull together the involved disciplines in order to organize and exchange advances in the science and technology in the field. Further, the SEED conferences have a strong focus on industry, with many companies represented and actively participating. A number of these companies have started major efforts in synthetic biology including large companies (e.g., Pfizer, Novartis, Dow, Dupont, BP, Total), smaller companies have recently gone public (e.g., Amyris, Gevo, Intrexon), and many start-ups (e.g., Teslagen, Refactored Materials, Pivot, Genomatica). There are a number of loosely affiliated Synthetic Biology Centers, including ones at MIT, Boston University, UCSD, UCSF, UC-Berkeley, Imperial College, Oxford, and ETH. SEED 2015 will serve as the primary meeting at which international synthetic biology centers and related infrastructure (synthesis/software/foundries) meet to discuss technology, standards, and education. SEED2015 will be the second in an annual series of meeting held to bring researchers from industry and academia in the area of Synthetic Biology. The first SEED conference was highly successful, attracting 285 attendees with varying backgrounds from academia, industry and government. The SEED series provides leadership in the development of the field of synthetic biology and serves to broaden the participants in the field by appealing to broad sectors in industry and providing a means for young investigators and those outside of the field to participate. Further, the series closely integrates with groups such as the SBCC to provide a means by which the synthetic biology community can communicate with policy makers. Further, we will pursue making the meeting the center for the exchange of educational materials as centers for synthetic biology emerge globally. Proceedings will be published each year in the journal ACS Synthetic Biology. After each SEED meeting, surveys are distributed to assess the success of the conference and to help guide changes year-to-year. The diverse application areas further extend the expertise needed from people in areas such as plant biology, agriculture and soil science, environmental science, medicine, and the chemical industry. These areas could have a widespread impact on society in a number of ways. For example, the CRISPR/Cas9 system that serves to immunize bacteria from phage has provided the fundamental chemistry that is used to edit the genomes of diverse organisms, including human stem cells, crop plants, and livestock animals.« less

Synthetic Biology: Tools to Design, Build, and Optimize Cellular Processes

PubMed Central

Young, Eric; Alper, Hal

2010-01-01

The general central dogma frames the emergent properties of life, which make biology both necessary and difficult to engineer. In a process engineering paradigm, each biological process stream and process unit is heavily influenced by regulatory interactions and interactions with the surrounding environment. Synthetic biology is developing the tools and methods that will increase control over these interactions, eventually resulting in an integrative synthetic biology that will allow ground-up cellular optimization. In this review, we attempt to contextualize the areas of synthetic biology into three tiers: (1) the process units and associated streams of the central dogma, (2) the intrinsic regulatory mechanisms, and (3) the extrinsic physical and chemical environment. Efforts at each of these three tiers attempt to control cellular systems and take advantage of emerging tools and approaches. Ultimately, it will be possible to integrate these approaches and realize the vision of integrative synthetic biology when cells are completely rewired for biotechnological goals. This review will highlight progress towards this goal as well as areas requiring further research. PMID:20150964

Collection of biological and non-biological particles by new and used filters made from glass and electrostatically charged synthetic fibers.

PubMed

Raynor, P C; Kim, B G; Ramachandran, G; Strommen, M R; Horns, J H; Streifel, A J

2008-02-01

Synthetic filters made from fibers carrying electrostatic charges and fiberglass filters that do not carry electrostatic charges are both utilized commonly in heating, ventilating, and air-conditioning (HVAC) systems. The pressure drop and efficiency of a bank of fiberglass filters and a bank of electrostatically charged synthetic filters were measured repeatedly for 13 weeks in operating HVAC systems at a hospital. Additionally, the efficiency with which new and used fiberglass and synthetic filters collected culturable biological particles was measured in a test apparatus. Pressure drop measurements adjusted to equivalent flows indicated that the synthetic filters operated with a pressure drop less than half that of the fiberglass filters throughout the test. When measured using total ambient particles, synthetic filter efficiency decreased during the test period for all particle diameters. For particles 0.7-1.0 mum in diameter, efficiency decreased from 92% to 44%. It is hypothesized that this reduction in collection efficiency may be due to charge shielding. Efficiency did not change significantly for the fiberglass filters during the test period. However, when measured using culturable biological particles in the ambient air, efficiency was essentially the same for new filters and filters used for 13 weeks in the hospital for both the synthetic and fiberglass filters. It is hypothesized that the lack of efficiency reduction for culturable particles may be due to their having higher charge than non-biological particles, allowing them to overcome the effects of charge shielding. The type of particles requiring capture may be an important consideration when comparing the relative performance of electrostatically charged synthetic and fiberglass filters. Electrostatically charged synthetic filters with high initial efficiency can frequently replace traditional fiberglass filters with lower efficiency in HVAC systems because properly designed synthetic filters offer less resistance to air flow. Although the efficiency of charged synthetic filters at collecting non-biological particles declined substantially with use, the efficiency of these filters at collecting biological particles remained steady. These findings suggest that the merits of electrostatically charged synthetic HVAC filters relative to fiberglass filters may be more pronounced if collection of biological particles is of primary concern.

Robust synthetic biology design: stochastic game theory approach.

PubMed

Chen, Bor-Sen; Chang, Chia-Hung; Lee, Hsiao-Ching

2009-07-15

Synthetic biology is to engineer artificial biological systems to investigate natural biological phenomena and for a variety of applications. However, the development of synthetic gene networks is still difficult and most newly created gene networks are non-functioning due to uncertain initial conditions and disturbances of extra-cellular environments on the host cell. At present, how to design a robust synthetic gene network to work properly under these uncertain factors is the most important topic of synthetic biology. A robust regulation design is proposed for a stochastic synthetic gene network to achieve the prescribed steady states under these uncertain factors from the minimax regulation perspective. This minimax regulation design problem can be transformed to an equivalent stochastic game problem. Since it is not easy to solve the robust regulation design problem of synthetic gene networks by non-linear stochastic game method directly, the Takagi-Sugeno (T-S) fuzzy model is proposed to approximate the non-linear synthetic gene network via the linear matrix inequality (LMI) technique through the Robust Control Toolbox in Matlab. Finally, an in silico example is given to illustrate the design procedure and to confirm the efficiency and efficacy of the proposed robust gene design method. http://www.ee.nthu.edu.tw/bschen/SyntheticBioDesign_supplement.pdf.

A Converter from the Systems Biology Markup Language to the Synthetic Biology Open Language.

PubMed

Nguyen, Tramy; Roehner, Nicholas; Zundel, Zach; Myers, Chris J

2016-06-17

Standards are important to synthetic biology because they enable exchange and reproducibility of genetic designs. This paper describes a procedure for converting between two standards: the Systems Biology Markup Language (SBML) and the Synthetic Biology Open Language (SBOL). SBML is a standard for behavioral models of biological systems at the molecular level. SBOL describes structural and basic qualitative behavioral aspects of a biological design. Converting SBML to SBOL enables a consistent connection between behavioral and structural information for a biological design. The conversion process described in this paper leverages Systems Biology Ontology (SBO) annotations to enable inference of a designs qualitative function.

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.

Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging.

PubMed

Gilad, Assaf A; Shapiro, Mikhail G

2017-06-01

Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

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.

Chemical synthetic biology: a mini-review.

PubMed

Chiarabelli, Cristiano; Stano, Pasquale; Luisi, Pier Luigi

2013-01-01

Chemical synthetic biology (CSB) is a branch of synthetic biology (SB) oriented toward the synthesis of chemical structures alternative to those present in nature. Whereas SB combines biology and engineering with the aim of synthesizing biological structures or life forms that do not exist in nature - often based on genome manipulation, CSB uses and assembles biological parts, synthetic or not, to create new and alternative structures. A short epistemological note will introduce the theoretical concepts related to these fields, whereas the text will be largely devoted to introduce and comment two main projects of CSB, carried out in our laboratory in the recent years. The "Never Born Biopolymers" project deals with the construction and the screening of RNA and peptide sequences that are not present in nature, whereas the "Minimal Cell" project focuses on the construction of semi-synthetic compartments (usually liposomes) containing the minimal and sufficient number of components to perform the basic function of a biological cell. These two topics are extremely important for both the general understanding of biology in terms of function, organization, and development, and for applied biotechnology.

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.

"Knight in shining armour" or "Frankenstein's creation"? The coverage of synthetic biology in German-language media.

PubMed

Gschmeidler, Brigitte; Seiringer, Alexandra

2012-02-01

Although still a side issue in the German-language media, attention towards synthetic biology has risen clearly during the last years, in line with the first applications being presented. This paper presents findings from a content analysis of synthetic biology coverage in German-language media over the years 2004-2009. In the media, synthetic biology is not clearly separated from gene technology. News value is attributed to established categories such as persons and events. Many metaphors and analogies used in describing gene technology can also be found in the coverage of synthetic biology; however, engineering metaphors are more prominent. In addition, playfulness constitutes an aspect rarely found in genetic engineering coverage. Overall, the picture emerging is ambivalent, which leaves prospects for the further development of public debate ambiguous.

Engineering and control of biological systems: A new way to tackle complex diseases.

PubMed

Menolascina, Filippo; Siciliano, Velia; di Bernardo, Diego

2012-07-16

The ongoing merge between engineering and biology has contributed to the emerging field of synthetic biology. The defining features of this new discipline are abstraction and standardisation of biological parts, decoupling between parts to prevent undesired cross-talking, and the application of quantitative modelling of synthetic genetic circuits in order to guide their design. Most of the efforts in the field of synthetic biology in the last decade have been devoted to the design and development of functional gene circuits in prokaryotes and unicellular eukaryotes. Researchers have used synthetic biology not only to engineer new functions in the cell, but also to build simpler models of endogenous gene regulatory networks to gain knowledge of the "rules" governing their wiring diagram. However, the need for innovative approaches to study and modify complex signalling and regulatory networks in mammalian cells and multicellular organisms has prompted advances of synthetic biology also in these species, thus contributing to develop innovative ways to tackle human diseases. In this work, we will review the latest progress in synthetic biology and the most significant developments achieved so far, both in unicellular and multicellular organisms, with emphasis on human health. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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.

A survey of enabling technologies in synthetic biology

PubMed Central

2013-01-01

Background Realizing constructive applications of synthetic biology requires continued development of enabling technologies as well as policies and practices to ensure these technologies remain accessible for research. Broadly defined, enabling technologies for synthetic biology include any reagent or method that, alone or in combination with associated technologies, provides the means to generate any new research tool or application. Because applications of synthetic biology likely will embody multiple patented inventions, it will be important to create structures for managing intellectual property rights that best promote continued innovation. Monitoring the enabling technologies of synthetic biology will facilitate the systematic investigation of property rights coupled to these technologies and help shape policies and practices that impact the use, regulation, patenting, and licensing of these technologies. Results We conducted a survey among a self-identifying community of practitioners engaged in synthetic biology research to obtain their opinions and experiences with technologies that support the engineering of biological systems. Technologies widely used and considered enabling by survey participants included public and private registries of biological parts, standard methods for physical assembly of DNA constructs, genomic databases, software tools for search, alignment, analysis, and editing of DNA sequences, and commercial services for DNA synthesis and sequencing. Standards and methods supporting measurement, functional composition, and data exchange were less widely used though still considered enabling by a subset of survey participants. Conclusions The set of enabling technologies compiled from this survey provide insight into the many and varied technologies that support innovation in synthetic biology. Many of these technologies are widely accessible for use, either by virtue of being in the public domain or through legal tools such as non-exclusive licensing. Access to some patent protected technologies is less clear and use of these technologies may be subject to restrictions imposed by material transfer agreements or other contract terms. We expect the technologies considered enabling for synthetic biology to change as the field advances. By monitoring the enabling technologies of synthetic biology and addressing the policies and practices that impact their development and use, our hope is that the field will be better able to realize its full potential. PMID:23663447

Informing Biological Design by Integration of Systems and Synthetic Biology

PubMed Central

Smolke, Christina D.; Silver, Pamela A.

2011-01-01

Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the dynamic and complex behavior of biological systems. Here, we examine the synergies between these two fields. PMID:21414477

Synthetic biology and intellectual property rights: six recommendations.

PubMed

Minssen, Timo; Rutz, Berthold; van Zimmeren, Esther

2015-02-01

On 26th November 2013, the Danish Agency for Science, Technology and Innovation organized an expert meeting on "Synthetic Biology & Intellectual Property Rights" in Copenhagen sponsored by the European Research Area Network in Synthetic Biology (ERASynBio). The meeting brought together ten experts from different countries with a variety of professional backgrounds to discuss emerging challenges and opportunities at the interface of synthetic biology and intellectual property rights. The aim of this article is to provide a summary of the major issues and recommendations discussed during the meeting. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enabling plant synthetic biology through genome engineering.

PubMed

Baltes, Nicholas J; Voytas, Daniel F

2015-02-01

Synthetic biology seeks to create new biological systems, including user-designed plants and plant cells. These systems can be employed for a variety of purposes, ranging from producing compounds of industrial or therapeutic value, to reducing crop losses by altering cellular responses to pathogens or climate change. To realize the full potential of plant synthetic biology, techniques are required that provide control over the genetic code - enabling targeted modifications to DNA sequences within living plant cells. Such control is now within reach owing to recent advances in the use of sequence-specific nucleases to precisely engineer genomes. We discuss here the enormous potential provided by genome engineering for plant synthetic biology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthetic biology as red herring.

PubMed

Preston, Beth

2013-12-01

It has become commonplace to say that with the advent of technologies like synthetic biology the line between artifacts and living organisms, policed by metaphysicians since antiquity, is beginning to blur. But that line began to blur 10,000 years ago when plants and animals were first domesticated; and has been thoroughly blurred at least since agriculture became the dominant human subsistence pattern many millennia ago. Synthetic biology is ultimately only a late and unexceptional offshoot of this prehistoric development. From this perspective, then, synthetic biology is a red herring, distracting us from more thorough philosophical consideration of the most truly revolutionary human practice-agriculture. In the first section of this paper I will make this case with regard to ontology, arguing that synthetic biology crosses no ontological lines that were not crossed already in the Neolithic. In the second section I will construct a parallel case with regard to cognition, arguing that synthetic biology as biological engineering represents no cognitive advance over what was required for domestication and the new agricultural subsistence pattern it grounds. In the final section I will make the case with regard to human existence, arguing that synthetic biology, even if wildly successful, is not in a position to cause significant existential change in what it is to be human over and above the massive existential change caused by the transition to agriculture. I conclude that a longer historical perspective casts new light on some important issues in philosophy of technology and environmental philosophy. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Toward Engineering Synthetic Microbial Metabolism

PubMed Central

McArthur, George H.; Fong, Stephen S.

2010-01-01

The generation of well-characterized parts and the formulation of biological design principles in synthetic biology are laying the foundation for more complex and advanced microbial metabolic engineering. Improvements in de novo DNA synthesis and codon-optimization alone are already contributing to the manufacturing of pathway enzymes with improved or novel function. Further development of analytical and computer-aided design tools should accelerate the forward engineering of precisely regulated synthetic pathways by providing a standard framework for the predictable design of biological systems from well-characterized parts. In this review we discuss the current state of synthetic biology within a four-stage framework (design, modeling, synthesis, analysis) and highlight areas requiring further advancement to facilitate true engineering of synthetic microbial metabolism. PMID:20037734

Interactive learning and action: realizing the promise of synthetic biology for global health.

PubMed

Betten, A Wieke; Roelofsen, Anneloes; Broerse, Jacqueline E W

2013-09-01

The emerging field of synthetic biology has the potential to improve global health. For example, synthetic biology could contribute to efforts at vaccine development in a context in which vaccines and immunization have been identified by the international community as being crucial to international development efforts and, in particular, the millennium development goals. However, past experience with innovations shows that realizing a technology's potential can be difficult and complex. To achieve better societal embedding of synthetic biology and to make sure it reaches its potential, science and technology development should be made more inclusive and interactive. Responsible research and innovation is based on the premise that a broad range of stakeholders with different views, needs and ideas should have a voice in the technological development and deployment process. The interactive learning and action (ILA) approach has been developed as a methodology to bring societal stakeholders into a science and technology development process. This paper proposes an ILA in five phases for an international effort, with national case studies, to develop socially robust applications of synthetic biology for global health, based on the example of vaccine development. The design is based on results of a recently initiated ILA project on synthetic biology; results from other interactive initiatives described in the literature; and examples of possible applications of synthetic biology for global health that are currently being developed.

Web-based software tool for constraint-based design specification of synthetic biological systems.

PubMed

Oberortner, Ernst; Densmore, Douglas

2015-06-19

miniEugene provides computational support for solving combinatorial design problems, enabling users to specify and enumerate designs for novel biological systems based on sets of biological constraints. This technical note presents a brief tutorial for biologists and software engineers in the field of synthetic biology on how to use miniEugene. After reading this technical note, users should know which biological constraints are available in miniEugene, understand the syntax and semantics of these constraints, and be able to follow a step-by-step guide to specify the design of a classical synthetic biological system-the genetic toggle switch.1 We also provide links and references to more information on the miniEugene web application and the integration of the miniEugene software library into sophisticated Computer-Aided Design (CAD) tools for synthetic biology ( www.eugenecad.org ).

Mammalian synthetic biology: emerging medical applications

PubMed Central

Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M.; Krams, Rob

2015-01-01

In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON–OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. PMID:25808341

Synthetic Electric Microbial Biosensors

DTIC Science & Technology

2017-06-10

In particular, monitoring of heavy metals in the environment, drinking water, food , and biological fluids is of interest. Conventional techniques...instances of contamination , and the potential for deliberate spills, interest has grown in portable devices for onsite long-term detection using sensor...biosensor systems for the online detection of a range of contaminants . Synthetic Biology and biosensors Synthetic biology has gained much interest

Scientific Opinion on Risk Assessment of Synthetic Biology.

PubMed

Epstein, Michelle M; Vermeire, Theo

2016-08-01

In 2013, three Scientific Committees of the European Commission (EC) drafted Scientific Opinions on synthetic biology that provide an operational definition and address risk assessment methodology, safety aspects, environmental risks, knowledge gaps, and research priorities. These Opinions contribute to the international discussions on the risk governance for synthetic biology developments. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Enzyme and microbial technology for synthesis of bioactive oligosaccharides: an update.

PubMed

Chen, Rachel

2018-04-01

Oligosaccharides, in either free or bound forms, play crucial roles in a wide range of biological processes. Increasing appreciation of their roles in cellular communication, interaction, pathogenesis, and prebiotic functions has stimulated tremendous interests in their synthesis. Pure and structurally defined oligosaccharides are essential for fundamental studies. On the other hand, for those with near term medical and nutraceutical applications, their large-scale synthesis is necessary. Unfortunately, oligosaccharides are notoriously difficult in their synthesis, and their enormous diverse structures leave a vast gap between what have been synthesized in laboratory and those present in various biological systems. While enzymes and microbes are nature's catalysts for oligosaccharides, their effective use is not without challenges. Using examples of galactose-containing oligosaccharides, this review analyzes the pros and cons of these two forms of biocatalysts and provides an updated view on the status of biocatalysis in this important field. Over the past few years, a large number of novel galactosidases were discovered and/or engineered for improved synthesis via transglycosylation. The use of salvage pathway for regeneration of uridine diphosphate (UDP)-galactose has made the use of Leloir glycosyltransferases simpler and more efficient. The recent success of large-scale synthesis of 2' fucosyllactose heralded the power of whole-cell biocatalysis as a scalable technology. While it still lags behind enzyme catalysis in terms of the number of oligosaccharides synthesized, an acceleration in the use of this form of biocatalyst is expected as rapid advances in synthetic biology have made the engineering of whole cell biocatalysts less arduous and less time consuming.

Technical Assessment: Synthetic Biology

DTIC Science & Technology

2015-01-01

to help heal wounds; probiotics that mitigate the effects of stress and enhance mental performance. The same characteristics that make synthetic... probiotics . 5. BW/CW Defense Despite claims about the risks from synthetic biology often inappropriately drowning out discussions of other

Therapeutic synthetic gene networks.

PubMed

Karlsson, Maria; Weber, Wilfried

2012-10-01

The field of synthetic biology is rapidly expanding and has over the past years evolved from the development of simple gene networks to complex treatment-oriented circuits. The reprogramming of cell fate with open-loop or closed-loop synthetic control circuits along with biologically implemented logical functions have fostered applications spanning over a wide range of disciplines, including artificial insemination, personalized medicine and the treatment of cancer and metabolic disorders. In this review we describe several applications of interactive gene networks, a synthetic biology-based approach for future gene therapy, as well as the utilization of synthetic gene circuits as blueprints for the design of stimuli-responsive biohybrid materials. The recent progress in synthetic biology, including the rewiring of biosensing devices with the body's endogenous network as well as novel therapeutic approaches originating from interdisciplinary work, generates numerous opportunities for future biomedical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

Peripheral nerve conduits: technology update

PubMed Central

Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

2014-01-01

Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

Using synthetic biology to make cells tomorrow's test tubes.

PubMed

Garcia, Hernan G; Brewster, Robert C; Phillips, Rob

2016-04-18

The main tenet of physical biology is that biological phenomena can be subject to the same quantitative and predictive understanding that physics has afforded in the context of inanimate matter. However, the inherent complexity of many of these biological processes often leads to the derivation of complex theoretical descriptions containing a plethora of unknown parameters. Such complex descriptions pose a conceptual challenge to the establishment of a solid basis for predictive biology. In this article, we present various exciting examples of how synthetic biology can be used to simplify biological systems and distill these phenomena down to their essential features as a means to enable their theoretical description. Here, synthetic biology goes beyond previous efforts to engineer nature and becomes a tool to bend nature to understand it. We discuss various recent and classic experiments featuring applications of this synthetic approach to the elucidation of problems ranging from bacteriophage infection, to transcriptional regulation in bacteria and in developing embryos, to evolution. In all of these examples, synthetic biology provides the opportunity to turn cells into the equivalent of a test tube, where biological phenomena can be reconstituted and our theoretical understanding put to test with the same ease that these same phenomena can be studied in the in vitro setting.

Towards a behavioral-matching based compilation of synthetic biology functions.

PubMed

Basso-Blandin, Adrien; Delaplace, Franck

2015-09-01

The field of synthetic biology is looking forward engineering framework for safely designing reliable de-novo biological functions. In this undertaking, Computer-Aided-Design (CAD) environments should play a central role for facilitating the design. Although, CAD environment is widely used to engineer artificial systems the application in synthetic biology is still in its infancy. In this article we address the problem of the design of a high level language which at the core of CAD environment. More specifically the Gubs (Genomic Unified Behavioural Specification) language is a specification language used to describe the observations of the expected behaviour. The compiler appropriately selects components such that the observation of the synthetic biological function resulting to their assembly complies to the programmed behaviour.

Defining the Synthetic Biology Supply Chain

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

Frazar, Sarah L.; Hund, Gretchen E.; Bonheyo, George T.

In this article, a team of experts in synthetic biology, data analytics, and national security describe the overall supply chain surrounding synthetic biology. The team analyzes selected interactions within that network to better understand the risks raised by synthetic biology and identifies opportunities for risk mitigation. To introduce the concept, the article will briefly describe how an understanding of supply chains has been important in promoting nuclear nonproliferation objectives. The article concludes by assessing the structure and networks identified in the supply chains to reveal potential opportunities for future biodefense research and development; options for additional information exchange; and meansmore » to interdict, detect, or deter suspicious activity.« less

Synthetic biology advances and applications in the biotechnology industry: a perspective.

PubMed

Katz, Leonard; Chen, Yvonne Y; Gonzalez, Ramon; Peterson, Todd C; Zhao, Huimin; Baltz, Richard H

2018-06-18

Synthetic biology is a logical extension of what has been called recombinant DNA (rDNA) technology or genetic engineering since the 1970s. As rDNA technology has been the driver for the development of a thriving biotechnology industry today, starting with the commercialization of biosynthetic human insulin in the early 1980s, synthetic biology has the potential to take the industry to new heights in the coming years. Synthetic biology advances have been driven by dramatic cost reductions in DNA sequencing and DNA synthesis; by the development of sophisticated tools for genome editing, such as CRISPR/Cas9; and by advances in informatics, computational tools, and infrastructure to facilitate and scale analysis and design. Synthetic biology approaches have already been applied to the metabolic engineering of microorganisms for the production of industrially important chemicals and for the engineering of human cells to treat medical disorders. It also shows great promise to accelerate the discovery and development of novel secondary metabolites from microorganisms through traditional, engineered, and combinatorial biosynthesis. We anticipate that synthetic biology will continue to have broadening impacts on the biotechnology industry to address ongoing issues of human health, world food supply, renewable energy, and industrial chemicals and enzymes.

Varieties of noise: analogical reasoning in synthetic biology.

PubMed

Knuuttila, Tarja; Loettgers, Andrea

2014-12-01

The picture of synthetic biology as a kind of engineering science has largely created the public understanding of this novel field, covering both its promises and risks. In this paper, we will argue that the actual situation is more nuanced and complex. Synthetic biology is a highly interdisciplinary field of research located at the interface of physics, chemistry, biology, and computational science. All of these fields provide concepts, metaphors, mathematical tools, and models, which are typically utilized by synthetic biologists by drawing analogies between the different fields of inquiry. We will study analogical reasoning in synthetic biology through the emergence of the functional meaning of noise, which marks an important shift in how engineering concepts are employed in this field. The notion of noise serves also to highlight the differences between the two branches of synthetic biology: the basic science-oriented branch and the engineering-oriented branch, which differ from each other in the way they draw analogies to various other fields of study. Moreover, we show that fixing the mapping between a source domain and the target domain seems not to be the goal of analogical reasoning in actual scientific practice.

Synthetic biology, metaphors and responsibility.

PubMed

McLeod, Carmen; Nerlich, Brigitte

2017-08-29

Metaphors are not just decorative rhetorical devices that make speech pretty. They are fundamental tools for thinking about the world and acting on the world. The language we use to make a better world matters; words matter; metaphors matter. Words have consequences - ethical, social and legal ones, as well as political and economic ones. They need to be used 'responsibly'. They also need to be studied carefully - this is what we want to do through this editorial and the related thematic collection. In the context of synthetic biology, natural and social scientists have become increasingly interested in metaphors, a wave of interest that we want to exploit and amplify. We want to build on emerging articles and books on synthetic biology, metaphors of life and the ethical and moral implications of such metaphors. This editorial provides a brief introduction to synthetic biology and responsible innovation, as well as a comprehensive review of literature on the social, cultural and ethical impacts of metaphor use in genomics and synthetic biology. Our aim is to stimulate an interdisciplinary and international discussion on the impact that metaphors can have on science, policy and publics in the context of synthetic biology.

Synthetic biology in space: considering the broad societal and ethical implications

NASA Astrophysics Data System (ADS)

Race, Margaret S.; Moses, Jacob; McKay, Christopher; Venkateswaran, Kasthuri J.

2012-02-01

Although the field of synthetic biology is still in its infancy, there are expectations for great advances in the coming decades, both on Earth and potentially in space. Promising applications for long duration space missions include a variety of biologically engineered products and biologically aided processes and technologies, which will undoubtedly be scrutinized for risks and benefits in the broad context of ethical, legal and social realms. By comparing and contrasting features of Earth-based and space-applied synthetic biology, it is possible to identify the likely similarities and differences, and to identify possible challenges ahead for space applications that will require additional research, both in the short and long terms. Using an analytical framework associated with synthetic biology and new technologies on Earth, this paper analyses the kinds of issues and concerns ahead, and identifies those areas where space applications may require additional examination. In general, while Earth- and space-based synthetic biology share many commonalities, space applications have additional challenges such as those raised by space microbiology and environmental factors, legal complications, planetary protection, lack of decision-making infrastructure(s), long duration human missions, terraforming and the possible discovery of extraterrestrial (ET) life. For synthetic biology, the way forward offers many exciting opportunities, but is not without legitimate concerns - for life, environments and society, both on Earth and beyond.

The fusion of biology, computer science, and engineering: towards efficient and successful synthetic biology.

PubMed

Linshiz, Gregory; Goldberg, Alex; Konry, Tania; Hillson, Nathan J

2012-01-01

Synthetic biology is a nascent field that emerged in earnest only around the turn of the millennium. It aims to engineer new biological systems and impart new biological functionality, often through genetic modifications. The design and construction of new biological systems is a complex, multistep process, requiring multidisciplinary collaborative efforts from "fusion" scientists who have formal training in computer science or engineering, as well as hands-on biological expertise. The public has high expectations for synthetic biology and eagerly anticipates the development of solutions to the major challenges facing humanity. This article discusses laboratory practices and the conduct of research in synthetic biology. It argues that the fusion science approach, which integrates biology with computer science and engineering best practices, including standardization, process optimization, computer-aided design and laboratory automation, miniaturization, and systematic management, will increase the predictability and reproducibility of experiments and lead to breakthroughs in the construction of new biological systems. The article also discusses several successful fusion projects, including the development of software tools for DNA construction design automation, recursive DNA construction, and the development of integrated microfluidics systems.

[From synthetic biology to synthetic humankind].

PubMed

Nouvel, Pascal

2015-01-01

In this paper, we propose an historical survey of the expression "synthetic biology" in order to identify its main philosophical components. The result of the analysis is then used to investigate the meaning of the notion of "synthetic man". It is shown that both notions share a common philosophical background that can be summed up by the short but meaningful assertion: "biology is technology". The analysis allows us to distinguish two notions that are often confused in transhumanist literature: the notion of synthetic man and the notion of renewed man. The consequences of this crucial distinction are discussed. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Synthetic analogs of bacterial quorum sensors

DOEpatents

Iyer, Rashi [Los Alamos, NM; Ganguly, Kumkum [Los Alamos, NM; Silks, Louis A [Los Alamos, NM

2011-12-06

Bacterial quorum-sensing molecule analogs having the following structures: ##STR00001## and methods of reducing bacterial pathogenicity, comprising providing a biological system comprising pathogenic bacteria which produce natural quorum-sensing molecule; providing a synthetic bacterial quorum-sensing molecule having the above structures and introducing the synthetic quorum-sensing molecule into the biological system comprising pathogenic bacteria. Further is provided a method of targeted delivery of an antibiotic, comprising providing a synthetic quorum-sensing molecule; chemically linking the synthetic quorum-sensing molecule to an antibiotic to produce a quorum-sensing molecule-antibiotic conjugate; and introducing the conjugate into a biological system comprising pathogenic bacteria susceptible to the antibiotic.

Synthetic analogs of bacterial quorum sensors

DOEpatents

Iyer, Rashi S.; Ganguly, Kumkum; Silks, Louis A.

2013-01-08

Bacterial quorum-sensing molecule analogs having the following structures: ##STR00001## and methods of reducing bacterial pathogenicity, comprising providing a biological system comprising pathogenic bacteria which produce natural quorum-sensing molecule; providing a synthetic bacterial quorum-sensing molecule having the above structures and introducing the synthetic quorum-sensing molecule into the biological system comprising pathogenic bacteria. Further is provided a method of targeted delivery of an antibiotic, comprising providing a synthetic quorum-sensing molecule; chemically linking the synthetic quorum-sensing molecule to an antibiotic to produce a quorum-sensing molecule-antibiotic conjugate; and introducing the conjugate into a biological system comprising pathogenic bacteria susceptible to the antibiotic.

Growing Spaceships?

NASA Technical Reports Server (NTRS)

Robertson, Glen A.

2013-01-01

NASA currently has a program called the Space Synthetic Biology Project. Synthetic Biology or SynBio is the design and construction of new biological functions and systems not found in nature. Four NASA field centers, along with experts from industry and academia, have been partnering on the Space Synthetic Biology Project and are working on new breakthroughs in this increasingly useful pursuit, which is part a science discipline and part engineering. Led by researchers at NASA s Ames Research Center, the team is studying how this powerful new tool can help NASA now and in the future. The project was created to harness biology in reliable, robust, engineered systems to support the agency s exploration and science missions, to improve life on Earth and to help shape NASA's future. The program also is intended to contribute foundational tools to the synthetic biology research community.

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

Informing biological design by integration of systems and synthetic biology.

PubMed

Smolke, Christina D; Silver, Pamela A

2011-03-18

Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the dynamic and complex behavior of biological systems. Here, we examine the synergies between these two fields. Copyright © 2011 Elsevier Inc. All rights reserved.

Prospective Technology Assessment of Synthetic Biology: Fundamental and Propaedeutic Reflections in Order to Enable an Early Assessment.

PubMed

Schmidt, Jan Cornelius

2016-08-01

Synthetic biology is regarded as one of the key technosciences of the future. The goal of this paper is to present some fundamental considerations to enable procedures of a technology assessment (TA) of synthetic biology. To accomplish such an early "upstream" assessment of a not yet fully developed technology, a special type of TA will be considered: Prospective TA (ProTA). At the center of ProTA are the analysis and the framing of "synthetic biology," including a characterization and assessment of the technological core. The thesis is that if there is any differentia specifica giving substance to the umbrella term "synthetic biology," it is the idea of harnessing self-organization for engineering purposes. To underline that we are likely experiencing an epochal break in the ontology of technoscientific systems, this new type of technology is called "late-modern technology." -I start this paper by analyzing the three most common visions of synthetic biology. Then I argue that one particular vision deserves more attention because it underlies the others: the vision of self-organization. I discuss the inherent limits of this new type of late-modern technology in the attempt to control and monitor possible risk issues. I refer to Hans Jonas' ethics and his early anticipation of the risks of a novel type of technology. I end by drawing conclusions for the approach of ProTA towards an early societal shaping of synthetic biology.

Synthetic biology era: Improving antibiotic's world.

PubMed

Guzmán-Trampe, Silvia; Ceapa, Corina D; Manzo-Ruiz, Monserrat; Sánchez, Sergio

2017-06-15

The emergence of antibiotic-resistant pathogen microorganisms is problematic in the context of the current spectrum of available medication. The poor specificity and the high toxicity of some available molecules have made imperative the search for new strategies to improve the specificity and to pursue the discovery of novel compounds with increased bioactivity. Using living cells as platforms, synthetic biology has counteracted this problem by offering novel pathways to create synthetic systems with improved and desired functions. Among many other biotechnological approaches, the advances in synthetic biology have made it possible to design and construct novel biological systems in order to look for new drugs with increased bioactivity. Advancements have also been made in the redesigning of RNA and DNA molecules in order to engineer antibiotic clusters for antibiotic overexpression. As for the production of these antibacterial compounds, yeasts and filamentous fungi as well as gene therapy are utilized to enhance protein solubility. Specific delivery is achieved by creating chimeras using plant genes into bacterial hosts. Some of these synthetic systems are currently in clinical trials, proving the proficiency of synthetic biology in terms of both pharmacological activities as well as an increase in the biosafety of treatments. It is possible that we may just be seeing the tip of the iceberg, and synthetic biology applications will overpass expectations beyond our present knowledge. Copyright © 2017. Published by Elsevier Inc.

TinkerCell: modular CAD tool for synthetic biology.

PubMed

Chandran, Deepak; Bergmann, Frank T; Sauro, Herbert M

2009-10-29

Synthetic biology brings together concepts and techniques from engineering and biology. In this field, computer-aided design (CAD) is necessary in order to bridge the gap between computational modeling and biological data. Using a CAD application, it would be possible to construct models using available biological "parts" and directly generate the DNA sequence that represents the model, thus increasing the efficiency of design and construction of synthetic networks. An application named TinkerCell has been developed in order to serve as a CAD tool for synthetic biology. TinkerCell is a visual modeling tool that supports a hierarchy of biological parts. Each part in this hierarchy consists of a set of attributes that define the part, such as sequence or rate constants. Models that are constructed using these parts can be analyzed using various third-party C and Python programs that are hosted by TinkerCell via an extensive C and Python application programming interface (API). TinkerCell supports the notion of a module, which are networks with interfaces. Such modules can be connected to each other, forming larger modular networks. TinkerCell is a free and open-source project under the Berkeley Software Distribution license. Downloads, documentation, and tutorials are available at http://www.tinkercell.com. An ideal CAD application for engineering biological systems would provide features such as: building and simulating networks, analyzing robustness of networks, and searching databases for components that meet the design criteria. At the current state of synthetic biology, there are no established methods for measuring robustness or identifying components that fit a design. The same is true for databases of biological parts. TinkerCell's flexible modeling framework allows it to cope with changes in the field. Such changes may involve the way parts are characterized or the way synthetic networks are modeled and analyzed computationally. TinkerCell can readily accept third-party algorithms, allowing it to serve as a platform for testing different methods relevant to synthetic biology.

TinkerCell: modular CAD tool for synthetic biology

PubMed Central

Chandran, Deepak; Bergmann, Frank T; Sauro, Herbert M

2009-01-01

Background Synthetic biology brings together concepts and techniques from engineering and biology. In this field, computer-aided design (CAD) is necessary in order to bridge the gap between computational modeling and biological data. Using a CAD application, it would be possible to construct models using available biological "parts" and directly generate the DNA sequence that represents the model, thus increasing the efficiency of design and construction of synthetic networks. Results An application named TinkerCell has been developed in order to serve as a CAD tool for synthetic biology. TinkerCell is a visual modeling tool that supports a hierarchy of biological parts. Each part in this hierarchy consists of a set of attributes that define the part, such as sequence or rate constants. Models that are constructed using these parts can be analyzed using various third-party C and Python programs that are hosted by TinkerCell via an extensive C and Python application programming interface (API). TinkerCell supports the notion of a module, which are networks with interfaces. Such modules can be connected to each other, forming larger modular networks. TinkerCell is a free and open-source project under the Berkeley Software Distribution license. Downloads, documentation, and tutorials are available at . Conclusion An ideal CAD application for engineering biological systems would provide features such as: building and simulating networks, analyzing robustness of networks, and searching databases for components that meet the design criteria. At the current state of synthetic biology, there are no established methods for measuring robustness or identifying components that fit a design. The same is true for databases of biological parts. TinkerCell's flexible modeling framework allows it to cope with changes in the field. Such changes may involve the way parts are characterized or the way synthetic networks are modeled and analyzed computationally. TinkerCell can readily accept third-party algorithms, allowing it to serve as a platform for testing different methods relevant to synthetic biology. PMID:19874625

Integrating biological redesign: where synthetic biology came from and where it needs to go.

PubMed

Way, Jeffrey C; Collins, James J; Keasling, Jay D; Silver, Pamela A

2014-03-27

Synthetic biology seeks to extend approaches from engineering and computation to redesign of biology, with goals such as generating new chemicals, improving human health, and addressing environmental issues. Early on, several guiding principles of synthetic biology were articulated, including design according to specification, separation of design from fabrication, use of standardized biological parts and organisms, and abstraction. We review the utility of these principles over the past decade in light of the field's accomplishments in building complex systems based on microbial transcription and metabolism and describe the progress in mammalian cell engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

The path to next generation biofuels: successes and challenges in the era of synthetic biology

PubMed Central

2010-01-01

Volatility of oil prices along with major concerns about climate change, oil supply security and depleting reserves have sparked renewed interest in the production of fuels from renewable resources. Recent advances in synthetic biology provide new tools for metabolic engineers to direct their strategies and construct optimal biocatalysts for the sustainable production of biofuels. Metabolic engineering and synthetic biology efforts entailing the engineering of native and de novo pathways for conversion of biomass constituents to short-chain alcohols and advanced biofuels are herewith reviewed. In the foreseeable future, formal integration of functional genomics and systems biology with synthetic biology and metabolic engineering will undoubtedly support the discovery, characterization, and engineering of new metabolic routes and more efficient microbial systems for the production of biofuels. PMID:20089184

Terminator Operon Reporter: combining a transcription termination switch with reporter technology for improved gene synthesis and synthetic biology applications.

PubMed

Zampini, Massimiliano; Mur, Luis A J; Rees Stevens, Pauline; Pachebat, Justin A; Newbold, C James; Hayes, Finbarr; Kingston-Smith, Alison

2016-05-25

Synthetic biology is characterized by the development of novel and powerful DNA fabrication methods and by the application of engineering principles to biology. The current study describes Terminator Operon Reporter (TOR), a new gene assembly technology based on the conditional activation of a reporter gene in response to sequence errors occurring at the assembly stage of the synthetic element. These errors are monitored by a transcription terminator that is placed between the synthetic gene and reporter gene. Switching of this terminator between active and inactive states dictates the transcription status of the downstream reporter gene to provide a rapid and facile readout of the accuracy of synthetic assembly. Designed specifically and uniquely for the synthesis of protein coding genes in bacteria, TOR allows the rapid and cost-effective fabrication of synthetic constructs by employing oligonucleotides at the most basic purification level (desalted) and without the need for costly and time-consuming post-synthesis correction methods. Thus, TOR streamlines gene assembly approaches, which are central to the future development of synthetic biology.

Queueing-Based Synchronization and Entrainment for Synthetic Gene Oscillators

NASA Astrophysics Data System (ADS)

Mather, William; Butzin, Nicholas; Hochendoner, Philip; Ogle, Curtis

Synthetic gene oscillators have been a major focus of synthetic biology research since the beginning of the field 15 years ago. They have proven to be useful both for biotechnological applications as well as a testing ground to significantly develop our understanding of the design principles behind synthetic and native gene oscillators. In particular, the principles governing synchronization and entrainment of biological oscillators have been explored using a synthetic biology approach. Our work combines experimental and theoretical approaches to specifically investigate how a bottleneck for protein degradation, which is present in most if not all existing synthetic oscillators, can be leveraged to robustly synchronize and entrain biological oscillators. We use both the terminology and mathematical tools of queueing theory to intuitively explain the role of this bottleneck in both synchronization and entrainment, which extends prior work demonstrating the usefulness of queueing theory in synthetic and native gene circuits. We conclude with an investigation of how synchronization and entrainment may be sensitive to the presence of multiple proteolytic pathways in a cell that couple weakly through crosstalk. This work was supported by NSF Grant #1330180.

Synthetic Biology and Biosecurity: Challenging the “Myths”

PubMed Central

Jefferson, Catherine; Lentzos, Filippa; Marris, Claire

2014-01-01

Synthetic biology, a field that aims to “make biology easier to engineer,” is routinely described as leading to an increase in the “dual-use” threat, i.e., the potential for the same scientific research to be “used” for peaceful purposes or “misused” for warfare or terrorism. Fears have been expressed that the “de-skilling” of biology, combined with online access to the genomic DNA sequences of pathogenic organisms and the reduction in price for DNA synthesis, will make biology increasingly accessible to people operating outside well-equipped professional research laboratories, including people with malevolent intentions. The emergence of do-it-yourself (DIY) biology communities and of the student iGEM competition has come to epitomize this supposed trend toward greater ease of access and the associated potential threat from rogue actors. In this article, we identify five “myths” that permeate discussions about synthetic biology and biosecurity, and argue that they embody misleading assumptions about both synthetic biology and bioterrorism. We demonstrate how these myths are challenged by more realistic understandings of the scientific research currently being conducted in both professional and DIY laboratories, and by an analysis of historical cases of bioterrorism. We show that the importance of tacit knowledge is commonly overlooked in the dominant narrative: the focus is on access to biological materials and digital information, rather than on human practices and institutional dimensions. As a result, public discourse on synthetic biology and biosecurity tends to portray speculative scenarios about the future as realities in the present or the near future, when this is not warranted. We suggest that these “myths” play an important role in defining synthetic biology as a “promissory” field of research and as an “emerging technology” in need of governance. PMID:25191649

Synthetic biology and biosecurity: challenging the "myths".

PubMed

Jefferson, Catherine; Lentzos, Filippa; Marris, Claire

2014-01-01

Synthetic biology, a field that aims to "make biology easier to engineer," is routinely described as leading to an increase in the "dual-use" threat, i.e., the potential for the same scientific research to be "used" for peaceful purposes or "misused" for warfare or terrorism. Fears have been expressed that the "de-skilling" of biology, combined with online access to the genomic DNA sequences of pathogenic organisms and the reduction in price for DNA synthesis, will make biology increasingly accessible to people operating outside well-equipped professional research laboratories, including people with malevolent intentions. The emergence of do-it-yourself (DIY) biology communities and of the student iGEM competition has come to epitomize this supposed trend toward greater ease of access and the associated potential threat from rogue actors. In this article, we identify five "myths" that permeate discussions about synthetic biology and biosecurity, and argue that they embody misleading assumptions about both synthetic biology and bioterrorism. We demonstrate how these myths are challenged by more realistic understandings of the scientific research currently being conducted in both professional and DIY laboratories, and by an analysis of historical cases of bioterrorism. We show that the importance of tacit knowledge is commonly overlooked in the dominant narrative: the focus is on access to biological materials and digital information, rather than on human practices and institutional dimensions. As a result, public discourse on synthetic biology and biosecurity tends to portray speculative scenarios about the future as realities in the present or the near future, when this is not warranted. We suggest that these "myths" play an important role in defining synthetic biology as a "promissory" field of research and as an "emerging technology" in need of governance.

CSBB: synthetic biology research at Newcastle University.

PubMed

Goñi-Moreno, Angel; Wipat, Anil; Krasnogor, Natalio

2017-06-15

The Centre for Synthetic Biology and the Bioeconomy (CSBB) brings together a far-reaching multidisciplinary community across all Newcastle University's faculties - Medical Sciences, Science, Agriculture and Engineering, and Humanities, Arts and Social Sciences. The CSBB focuses on many different areas of Synthetic Biology, including bioprocessing, computational design and in vivo computation, as well as improving understanding of basic molecular machinery. Such breadth is supported by major national and international research funding, a range of industrial partners in the North East of England and beyond, as well as a large number of doctoral and post-doctoral researchers. The CSBB trains the next generation of scientists through a 1-year MSc in Synthetic Biology. © 2017 The Author(s).

Communicating Synthetic Biology: from the lab via the media to the broader public.

PubMed

Kronberger, Nicole; Holtz, Peter; Kerbe, Wolfgang; Strasser, Ewald; Wagner, Wolfgang

2009-12-01

We present insights from a study on communicating Synthetic Biology conducted in 2008. Scientists were invited to write press releases on their work; the resulting texts were passed on to four journalists from major Austrian newspapers and magazines. The journalists in turn wrote articles that were used as stimulus material for eight group discussions with select members of the Austrian public. The results show that, from the lab via the media to the general public, communication is characterized by two important tendencies: first, communication becomes increasingly focused on concrete applications of Synthetic Biology; and second, biotechnology represents an important benchmark against which Synthetic Biology is being evaluated.

Mammalian synthetic biology: emerging medical applications.

PubMed

Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

2015-05-06

In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

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.

[Impact of synthetic biology on patent law in view of of European jurisprudence].

PubMed

Bernardo Alvarez, María Angela

2014-01-01

The roots of synthetic biology--the redesign of biological molecules, structures and organisms--can be traced to the research developed by Jacques L. Monod and François Jacob in 1961. This field has undergone significant growth in the past ten years and its emergence has raised the question of whether the patent system is suitable to protect inventions in emergent areas as synthetic biology. The article will analyze the numerous scientific, socio-economic, ethical and legal challenges faced by synthetic biology, introducing the European Patent Law related to biotechnology as the minimum common framework and considering if more changes are needed to adequately protect the inventor rights, while taking into account the arrival of a new research culture, characterized by embracing open-innovation and open-source initiatives. The discussion will review some biotechnological patent law cases and summarize questions as whether isolated molecules of DNA are eligible for patent or the patentability of living matter, under the terms of Directive 98/44/EC. The article will finally consider the impact of synthetic biology on the European patent system.

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

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.

Generating Systems Biology Markup Language Models from the Synthetic Biology Open Language.

PubMed

Roehner, Nicholas; Zhang, Zhen; Nguyen, Tramy; Myers, Chris J

2015-08-21

In the context of synthetic biology, model generation is the automated process of constructing biochemical models based on genetic designs. This paper discusses the use cases for model generation in genetic design automation (GDA) software tools and introduces the foundational concepts of standards and model annotation that make this process useful. Finally, this paper presents an implementation of model generation in the GDA software tool iBioSim and provides an example of generating a Systems Biology Markup Language (SBML) model from a design of a 4-input AND sensor written in the Synthetic Biology Open Language (SBOL).

Landauer in the Age of Synthetic Biology: Energy Consumption and Information Processing in Biochemical Networks

NASA Astrophysics Data System (ADS)

Mehta, Pankaj; Lang, Alex H.; Schwab, David J.

2016-03-01

A central goal of synthetic biology is to design sophisticated synthetic cellular circuits that can perform complex computations and information processing tasks in response to specific inputs. The tremendous advances in our ability to understand and manipulate cellular information processing networks raises several fundamental physics questions: How do the molecular components of cellular circuits exploit energy consumption to improve information processing? Can one utilize ideas from thermodynamics to improve the design of synthetic cellular circuits and modules? Here, we summarize recent theoretical work addressing these questions. Energy consumption in cellular circuits serves five basic purposes: (1) increasing specificity, (2) manipulating dynamics, (3) reducing variability, (4) amplifying signal, and (5) erasing memory. We demonstrate these ideas using several simple examples and discuss the implications of these theoretical ideas for the emerging field of synthetic biology. We conclude by discussing how it may be possible to overcome these limitations using "post-translational" synthetic biology that exploits reversible protein modification.

WISB: Warwick Integrative Synthetic Biology Centre

PubMed Central

McCarthy, John

2016-01-01

Synthetic biology promises to create high-impact solutions to challenges in the areas of biotechnology, human/animal health, the environment, energy, materials and food security. Equally, synthetic biologists create tools and strategies that have the potential to help us answer important fundamental questions in biology. Warwick Integrative Synthetic Biology (WISB) pursues both of these mutually complementary ‘build to apply’ and ‘build to understand’ approaches. This is reflected in our research structure, in which a core theme on predictive biosystems engineering develops underpinning understanding as well as next-generation experimental/theoretical tools, and these are then incorporated into three applied themes in which we engineer biosynthetic pathways, microbial communities and microbial effector systems in plants. WISB takes a comprehensive approach to training, education and outreach. For example, WISB is a partner in the EPSRC/BBSRC-funded U.K. Doctoral Training Centre in synthetic biology, we have developed a new undergraduate module in the subject, and we have established five WISB Research Career Development Fellowships to support young group leaders. Research in Ethical, Legal and Societal Aspects (ELSA) of synthetic biology is embedded in our centre activities. WISB has been highly proactive in building an international research and training network that includes partners in Barcelona, Boston, Copenhagen, Madrid, Marburg, São Paulo, Tartu and Valencia. PMID:27284024

WISB: Warwick Integrative Synthetic Biology Centre.

PubMed

McCarthy, John

2016-06-15

Synthetic biology promises to create high-impact solutions to challenges in the areas of biotechnology, human/animal health, the environment, energy, materials and food security. Equally, synthetic biologists create tools and strategies that have the potential to help us answer important fundamental questions in biology. Warwick Integrative Synthetic Biology (WISB) pursues both of these mutually complementary 'build to apply' and 'build to understand' approaches. This is reflected in our research structure, in which a core theme on predictive biosystems engineering develops underpinning understanding as well as next-generation experimental/theoretical tools, and these are then incorporated into three applied themes in which we engineer biosynthetic pathways, microbial communities and microbial effector systems in plants. WISB takes a comprehensive approach to training, education and outreach. For example, WISB is a partner in the EPSRC/BBSRC-funded U.K. Doctoral Training Centre in synthetic biology, we have developed a new undergraduate module in the subject, and we have established five WISB Research Career Development Fellowships to support young group leaders. Research in Ethical, Legal and Societal Aspects (ELSA) of synthetic biology is embedded in our centre activities. WISB has been highly proactive in building an international research and training network that includes partners in Barcelona, Boston, Copenhagen, Madrid, Marburg, São Paulo, Tartu and Valencia. © 2016 The Author(s).

pClone: Synthetic Biology Tool Makes Promoter Research Accessible to Beginning Biology Students

ERIC Educational Resources Information Center

Campbell, A. Malcolm; Eckdahl, Todd; Cronk, Brian; Andresen, Corinne; Frederick, Paul; Huckuntod, Samantha; Shinneman, Claire; Wacker, Annie; Yuan, Jason

2014-01-01

The "Vision and Change" report recommended genuine research experiences for undergraduate biology students. Authentic research improves science education, increases the number of scientifically literate citizens, and encourages students to pursue research. Synthetic biology is well suited for undergraduate research and is a growing area…

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

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.

Synthetic biology: evolution or revolution? A co-founder's perspective.

PubMed

Gardner, Timothy S; Hawkins, Kristy

2013-12-01

In this article, we relate the story of Synthetic Biology's birth, from the perspective of a co-founder, and consider its original premise--that standardization and abstraction of biological components will unlock the full potential of biological engineering. The standardization ideas of Synthetic Biology emerged in the late 1990s from a convergence of research on cellular computing, and were motivated by an array of applications from tissue regeneration to bio-sensing to mathematical programming. As the definition of Synthetic Biology has grown to be synonymous with Biological Engineering and Biotechnology, the field has lost sight of the fact that its founding premise has not yet been validated. While the value of standardization has been proven in many other engineering disciplines, none of them involve self-replicating systems. The engineering of self-replicating systems will likely benefit from standardization, and also by embracing the forces of evolution that inexorably shape such systems. Copyright © 2013 Elsevier Ltd. All rights reserved.

End-to-end automated microfluidic platform for synthetic biology: from design to functional analysis

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

Linshiz, Gregory; Jensen, Erik; Stawski, Nina

Synthetic biology aims to engineer biological systems for desired behaviors. The construction of these systems can be complex, often requiring genetic reprogramming, extensive de novo DNA synthesis, and functional screening. Here, we present a programmable, multipurpose microfluidic platform and associated software and apply the platform to major steps of the synthetic biology research cycle: design, construction, testing, and analysis. We show the platform’s capabilities for multiple automated DNA assembly methods, including a new method for Isothermal Hierarchical DNA Construction, and for Escherichia coli and Saccharomyces cerevisiae transformation. The platform enables the automated control of cellular growth, gene expression induction, andmore » proteogenic and metabolic output analysis. Finally, taken together, we demonstrate the microfluidic platform’s potential to provide end-to-end solutions for synthetic biology research, from design to functional analysis.« less

End-to-end automated microfluidic platform for synthetic biology: from design to functional analysis

DOE PAGES

Linshiz, Gregory; Jensen, Erik; Stawski, Nina; ...

2016-02-02

Synthetic biology aims to engineer biological systems for desired behaviors. The construction of these systems can be complex, often requiring genetic reprogramming, extensive de novo DNA synthesis, and functional screening. Here, we present a programmable, multipurpose microfluidic platform and associated software and apply the platform to major steps of the synthetic biology research cycle: design, construction, testing, and analysis. We show the platform’s capabilities for multiple automated DNA assembly methods, including a new method for Isothermal Hierarchical DNA Construction, and for Escherichia coli and Saccharomyces cerevisiae transformation. The platform enables the automated control of cellular growth, gene expression induction, andmore » proteogenic and metabolic output analysis. Finally, taken together, we demonstrate the microfluidic platform’s potential to provide end-to-end solutions for synthetic biology research, from design to functional analysis.« less

Nature versus design: synthetic biology or how to build a biological non-machine.

PubMed

Porcar, M; Peretó, J

2016-04-18

The engineering ideal of synthetic biology presupposes that organisms are composed of standard, interchangeable parts with a predictive behaviour. In one word, organisms are literally recognized as machines. Yet living objects are the result of evolutionary processes without any purposiveness, not of a design by external agents. Biological components show massive overlapping and functional degeneracy, standard-free complexity, intrinsic variation and context dependent performances. However, although organisms are not full-fledged machines, synthetic biologists may still be eager for machine-like behaviours from artificially modified biosystems.

To be or not IP? Exploring limits within patent law for the constitutionalization of intellectual property rights and the governance of synthetic biology in human health.

PubMed

Schneider, Ingrid

2012-01-01

The article explores limits within patent law for the constitutionalization of Intellectual Property Rights and the governance of synthetic biology in human health. To this end, it starts by explaining the inherent rationales of two fundamental limits within European patent law, namely (1) the boundary between discovery and invention (Art. 52 EPC); (2) the ordre public and public policy clause (Art. 53 (a) EPC). Both these exclusions from patent eligibility bear a normative function but rely on opposing inherent logics, functions, and regulatory aims. While in the first type of logics, "enabling access for all" is the guiding principle, in the second, converse logics, no one should have access to the technological knowledge in question. The second part contends that decisions on whether and how to grant patents in synthetic biology are not independent from institutional frameworks: The arena in which synthetic biology patenting will be dealt with will be decisive for whether and how boundaries will be deployed. From a political science perspective, the administrative, legislative and judicial arena can be distinguished. If synthetic biology will be negotiated in the legislative arena, in particular in the European Parliament, the probabilities will be higher that either the discovery clause or the ordre public clause will be applied. In contrast, patent offices and courts have, at least in the past decades, employed a narrow interpretation of these absolute exemptions from patentability and hardly ever used them. The third part asserts that metaphoric framing of synthetic biology is another crucial factor for patentability questions. Semantic framing may relate to the articulation and mobilization of consent or dissent, and thus public acceptance of synthetic biology. Whether applications of synthetic biology are conceived as "natural" or "synthetic" DNA may have an influence on whether patenting might become contested as "patenting life" or accepted as novel, and also on passing the inventive step and industrial application tests. Proceeding in such a manner can be regarded as "upstreaming" ethics, anticipatory impact assessment, and policy analysis in the biosciences and as a tool for constitutionalizing intellectual property rights.

News: Synthetic biology leading to specialty chemicals

EPA Science Inventory

Synthetic biology can combine the disciplines of biology, engineering, and chemistry productively to form molecules of great scientific and commercial value. Recent advances in the new field are explored for their connection to new tools that have been used to elucidate productio...

Engineering for the 21st century: synthetic biology.

PubMed

Munnelly, Kevin

2013-05-17

For years, scientists have hoped that biology would find its engineering counterpart--a series of principles that could be used as reliably as chemical engineering is for chemistry. Thanks to major advances in synthetic biology, those hopes may soon be realized.

Mimicking/extracting structure and functions of natural products: synthetic approaches that address unexplored needs in chemical biology.

PubMed

Hirai, Go

2015-04-01

Natural products are often attractive and challenging targets for synthetic chemists, and many have interesting biological activities. However, synthetic chemists need to be more than simply suppliers of compounds to biologists. Therefore, we have been seeking ways to actively apply organic synthetic methods to chemical biology studies of natural products and their activities. In this personal review, I would like to introduce our work on the development of new biologically active compounds inspired by, or extracted from, the structures of natural products, focusing on enhancement of functional activity and specificity and overcoming various drawbacks of the parent natural products. Copyright © 2014 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biological and chemical weapons of mass destruction: updated clinical therapeutic countermeasures since 2003.

PubMed

Pettineo, Christopher; Aitchison, Robert; Leikin, Scott M; Vogel, Stephen N; Leikin, Jerrold B

2009-01-01

The objective of this article is to provide updated treatment options for bioterrorism agents. This updated synopsis includes recent clinical cases and treatment recommendations that have arisen in the last 5 years. The decontamination, treatment, and disposition of these biologic and chemical agents are presented alphabetically by agent type: biologic, chemical, and radiologic/nuclear. The information provided outlines only new treatment options since 2003.

Automatic design of synthetic gene circuits through mixed integer non-linear programming.

PubMed

Huynh, Linh; Kececioglu, John; Köppe, Matthias; Tagkopoulos, Ilias

2012-01-01

Automatic design of synthetic gene circuits poses a significant challenge to synthetic biology, primarily due to the complexity of biological systems, and the lack of rigorous optimization methods that can cope with the combinatorial explosion as the number of biological parts increases. Current optimization methods for synthetic gene design rely on heuristic algorithms that are usually not deterministic, deliver sub-optimal solutions, and provide no guaranties on convergence or error bounds. Here, we introduce an optimization framework for the problem of part selection in synthetic gene circuits that is based on mixed integer non-linear programming (MINLP), which is a deterministic method that finds the globally optimal solution and guarantees convergence in finite time. Given a synthetic gene circuit, a library of characterized parts, and user-defined constraints, our method can find the optimal selection of parts that satisfy the constraints and best approximates the objective function given by the user. We evaluated the proposed method in the design of three synthetic circuits (a toggle switch, a transcriptional cascade, and a band detector), with both experimentally constructed and synthetic promoter libraries. Scalability and robustness analysis shows that the proposed framework scales well with the library size and the solution space. The work described here is a step towards a unifying, realistic framework for the automated design of biological circuits.

Synthetic biology: insights into biological computation.

PubMed

Manzoni, Romilde; Urrios, Arturo; Velazquez-Garcia, Silvia; de Nadal, Eulàlia; Posas, Francesc

2016-04-18

Organisms have evolved a broad array of complex signaling mechanisms that allow them to survive in a wide range of environmental conditions. They are able to sense external inputs and produce an output response by computing the information. Synthetic biology attempts to rationally engineer biological systems in order to perform desired functions. Our increasing understanding of biological systems guides this rational design, while the huge background in electronics for building circuits defines the methodology. In this context, biocomputation is the branch of synthetic biology aimed at implementing artificial computational devices using engineered biological motifs as building blocks. Biocomputational devices are defined as biological systems that are able to integrate inputs and return outputs following pre-determined rules. Over the last decade the number of available synthetic engineered devices has increased exponentially; simple and complex circuits have been built in bacteria, yeast and mammalian cells. These devices can manage and store information, take decisions based on past and present inputs, and even convert a transient signal into a sustained response. The field is experiencing a fast growth and every day it is easier to implement more complex biological functions. This is mainly due to advances in in vitro DNA synthesis, new genome editing tools, novel molecular cloning techniques, continuously growing part libraries as well as other technological advances. This allows that digital computation can now be engineered and implemented in biological systems. Simple logic gates can be implemented and connected to perform novel desired functions or to better understand and redesign biological processes. Synthetic biological digital circuits could lead to new therapeutic approaches, as well as new and efficient ways to produce complex molecules such as antibiotics, bioplastics or biofuels. Biological computation not only provides possible biomedical and biotechnological applications, but also affords a greater understanding of biological systems.

SEED Servers: High-Performance Access to the SEED Genomes, Annotations, and Metabolic Models

PubMed Central

Aziz, Ramy K.; Devoid, Scott; Disz, Terrence; Edwards, Robert A.; Henry, Christopher S.; Olsen, Gary J.; Olson, Robert; Overbeek, Ross; Parrello, Bruce; Pusch, Gordon D.; Stevens, Rick L.; Vonstein, Veronika; Xia, Fangfang

2012-01-01

The remarkable advance in sequencing technology and the rising interest in medical and environmental microbiology, biotechnology, and synthetic biology resulted in a deluge of published microbial genomes. Yet, genome annotation, comparison, and modeling remain a major bottleneck to the translation of sequence information into biological knowledge, hence computational analysis tools are continuously being developed for rapid genome annotation and interpretation. Among the earliest, most comprehensive resources for prokaryotic genome analysis, the SEED project, initiated in 2003 as an integration of genomic data and analysis tools, now contains >5,000 complete genomes, a constantly updated set of curated annotations embodied in a large and growing collection of encoded subsystems, a derived set of protein families, and hundreds of genome-scale metabolic models. Until recently, however, maintaining current copies of the SEED code and data at remote locations has been a pressing issue. To allow high-performance remote access to the SEED database, we developed the SEED Servers (http://www.theseed.org/servers): four network-based servers intended to expose the data in the underlying relational database, support basic annotation services, offer programmatic access to the capabilities of the RAST annotation server, and provide access to a growing collection of metabolic models that support flux balance analysis. The SEED servers offer open access to regularly updated data, the ability to annotate prokaryotic genomes, the ability to create metabolic reconstructions and detailed models of metabolism, and access to hundreds of existing metabolic models. This work offers and supports a framework upon which other groups can build independent research efforts. Large integrations of genomic data represent one of the major intellectual resources driving research in biology, and programmatic access to the SEED data will provide significant utility to a broad collection of potential users. PMID:23110173

Nonlinear dimensionality reduction methods for synthetic biology biobricks' visualization.

PubMed

Yang, Jiaoyun; Wang, Haipeng; Ding, Huitong; An, Ning; Alterovitz, Gil

2017-01-19

Visualizing data by dimensionality reduction is an important strategy in Bioinformatics, which could help to discover hidden data properties and detect data quality issues, e.g. data noise, inappropriately labeled data, etc. As crowdsourcing-based synthetic biology databases face similar data quality issues, we propose to visualize biobricks to tackle them. However, existing dimensionality reduction methods could not be directly applied on biobricks datasets. Hereby, we use normalized edit distance to enhance dimensionality reduction methods, including Isomap and Laplacian Eigenmaps. By extracting biobricks from synthetic biology database Registry of Standard Biological Parts, six combinations of various types of biobricks are tested. The visualization graphs illustrate discriminated biobricks and inappropriately labeled biobricks. Clustering algorithm K-means is adopted to quantify the reduction results. The average clustering accuracy for Isomap and Laplacian Eigenmaps are 0.857 and 0.844, respectively. Besides, Laplacian Eigenmaps is 5 times faster than Isomap, and its visualization graph is more concentrated to discriminate biobricks. By combining normalized edit distance with Isomap and Laplacian Eigenmaps, synthetic biology biobircks are successfully visualized in two dimensional space. Various types of biobricks could be discriminated and inappropriately labeled biobricks could be determined, which could help to assess crowdsourcing-based synthetic biology databases' quality, and make biobricks selection.

From Extremophiles to Star Trek, The Use of Synthetic Biology in Astrobiology

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.; Fujishima, Kosuke; Lima, Ivan Paulino; Gentry, Diana; Phan, Samson; Navarette, Jesica; Palmer, Jesse; Burnier, Andre

2012-01-01

Synthetic biology – the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes – has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving biotic functions using only the most thermodynamically stable amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids. In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as bio-mining, human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

A systematic review of synthetic and biologic materials for abdominal wall reinforcement in contaminated fields.

PubMed

Lee, Lawrence; Mata, Juan; Landry, Tara; Khwaja, Kosar A; Vassiliou, Melina C; Fried, Gerald M; Feldman, Liane S

2014-09-01

Guidelines recommend the use of bioprosthetics for abdominal wall reinforcement in contaminated fields, but the evidence supporting the use of biologic over synthetic non-absorbable prosthetics for this indication is poor. Therefore, the objective was to perform a systematic review of outcomes after synthetic non-absorbable and biologic prosthetics for ventral hernia repair or prophylaxis in contaminated fields. The systematic literature search identified all articles published up to 2013 that reported outcomes after abdominal wall reinforcement using synthetic non-absorbable or biologic prosthetics in contaminated fields. Studies were included if they included at least 10 cases (excluding inguinal and parastomal hernias). Quality assessment was performed using the MINORS instrument. The main outcomes measures were the incidence of wound infection and hernia at follow-up. Weighted pooled proportions were calculated using a random effects model. A total of 32 studies met the inclusion criteria and were included for synthesis. Mean sample size was 41.4 (range 10-190), and duration of follow-up was >1 year in 72 % of studies. Overall quality was low (mean 6.2, range 1-12). Pooled wound infection rates were 31.6 % (95 % CI 14.5-48.7) with biologic and 6.4 % (95 % CI 3.4-9.4) with synthetic non-absorbable prosthetics in clean-contaminated cases, with similar hernia rates. In contaminated and/or dirty fields, wound infection rates were similar, but pooled hernia rates were 27.2 % (95 % CI 9.5-44.9) with biologic and 3.2 % (95 % CI 0.0-11.0) with synthetic non-absorbable. Other outcomes were comparable. The available evidence is limited, but does not support the superiority of biologic over synthetic non-absorbable prosthetics in contaminated fields.

The ethical landscape: identifying the right way to think about the ethical and societal aspects of synthetic biology research and products

PubMed Central

Yearley, Steven

2009-01-01

Synthetic biology promises to be highly innovative in its contribution to scientific understanding. But it offers other sorts of innovation too: in the variety of applications that could result and in the wide range of practitioners who could become involved. But directly corresponding to each of these is a kind of regulatory concern. If the entry barriers are low for a form of scientific practice with dramatic implications then the need for regulatory control over access is great since no one wants unlicensed operators releasing experimental organisms. If there are likely to be extensive opportunities for application within the human body and in the open environment (for energy production or novel forms of bioremediation) then the release and safety-testing implications are potentially enormous. Proponents of synthetic biology have been quick to realise that these challenges call for reviews of the societal and ethical aspects of synthetic biology. This paper shows that the template commonly adopted for such reviews draws on bioethics. It goes on to show that this template is far from ideal, both because of limitations in the way that bioethics has been institutionalized and because of key differences between the regulatory demands on synthetic biology and on bioethics. The paper concludes that broader models of societal and ethical review of synthetic biology are urgently required. PMID:19447816

Synthetic biology of cyanobacteria: unique challenges and opportunities

PubMed Central

Berla, Bertram M.; Saha, Rajib; Immethun, Cheryl M.; Maranas, Costas D.; Moon, Tae Seok; Pakrasi, Himadri B.

2013-01-01

Photosynthetic organisms, and especially cyanobacteria, hold great promise as sources of renewably-produced fuels, bulk and specialty chemicals, and nutritional products. Synthetic biology tools can help unlock cyanobacteria's potential for these functions, but unfortunately tool development for these organisms has lagged behind that for S. cerevisiae and E. coli. While these organisms may in many cases be more difficult to work with as “chassis” strains for synthetic biology than certain heterotrophs, the unique advantages of autotrophs in biotechnology applications as well as the scientific importance of improved understanding of photosynthesis warrant the development of these systems into something akin to a “green E. coli.” In this review, we highlight unique challenges and opportunities for development of synthetic biology approaches in cyanobacteria. We review classical and recently developed methods for constructing targeted mutants in various cyanobacterial strains, and offer perspective on what genetic tools might most greatly expand the ability to engineer new functions in such strains. Similarly, we review what genetic parts are most needed for the development of cyanobacterial synthetic biology. Finally, we highlight recent methods to construct genome-scale models of cyanobacterial metabolism and to use those models to measure properties of autotrophic metabolism. Throughout this paper, we discuss some of the unique challenges of a diurnal, autotrophic lifestyle along with how the development of synthetic biology and biotechnology in cyanobacteria must fit within those constraints. PMID:24009604

Cell-free synthetic biology for environmental sensing and remediation.

PubMed

Karig, David K

2017-06-01

The fields of biosensing and bioremediation leverage the phenomenal array of sensing and metabolic capabilities offered by natural microbes. Synthetic biology provides tools for transforming these fields through complex integration of natural and novel biological components to achieve sophisticated sensing, regulation, and metabolic function. However, the majority of synthetic biology efforts are conducted in living cells, and concerns over releasing genetically modified organisms constitute a key barrier to environmental applications. Cell-free protein expression systems offer a path towards leveraging synthetic biology, while preventing the spread of engineered organisms in nature. Recent efforts in the areas of cell-free approaches for sensing, regulation, and metabolic pathway implementation, as well as for preserving and deploying cell-free expression components, embody key steps towards realizing the potential of cell-free systems for environmental sensing and remediation. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

How to turn a genetic circuit into a synthetic tunable oscillator, or a bistable switch.

PubMed

Marucci, Lucia; Barton, David A W; Cantone, Irene; Ricci, Maria Aurelia; Cosma, Maria Pia; Santini, Stefania; di Bernardo, Diego; di Bernardo, Mario

2009-12-07

Systems and Synthetic Biology use computational models of biological pathways in order to study in silico the behaviour of biological pathways. Mathematical models allow to verify biological hypotheses and to predict new possible dynamical behaviours. Here we use the tools of non-linear analysis to understand how to change the dynamics of the genes composing a novel synthetic network recently constructed in the yeast Saccharomyces cerevisiae for In-vivo Reverse-engineering and Modelling Assessment (IRMA). Guided by previous theoretical results that make the dynamics of a biological network depend on its topological properties, through the use of simulation and continuation techniques, we found that the network can be easily turned into a robust and tunable synthetic oscillator or a bistable switch. Our results provide guidelines to properly re-engineering in vivo the network in order to tune its dynamics.

Engineering plant metabolism into microbes: from systems biology to synthetic biology.

PubMed

Xu, Peng; Bhan, Namita; Koffas, Mattheos A G

2013-04-01

Plant metabolism represents an enormous repository of compounds that are of pharmaceutical and biotechnological importance. Engineering plant metabolism into microbes will provide sustainable solutions to produce pharmaceutical and fuel molecules that could one day replace substantial portions of the current fossil-fuel based economy. Metabolic engineering entails targeted manipulation of biosynthetic pathways to maximize yields of desired products. Recent advances in Systems Biology and the emergence of Synthetic Biology have accelerated our ability to design, construct and optimize cell factories for metabolic engineering applications. Progress in predicting and modeling genome-scale metabolic networks, versatile gene assembly platforms and delicate synthetic pathway optimization strategies has provided us exciting opportunities to exploit the full potential of cell metabolism. In this review, we will discuss how systems and synthetic biology tools can be integrated to create tailor-made cell factories for efficient production of natural products and fuel molecules in microorganisms. Copyright © 2012 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

Selection platforms for directed evolution in synthetic biology

PubMed Central

Tizei, Pedro A.G.; Csibra, Eszter; Torres, Leticia; Pinheiro, Vitor B.

2016-01-01

Life on Earth is incredibly diverse. Yet, underneath that diversity, there are a number of constants and highly conserved processes: all life is based on DNA and RNA; the genetic code is universal; biology is limited to a small subset of potential chemistries. A vast amount of knowledge has been accrued through describing and characterizing enzymes, biological processes and organisms. Nevertheless, much remains to be understood about the natural world. One of the goals in Synthetic Biology is to recapitulate biological complexity from simple systems made from biological molecules–gaining a deeper understanding of life in the process. Directed evolution is a powerful tool in Synthetic Biology, able to bypass gaps in knowledge and capable of engineering even the most highly conserved biological processes. It encompasses a range of methodologies to create variation in a population and to select individual variants with the desired function–be it a ligand, enzyme, pathway or even whole organisms. Here, we present some of the basic frameworks that underpin all evolution platforms and review some of the recent contributions from directed evolution to synthetic biology, in particular methods that have been used to engineer the Central Dogma and the genetic code. PMID:27528765

Selection platforms for directed evolution in synthetic biology.

PubMed

Tizei, Pedro A G; Csibra, Eszter; Torres, Leticia; Pinheiro, Vitor B

2016-08-15

Life on Earth is incredibly diverse. Yet, underneath that diversity, there are a number of constants and highly conserved processes: all life is based on DNA and RNA; the genetic code is universal; biology is limited to a small subset of potential chemistries. A vast amount of knowledge has been accrued through describing and characterizing enzymes, biological processes and organisms. Nevertheless, much remains to be understood about the natural world. One of the goals in Synthetic Biology is to recapitulate biological complexity from simple systems made from biological molecules-gaining a deeper understanding of life in the process. Directed evolution is a powerful tool in Synthetic Biology, able to bypass gaps in knowledge and capable of engineering even the most highly conserved biological processes. It encompasses a range of methodologies to create variation in a population and to select individual variants with the desired function-be it a ligand, enzyme, pathway or even whole organisms. Here, we present some of the basic frameworks that underpin all evolution platforms and review some of the recent contributions from directed evolution to synthetic biology, in particular methods that have been used to engineer the Central Dogma and the genetic code. © 2016 The Author(s).

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).

Sender–receiver systems and applying information theory for quantitative synthetic biology

PubMed Central

Barcena Menendez, Diego; Senthivel, Vivek Raj; Isalan, Mark

2015-01-01

Sender–receiver (S–R) systems abound in biology, with communication systems sending information in various forms. Information theory provides a quantitative basis for analysing these processes and is being applied to study natural genetic, enzymatic and neural networks. Recent advances in synthetic biology are providing us with a wealth of artificial S–R systems, giving us quantitative control over networks with a finite number of well-characterised components. Combining the two approaches can help to predict how to maximise signalling robustness, and will allow us to make increasingly complex biological computers. Ultimately, pushing the boundaries of synthetic biology will require moving beyond engineering the flow of information and towards building more sophisticated circuits that interpret biological meaning. PMID:25282688

Chromatin regulation at the frontier of synthetic biology.

PubMed

Keung, Albert J; Joung, J Keith; Khalil, Ahmad S; Collins, James J

2015-03-01

As synthetic biology approaches are extended to diverse applications throughout medicine, biotechnology and basic biological research, there is an increasing need to engineer yeast, plant and mammalian cells. Eukaryotic genomes are regulated by the diverse biochemical and biophysical states of chromatin, which brings distinct challenges, as well as opportunities, over applications in bacteria. Recent synthetic approaches, including 'epigenome editing', have allowed the direct and functional dissection of many aspects of physiological chromatin regulation. These studies lay the foundation for biomedical and biotechnological engineering applications that could take advantage of the unique combinatorial and spatiotemporal layers of chromatin regulation to create synthetic systems of unprecedented sophistication.

From a word to a world: the current situation in the interdisciplinary field of synthetic biology

PubMed Central

Hu, Xiaojun

2015-01-01

Using a carefully designed search query, we describe the field of synthetic biology in terms of leading countries, organizations and funding sources. Besides articles we also paid some attention to patents. The USA is the leading country in this field, followed by China. There is a clear exponential growth in the field of synthetic biology over the latest 14 years. Keywords were analyzed using the notion of year-based h-indices, core gap and relative core gap. We conclude that the term “synthetic biology” hides a large world ready to be explored by interdisciplinary research. PMID:25650074

Chromatin regulation at the frontier of synthetic biology

PubMed Central

Keung, Albert J.; Joung, J. Keith; Khalil, Ahmad S.; Collins, James J.

2016-01-01

As synthetic biology approaches are extended to diverse applications throughout medicine, biotechnology and basic biological research, there is an increasing need to engineer yeast, plant and mammalian cells. Eukaryotic genomes are regulated by the diverse biochemical and biophysical states of chromatin, which brings distinct challenges, as well as opportunities, over applications in bacteria. Recent synthetic approaches, including `epigenome editing', have allowed the direct and functional dissection of many aspects of physiological chromatin regulation. These studies lay the foundation for biomedical and biotechnological engineering applications that could take advantage of the unique combinatorial and spatiotemporal layers of chromatin regulation to create synthetic systems of unprecedented sophistication. PMID:25668787

Economic Burden and Treatment Patterns of Cycling between Conventional Synthetic Disease-modifying Antirheumatic Drugs Among Biologic-treated Patients with Rheumatoid Arthritis.

PubMed

Betts, Keith A; Griffith, Jenny; Ganguli, Arijit; Li, Nanxin; Douglas, Kevin; Wu, Eric Q

2016-05-01

To assess the economic outcomes and treatment patterns among patients with rheumatoid arthritis (RA) who used 1, 2, or 3 or more conventional synthetic disease-modifying antirheumatic drugs (DMARDs) before receiving a biologic therapy. Adult patients with ≥2 RA diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 714.xx) on different dates, ≥1 claim for a conventional synthetic DMARD, and ≥1 claim for a biologic DMARD were identified from a large commercial claims database. The initiation date of the first biologic DMARD was defined as the index date. Based on the number of distinct conventional synthetic DMARDs initiated between the first RA diagnosis and the index date, patients were classified into 3 cohorts: those who used 1, 2, or 3 or more conventional synthetic DMARDs. Baseline characteristics were measured 6 months preindex date and compared between the 3 cohorts. All-cause health care costs (in 2014 US$) were compared during the follow-up period (12 months postbiologic initiation) using multivariable gamma models adjusting for baseline characteristics. Time to discontinuation of the index biologic DMARD and time to switching to a new DMARD were compared using multivariable Cox proportional hazards models. The 1, 2, and 3 or more conventional synthetic DMARD cohorts included 6215; 3227; and 976 patients, respectively. At baseline, patients in the 3 or more conventional synthetic DMARD cohort had the least severe RA, as indicated by the lowest claims-based index for RA severity score (1 vs 2 vs 3 or more = 6.1 vs 5.9 vs 5.8). During the study period, there was a significant association between number of conventional synthetic DMARDs and higher all-cause total health care costs (adjusted mean difference, 1 vs 2: $772; P < 0.001; 2 vs 3 or more: $2390; P < 0.001). The all-cause medical and pharmacy costs were also significantly higher with the increasing number of conventional synthetic DMARDs. Patients who cycled more conventional synthetic DMARDs were also more likely to switch treatment after biologic initiation (1 vs 2: adjusted hazard ratio = 0.89; P = 0.005; 2 vs 3 or more: adjusted hazard ratio = 0.89; P = 0.087). There were no differences in index biologic discontinuation between the 3 cohorts. Patients with RA who cycled more conventional synthetic DMARDs had increased economic burden in the 12 months following biologic initiation and were more likely to switch therapy. These results highlight the importance of timely switching to biologic DMARDs for the treatment of RA. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Synthetic Biology and the Moral Significance of Artificial Life: A Reply to Douglas, Powell and Savulescu.

PubMed

Christiansen, Andreas

2016-06-01

I discuss the moral significance of artificial life within synthetic biology via a discussion of Douglas, Powell and Savulescu's paper 'Is the creation of artificial life morally significant'. I argue that the definitions of 'artificial life' and of 'moral significance' are too narrow. Douglas, Powell and Savulescu's definition of artificial life does not capture all core projects of synthetic biology or the ethical concerns that have been voiced, and their definition of moral significance fails to take into account the possibility that creating artificial life is conditionally acceptable. Finally, I show how several important objections to synthetic biology are plausibly understood as arguing that creating artificial life in a wide sense is only conditionally acceptable. © 2016 John Wiley & Sons Ltd.

[Advance in flavonoids biosynthetic pathway and synthetic biology].

PubMed

Zou, Li-Qiu; Wang, Cai-Xia; Kuang, Xue-Jun; Li, Ying; Sun, Chao

2016-11-01

Flavonoids are the valuable components in medicinal plants, which possess a variety of pharmacological activities, including anti-tumor, antioxidant and anti-inflammatory activities. There is an unambiguous understanding about flavonoids biosynthetic pathway, that is,2S-flavanones including naringenin and pinocembrin are the skeleton of other flavonoids and they can transform to other flavonoids through branched metabolic pathway. Elucidation of the flavonoids biosynthetic pathway lays a solid foundation for their synthetic biology. A few flavonoids have been produced in Escherichia coli or yeast with synthetic biological technologies, such as naringenin, pinocembrin and fisetin. Synthetic biology will provide a new way to get valuable flavonoids and promote the research and development of flavonoid drugs and health products, making flavonoids play more important roles in human diet and health. Copyright© by the Chinese Pharmaceutical Association.

Modularization of genetic elements promotes synthetic metabolic engineering.

PubMed

Qi, Hao; Li, Bing-Zhi; Zhang, Wen-Qian; Liu, Duo; Yuan, Ying-Jin

2015-11-15

In the context of emerging synthetic biology, metabolic engineering is moving to the next stage powered by new technologies. Systematical modularization of genetic elements makes it more convenient to engineer biological systems for chemical production or other desired purposes. In the past few years, progresses were made in engineering metabolic pathway using synthetic biology tools. Here, we spotlighted the topic of implementation of modularized genetic elements in metabolic engineering. First, we overviewed the principle developed for modularizing genetic elements and then discussed how the genetic modules advanced metabolic engineering studies. Next, we picked up some milestones of engineered metabolic pathway achieved in the past few years. Last, we discussed the rapid raised synthetic biology field of "building a genome" and the potential in metabolic engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

Synthetic methylotrophy: engineering the production of biofuels and chemicals based on the biology of aerobic methanol utilization.

PubMed

Whitaker, William B; Sandoval, Nicholas R; Bennett, Robert K; Fast, Alan G; Papoutsakis, Eleftherios T

2015-06-01

Synthetic methylotrophy is the development of non-native methylotrophs that can utilize methane and methanol as sole carbon and energy sources or as co-substrates with carbohydrates to produce metabolites as biofuels and chemicals. The availability of methane (from natural gas) and its oxidation product, methanol, has been increasing, while prices have been decreasing, thus rendering them as attractive fermentation substrates. As they are more reduced than most carbohydrates, methane and methanol, as co-substrates, can enhance the yields of biologically produced metabolites. Here we discuss synthetic biology and metabolic engineering strategies based on the native biology of aerobic methylotrophs for developing synthetic strains grown on methanol, with Escherichia coli as the prototype. Copyright © 2015. Published by Elsevier Ltd.

Synthetic biology and the ethics of knowledge

PubMed Central

Douglas, Thomas; Savulescu, Julian

2011-01-01

Synthetic biologists aim to generate biological organisms according to rational design principles. Their work may have many beneficial applications, but it also raises potentially serious ethical concerns. In this article, we consider what attention the discipline demands from bioethicists. We argue that the most important issue for ethicists to examine is the risk that knowledge from synthetic biology will be misused, for example, in biological terrorism or warfare. To adequately address this concern, bioethics will need to broaden its scope, contemplating not just the means by which scientific knowledge is produced, but also what kinds of knowledge should be sought and disseminated. PMID:20935316

Emerging biomedical applications of synthetic biology.

PubMed

Weber, Wilfried; Fussenegger, Martin

2011-11-29

Synthetic biology aims to create functional devices, systems and organisms with novel and useful functions on the basis of catalogued and standardized biological building blocks. Although they were initially constructed to elucidate the dynamics of simple processes, designed devices now contribute to the understanding of disease mechanisms, provide novel diagnostic tools, enable economic production of therapeutics and allow the design of novel strategies for the treatment of cancer, immune diseases and metabolic disorders, such as diabetes and gout, as well as a range of infectious diseases. In this Review, we cover the impact and potential of synthetic biology for biomedical applications.

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.

Rational Diversification of a Promoter Providing Fine-Tuned Expression and Orthogonal Regulation for Synthetic Biology

PubMed Central

Blount, Benjamin A.; Weenink, Tim; Vasylechko, Serge; Ellis, Tom

2012-01-01

Yeast is an ideal organism for the development and application of synthetic biology, yet there remain relatively few well-characterised biological parts suitable for precise engineering of this chassis. In order to address this current need, we present here a strategy that takes a single biological part, a promoter, and re-engineers it to produce a fine-graded output range promoter library and new regulated promoters desirable for orthogonal synthetic biology applications. A highly constitutive Saccharomyces cerevisiae promoter, PFY1p, was identified by bioinformatic approaches, characterised in vivo and diversified at its core sequence to create a 36-member promoter library. TetR regulation was introduced into PFY1p to create a synthetic inducible promoter (iPFY1p) that functions in an inverter device. Orthogonal and scalable regulation of synthetic promoters was then demonstrated for the first time using customisable Transcription Activator-Like Effectors (TALEs) modified and designed to act as orthogonal repressors for specific PFY1-based promoters. The ability to diversify a promoter at its core sequences and then independently target Transcription Activator-Like Orthogonal Repressors (TALORs) to virtually any of these sequences shows great promise toward the design and construction of future synthetic gene networks that encode complex “multi-wire” logic functions. PMID:22442681

Rational diversification of a promoter providing fine-tuned expression and orthogonal regulation for synthetic biology.

PubMed

Blount, Benjamin A; Weenink, Tim; Vasylechko, Serge; Ellis, Tom

2012-01-01

Yeast is an ideal organism for the development and application of synthetic biology, yet there remain relatively few well-characterised biological parts suitable for precise engineering of this chassis. In order to address this current need, we present here a strategy that takes a single biological part, a promoter, and re-engineers it to produce a fine-graded output range promoter library and new regulated promoters desirable for orthogonal synthetic biology applications. A highly constitutive Saccharomyces cerevisiae promoter, PFY1p, was identified by bioinformatic approaches, characterised in vivo and diversified at its core sequence to create a 36-member promoter library. TetR regulation was introduced into PFY1p to create a synthetic inducible promoter (iPFY1p) that functions in an inverter device. Orthogonal and scalable regulation of synthetic promoters was then demonstrated for the first time using customisable Transcription Activator-Like Effectors (TALEs) modified and designed to act as orthogonal repressors for specific PFY1-based promoters. The ability to diversify a promoter at its core sequences and then independently target Transcription Activator-Like Orthogonal Repressors (TALORs) to virtually any of these sequences shows great promise toward the design and construction of future synthetic gene networks that encode complex "multi-wire" logic functions.

[Synthetic biology toward microbial secondary metabolites and pharmaceuticals].

PubMed

Wu, Lin-Zhuan; Hong, Bin

2013-02-01

Microbial secondary metabolites are one of the major sources of anti-bacterial, anti-fungal, antitumor, anti-virus and immunosuppressive agents for clinical use. Present challenges in microbial pharmaceutical development are the discovery of novel secondary metabolites with significant biological activities, improving the fermentation titers of industrial microbial strains, and production of natural product drugs by re-establishing their biosynthetic pathways in suitable microbial hosts. Synthetic biology, which is developed from systematic biology and metabolic engineering, provides a significant driving force for microbial pharmaceutical development. The review describes the major applications of synthetic biology in novel microbial secondary metabolite discovery, improved production of known secondary metabolites and the production of some natural drugs in genetically modified or reconstructed model microorganisms.

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.

Synthetic biology meets tissue engineering

PubMed Central

Davies, Jamie A.; Cachat, Elise

2016-01-01

Classical tissue engineering is aimed mainly at producing anatomically and physiologically realistic replacements for normal human tissues. It is done either by encouraging cellular colonization of manufactured matrices or cellular recolonization of decellularized natural extracellular matrices from donor organs, or by allowing cells to self-organize into organs as they do during fetal life. For repair of normal bodies, this will be adequate but there are reasons for making unusual, non-evolved tissues (repair of unusual bodies, interface to electromechanical prostheses, incorporating living cells into life-support machines). Synthetic biology is aimed mainly at engineering cells so that they can perform custom functions: applying synthetic biological approaches to tissue engineering may be one way of engineering custom structures. In this article, we outline the ‘embryological cycle’ of patterning, differentiation and morphogenesis and review progress that has been made in constructing synthetic biological systems to reproduce these processes in new ways. The state-of-the-art remains a long way from making truly synthetic tissues, but there are now at least foundations for future work. PMID:27284030

Purified high molecular weight synthetic Aβ(1-42) and biological Aβ oligomers are equipotent in rapidly inducing MTT formazan exocytosis.

PubMed

Weidner, Adam M; Housley, Molly; Murphy, M Paul; Levine, Harry

2011-06-15

Synthetic soluble Aβ oligomers are often used as a surrogate for biologic material in a number of model systems. We compared the activity of Aβ oligomers (synthetic and cell culture media derived) on the human SH-SY5Y neuroblastoma and C2C12 mouse myoblast cell lines in a novel, modified MTT assay. Separating oligomers from monomeric peptide by size exclusion chromatography produced effects at peptide concentrations approaching physiologic levels (10-100 nM). Purified oligomers, but not monomers or fibrils, elicited an increase of a detergent-insoluble form of MTT formazan within 2h as opposed to a control toxin (H(2)O(2)). This effect was comparable for biological and synthetic peptide in both cell types. Monomeric Aβ attenuated the effect of soluble oligomers. This study suggests that the activities of biological and synthetic oligomers are indistinguishable during early stages of Aβ oligomer-cell interaction. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Synthetic biology devices for in vitro and in vivo diagnostics.

PubMed

Slomovic, Shimyn; Pardee, Keith; Collins, James J

2015-11-24

There is a growing need to enhance our capabilities in medical and environmental diagnostics. Synthetic biologists have begun to focus their biomolecular engineering approaches toward this goal, offering promising results that could lead to the development of new classes of inexpensive, rapidly deployable diagnostics. Many conventional diagnostics rely on antibody-based platforms that, although exquisitely sensitive, are slow and costly to generate and cannot readily confront rapidly emerging pathogens or be applied to orphan diseases. Synthetic biology, with its rational and short design-to-production cycles, has the potential to overcome many of these limitations. Synthetic biology devices, such as engineered gene circuits, bring new capabilities to molecular diagnostics, expanding the molecular detection palette, creating dynamic sensors, and untethering reactions from laboratory equipment. The field is also beginning to move toward in vivo diagnostics, which could provide near real-time surveillance of multiple pathological conditions. Here, we describe current efforts in synthetic biology, focusing on the translation of promising technologies into pragmatic diagnostic tools and platforms.

Synthetic biology devices for in vitro and in vivo diagnostics

PubMed Central

Slomovic, Shimyn; Pardee, Keith; Collins, James J.

2015-01-01

There is a growing need to enhance our capabilities in medical and environmental diagnostics. Synthetic biologists have begun to focus their biomolecular engineering approaches toward this goal, offering promising results that could lead to the development of new classes of inexpensive, rapidly deployable diagnostics. Many conventional diagnostics rely on antibody-based platforms that, although exquisitely sensitive, are slow and costly to generate and cannot readily confront rapidly emerging pathogens or be applied to orphan diseases. Synthetic biology, with its rational and short design-to-production cycles, has the potential to overcome many of these limitations. Synthetic biology devices, such as engineered gene circuits, bring new capabilities to molecular diagnostics, expanding the molecular detection palette, creating dynamic sensors, and untethering reactions from laboratory equipment. The field is also beginning to move toward in vivo diagnostics, which could provide near real-time surveillance of multiple pathological conditions. Here, we describe current efforts in synthetic biology, focusing on the translation of promising technologies into pragmatic diagnostic tools and platforms. PMID:26598662

Automatic Design of Synthetic Gene Circuits through Mixed Integer Non-linear Programming

PubMed Central

Huynh, Linh; Kececioglu, John; Köppe, Matthias; Tagkopoulos, Ilias

2012-01-01

Automatic design of synthetic gene circuits poses a significant challenge to synthetic biology, primarily due to the complexity of biological systems, and the lack of rigorous optimization methods that can cope with the combinatorial explosion as the number of biological parts increases. Current optimization methods for synthetic gene design rely on heuristic algorithms that are usually not deterministic, deliver sub-optimal solutions, and provide no guaranties on convergence or error bounds. Here, we introduce an optimization framework for the problem of part selection in synthetic gene circuits that is based on mixed integer non-linear programming (MINLP), which is a deterministic method that finds the globally optimal solution and guarantees convergence in finite time. Given a synthetic gene circuit, a library of characterized parts, and user-defined constraints, our method can find the optimal selection of parts that satisfy the constraints and best approximates the objective function given by the user. We evaluated the proposed method in the design of three synthetic circuits (a toggle switch, a transcriptional cascade, and a band detector), with both experimentally constructed and synthetic promoter libraries. Scalability and robustness analysis shows that the proposed framework scales well with the library size and the solution space. The work described here is a step towards a unifying, realistic framework for the automated design of biological circuits. PMID:22536398

Rewiring protein synthesis: From natural to synthetic amino acids.

PubMed

Fan, Yongqiang; Evans, Christopher R; Ling, Jiqiang

2017-11-01

The protein synthesis machinery uses 22 natural amino acids as building blocks that faithfully decode the genetic information. Such fidelity is controlled at multiple steps and can be compromised in nature and in the laboratory to rewire protein synthesis with natural and synthetic amino acids. This review summarizes the major quality control mechanisms during protein synthesis, including aminoacyl-tRNA synthetases, elongation factors, and the ribosome. We will discuss evolution and engineering of such components that allow incorporation of natural and synthetic amino acids at positions that deviate from the standard genetic code. The protein synthesis machinery is highly selective, yet not fixed, for the correct amino acids that match the mRNA codons. Ambiguous translation of a codon with multiple amino acids or complete reassignment of a codon with a synthetic amino acid diversifies the proteome. Expanding the genetic code with synthetic amino acids through rewiring protein synthesis has broad applications in synthetic biology and chemical biology. Biochemical, structural, and genetic studies of the translational quality control mechanisms are not only crucial to understand the physiological role of translational fidelity and evolution of the genetic code, but also enable us to better design biological parts to expand the proteomes of synthetic organisms. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier B.V. All rights reserved.

Experiential Engineering through iGEM--An Undergraduate Summer Competition in Synthetic Biology

ERIC Educational Resources Information Center

Mitchell, Rudolph; Dori, Yehudit Judy; Kuldell, Natalie H.

2011-01-01

Unlike students in other engineering disciplines, undergraduates in biological engineering typically have limited opportunity to develop design competencies, and even fewer chances to implement their designed projects. The international Genetically Engineered Machines (iGEM) competition is a student Synthetic Biology competition that, in 2009,…

77 FR 59933 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-01

... Special Emphasis Panel; Synthetic and Biological Chemistry A. Date: October 22, 2012. Time: 1:00 a.m. to 2... 20892, (301) 435-1726, [email protected] . Name of Committee: Biological Chemistry and Macromolecular Biophysics Integrated Review Group; Synthetic and Biological Chemistry A Study Section. Date...

Synthetic Biology: Putting Synthesis into Biology

PubMed Central

Liang, Jing; Luo, Yunzi; Zhao, Huimin

2010-01-01

The ability to manipulate living organisms is at the heart of a range of emerging technologies that serve to address important and current problems in environment, energy, and health. However, with all its complexity and interconnectivity, biology has for many years been recalcitrant to engineering manipulations. The recent advances in synthesis, analysis, and modeling methods have finally provided the tools necessary to manipulate living systems in meaningful ways, and have led to the coining of a field named synthetic biology. The scope of synthetic biology is as complicated as life itself – encompassing many branches of science, and across many scales of application. New DNA synthesis and assembly techniques have made routine the customization of very large DNA molecules. This in turn has allowed the incorporation of multiple genes and pathways. By coupling these with techniques that allow for the modeling and design of protein functions, scientists have now gained the tools to create completely novel biological machineries. Even the ultimate biological machinery – a self-replicating organism – is being pursued at this moment. It is the purpose of this review to dissect and organize these various components of synthetic biology into a coherent picture. PMID:21064036

Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo.

PubMed

Sharma, Sunil V; Tong, Xiaoxue; Pubill-Ulldemolins, Cristina; Cartmell, Christopher; Bogosyan, Emma J A; Rackham, Emma J; Marelli, Enrico; Hamed, Refaat B; Goss, Rebecca J M

2017-08-09

Marrying synthetic biology with synthetic chemistry provides a powerful approach toward natural product diversification, combining the best of both worlds: expediency and synthetic capability of biogenic pathways and chemical diversity enabled by organic synthesis. Biosynthetic pathway engineering can be employed to insert a chemically orthogonal tag into a complex natural scaffold affording the possibility of site-selective modification without employing protecting group strategies. Here we show that, by installing a sufficiently reactive handle (e.g., a C-Br bond) and developing compatible mild aqueous chemistries, synchronous biosynthesis of the tagged metabolite and its subsequent chemical modification in living culture can be achieved. This approach can potentially enable many new applications: for example, assay of directed evolution of enzymes catalyzing halo-metabolite biosynthesis in living cells or generating and following the fate of tagged metabolites and biomolecules in living systems. We report synthetic biological access to new-to-nature bromo-metabolites and the concomitant biorthogonal cross-coupling of halo-metabolites in living cultures.Coupling synthetic biology and chemical reactions in cells is a challenging task. The authors engineer bacteria capable of generating bromo-metabolites, develop a mild Suzuki-Miyaura cross-coupling reaction compatible with cell growth and carry out the cross-coupling chemistry in live cell cultures.

Where Synthetic Biology Meets ET

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2016-01-01

Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. And what about the limits for life? Can we create organisms that expand the envelope for life? In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

Yeast synthetic biology for high-value metabolites.

PubMed

Dai, Zhubo; Liu, Yi; Guo, Juan; Huang, Luqi; Zhang, Xueli

2015-02-01

Traditionally, high-value metabolites have been produced through direct extraction from natural biological sources which are inefficient, given the low abundance of these compounds. On the other hand, these high-value metabolites are usually difficult to be synthesized chemically, due to their complex structures. In the last few years, the discovery of genes involved in the synthetic pathways of these metabolites, combined with advances in synthetic biology tools, has allowed the construction of increasing numbers of yeast cell factories for production of these metabolites from renewable biomass. This review summarizes recent advances in synthetic biology in terms of the use of yeasts as microbial hosts for the identification of the pathways involved in the synthesis, as well as for the production of high-value metabolites. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Behavioral Economics and the Public Acceptance of Synthetic Biology.

PubMed

Oliver, Adam

2018-01-01

Different applications of synthetic biology are alike in that their possible negative consequences are highly uncertain, potentially catastrophic, and perhaps irreversible; therefore, they are also alike in that public attitudes about them are fertile ground for behavioral economic phenomena. Findings from behavioral economics suggest that people may not respond to such applications according to the normal rules of economic evaluation, by which the value of an outcome is multiplied by the mathematical probability that the outcome will occur. Possibly, then, synthetic biology applications challenge the normative postulates of the standard approach, too. I want to first consider how some of the phenomena described by behavioral economists-and behavioral scientists more broadly-might affect people's perceptions of the uncertainties associated with synthetic biology. My analysis will be far from complete, however, because behavioral economics is essentially the study of human behavior, and thus its reach is potentially vast and its development longstanding and ongoing. Nonetheless, I hope to give an indicative perspective on how some aspects of behavioral economics might affect the assessment and perceived acceptability of synthetic biology. I will then consider the issue of agency. Should policy-makers respect people's reactions to synthetic biology when those reactions are known to be driven by behavioral economic phenomena rather than following the normative postulates of rational choice theory? Or should policy-makers dismiss these reactions as inherently biased? I will argue that the normative force of these human reactions (probably) depends on phenomenon and context. © 2018 The Hastings Center.

Synthetic Biology: A Unifying View and Review Using Analog Circuits.

PubMed

Teo, Jonathan J Y; Woo, Sung Sik; Sarpeshkar, Rahul

2015-08-01

We review the field of synthetic biology from an analog circuits and analog computation perspective, focusing on circuits that have been built in living cells. This perspective is well suited to pictorially, symbolically, and quantitatively representing the nonlinear, dynamic, and stochastic (noisy) ordinary and partial differential equations that rigorously describe the molecular circuits of synthetic biology. This perspective enables us to construct a canonical analog circuit schematic that helps unify and review the operation of many fundamental circuits that have been built in synthetic biology at the DNA, RNA, protein, and small-molecule levels over nearly two decades. We review 17 circuits in the literature as particular examples of feedforward and feedback analog circuits that arise from special topological cases of the canonical analog circuit schematic. Digital circuit operation of these circuits represents a special case of saturated analog circuit behavior and is automatically incorporated as well. Many issues that have prevented synthetic biology from scaling are naturally represented in analog circuit schematics. Furthermore, the deep similarity between the Boltzmann thermodynamic equations that describe noisy electronic current flow in subthreshold transistors and noisy molecular flux in biochemical reactions has helped map analog circuit motifs in electronics to analog circuit motifs in cells and vice versa via a `cytomorphic' approach. Thus, a body of knowledge in analog electronic circuit design, analysis, simulation, and implementation may also be useful in the robust and efficient design of molecular circuits in synthetic biology, helping it to scale to more complex circuits in the future.

Synthetic Astrobiology

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2015-01-01

Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

Cell-free synthetic biology for in vitro prototype engineering.

PubMed

Moore, Simon J; MacDonald, James T; Freemont, Paul S

2017-06-15

Cell-free transcription-translation is an expanding field in synthetic biology as a rapid prototyping platform for blueprinting the design of synthetic biological devices. Exemplar efforts include translation of prototype designs into medical test kits for on-site identification of viruses (Zika and Ebola), while gene circuit cascades can be tested, debugged and re-designed within rapid turnover times. Coupled with mathematical modelling, this discipline lends itself towards the precision engineering of new synthetic life. The next stages of cell-free look set to unlock new microbial hosts that remain slow to engineer and unsuited to rapid iterative design cycles. It is hoped that the development of such systems will provide new tools to aid the transition from cell-free prototype designs to functioning synthetic genetic circuits and engineered natural product pathways in living cells. © 2017 The Author(s).

Cell-free synthetic biology for in vitro prototype engineering

PubMed Central

Moore, Simon J.; MacDonald, James T.

2017-01-01

Cell-free transcription–translation is an expanding field in synthetic biology as a rapid prototyping platform for blueprinting the design of synthetic biological devices. Exemplar efforts include translation of prototype designs into medical test kits for on-site identification of viruses (Zika and Ebola), while gene circuit cascades can be tested, debugged and re-designed within rapid turnover times. Coupled with mathematical modelling, this discipline lends itself towards the precision engineering of new synthetic life. The next stages of cell-free look set to unlock new microbial hosts that remain slow to engineer and unsuited to rapid iterative design cycles. It is hoped that the development of such systems will provide new tools to aid the transition from cell-free prototype designs to functioning synthetic genetic circuits and engineered natural product pathways in living cells. PMID:28620040

Synthetic biology in mammalian cells: Next generation research tools and therapeutics

PubMed Central

Lienert, Florian; Lohmueller, Jason J; Garg, Abhishek; Silver, Pamela A

2014-01-01

Recent progress in DNA manipulation and gene circuit engineering has greatly improved our ability to programme and probe mammalian cell behaviour. These advances have led to a new generation of synthetic biology research tools and potential therapeutic applications. Programmable DNA-binding domains and RNA regulators are leading to unprecedented control of gene expression and elucidation of gene function. Rebuilding complex biological circuits such as T cell receptor signalling in isolation from their natural context has deepened our understanding of network motifs and signalling pathways. Synthetic biology is also leading to innovative therapeutic interventions based on cell-based therapies, protein drugs, vaccines and gene therapies. PMID:24434884

Human Health and Environmental Risks Posed by Synthetic Biology R&D for Energy Applications: A Literature Analysis

DOE PAGES

Hewett, Joel P.; Wolfe, Amy K.; Bergmann, Rachael A.; ...

2016-10-07

What are the human health and environmental risks posed by synthetic biology research and development (R&D) for energy applications? In this study, we found it surprisingly difficult to answer this seemingly straightforward question in our review of the risk-related synthetic biology literature. To our knowledge, no entity to date has published a comprehensive review of this literature. Thus, this analysis aims to fill that void and, at a high level, answer the question that we pose. Risk-related synthetic biology literature addresses risk from different perspectives. Much of the literature that we reviewed treats the concept of risk in synthetic biologymore » R&D broadly, enumerating few specific risks. Nevertheless, after reviewing >200 documents, we identified 44 discrete risk issues; 18 of those related to human health and 26 to the environment. We clustered these risk issues into categories that reflect and summarize their content. We categorized human health risk issues as follows: allergies, antibiotic resistance, carcinogens, and pathogenicity or toxicity. Environmental risk issues were categorized as follows: change or depletion of the environment, competition with native species, horizontal gene transfer, and pathogenicity or toxicity. Our efforts to understand what the synthetic biology R&D-related risk issues are stemmed from a larger research project in which we used risk issues identified in the literature as a point of departure in interviews with biosafety professionals and scientists engaged in synthetic biology R&D. Finally, we wrote this article after multiple biosafety professionals told us that accessing our risk-related literature analysis would aid them in their work.« less

Human Health and Environmental Risks Posed by Synthetic Biology R&D for Energy Applications: A Literature Analysis

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

Hewett, Joel P.; Wolfe, Amy K.; Bergmann, Rachael A.

What are the human health and environmental risks posed by synthetic biology research and development (R&D) for energy applications? In this study, we found it surprisingly difficult to answer this seemingly straightforward question in our review of the risk-related synthetic biology literature. To our knowledge, no entity to date has published a comprehensive review of this literature. Thus, this analysis aims to fill that void and, at a high level, answer the question that we pose. Risk-related synthetic biology literature addresses risk from different perspectives. Much of the literature that we reviewed treats the concept of risk in synthetic biologymore » R&D broadly, enumerating few specific risks. Nevertheless, after reviewing >200 documents, we identified 44 discrete risk issues; 18 of those related to human health and 26 to the environment. We clustered these risk issues into categories that reflect and summarize their content. We categorized human health risk issues as follows: allergies, antibiotic resistance, carcinogens, and pathogenicity or toxicity. Environmental risk issues were categorized as follows: change or depletion of the environment, competition with native species, horizontal gene transfer, and pathogenicity or toxicity. Our efforts to understand what the synthetic biology R&D-related risk issues are stemmed from a larger research project in which we used risk issues identified in the literature as a point of departure in interviews with biosafety professionals and scientists engaged in synthetic biology R&D. Finally, we wrote this article after multiple biosafety professionals told us that accessing our risk-related literature analysis would aid them in their work.« less

RNA and RNP as Building Blocks for Nanotechnology and Synthetic Biology.

PubMed

Ohno, Hirohisa; Saito, Hirohide

2016-01-01

Recent technologies that aimed to elucidate cellular function have revealed essential roles for RNA molecules in living systems. Our knowledge concerning functional and structural information of naturally occurring RNA and RNA-protein (RNP) complexes is increasing rapidly. RNA and RNP interaction motifs are structural units that function as building blocks to constitute variety of complex structures. RNA-central synthetic biology and nanotechnology are constructive approaches that employ the accumulated information and build synthetic RNA (RNP)-based circuits and nanostructures. Here, we describe how to design and construct synthetic RNA (RNP)-based devices and structures at the nanometer-scale for biological and future therapeutic applications. RNA/RNP nanostructures can also be utilized as the molecular scaffold to control the localization or interactions of target molecule(s). Moreover, RNA motifs recognized by RNA-binding proteins can be applied to make protein-responsive translational "switches" that can turn gene expression "on" or "off" depending on the intracellular environment. This "synthetic RNA and RNP world" will expand tools for nanotechnology and synthetic biology. In addition, these reconstructive approaches would lead to a greater understanding of building principle in naturally occurring RNA/RNP molecules and systems. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthetic biology and biomimetic chemistry as converging technologies fostering a new generation of smart biosensors.

PubMed

Scognamiglio, Viviana; Antonacci, Amina; Lambreva, Maya D; Litescu, Simona C; Rea, Giuseppina

2015-12-15

Biosensors are powerful tunable systems able to switch between an ON/OFF status in response to an external stimulus. This extraordinary property could be engineered by adopting synthetic biology or biomimetic chemistry to obtain tailor-made biosensors having the desired requirements of robustness, sensitivity and detection range. Recent advances in both disciplines, in fact, allow to re-design the configuration of the sensing elements - either by modifying toggle switches and gene networks, or by producing synthetic entities mimicking key properties of natural molecules. The present review considered the role of synthetic biology in sustaining biosensor technology, reporting examples from the literature and reflecting on the features that make it a useful tool for designing and constructing engineered biological systems for sensing application. Besides, a section dedicated to bioinspired synthetic molecules as powerful tools to enhance biosensor potential is reported, and treated as an extension of the concept of biomimetic chemistry, where organic synthesis is used to generate artificial molecules that mimic natural molecules. Thus, the design of synthetic molecules, such as aptamers, biomimetics, molecular imprinting polymers, peptide nucleic acids, and ribozymes were encompassed as "products" of biomimetic chemistry. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthetic biology regulation and governance: Lessons from TAPIC for the United States, European Union, and Singapore.

PubMed

Trump, Benjamin D

2017-11-01

Synthetic biology is an emerging technology with potential benefits to various fields, yet also contains potential risks to human and environmental health. The field remains in an emerging state with limited quantitative guidance and a small but growing population of international researchers that conduct work within this field. Given the uncertain nature of this technology, an adaptive and anticipatory governance framework may be necessary to balance the potential benefits that may accrue from the technology's continued research alongside a desire to reduce or eliminate potential risks that may arise. However, such developments must account for the unique political and institutional factors that form a government's risk culture - something that can facilitate or impede the development of adaptive synthetic biology governance moving forward. The TAPIC framework helps illustrate those factors that are essential to develop good governance for emerging technologies like synthetic biology. Specifically, an application of TAPIC to synthetic biology governance indicates that the factors of accountability, participation, and integrity must be bolstered to improve technology governance in governments like with the United States, European Union, and Singapore. Copyright © 2017. Published by Elsevier B.V.

Toward the First Data Acquisition Standard in Synthetic Biology.

PubMed

Sainz de Murieta, Iñaki; Bultelle, Matthieu; Kitney, Richard I

2016-08-19

This paper describes the development of a new data acquisition standard for synthetic biology. This comprises the creation of a methodology that is designed to capture all the data, metadata, and protocol information associated with biopart characterization experiments. The new standard, called DICOM-SB, is based on the highly successful Digital Imaging and Communications in Medicine (DICOM) standard in medicine. A data model is described which has been specifically developed for synthetic biology. The model is a modular, extensible data model for the experimental process, which can optimize data storage for large amounts of data. DICOM-SB also includes services orientated toward the automatic exchange of data and information between modalities and repositories. DICOM-SB has been developed in the context of systematic design in synthetic biology, which is based on the engineering principles of modularity, standardization, and characterization. The systematic design approach utilizes the design, build, test, and learn design cycle paradigm. DICOM-SB has been designed to be compatible with and complementary to other standards in synthetic biology, including SBOL. In this regard, the software provides effective interoperability. The new standard has been tested by experiments and data exchange between Nanyang Technological University in Singapore and Imperial College London.

Synthetic biology between challenges and risks: suggestions for a model of governance and a regulatory framework, based on fundamental rights.

PubMed

Colussi, Ilaria Anna

2013-01-01

This paper deals with the emerging synthetic biology, its challenges and risks, and tries to design a model for the governance and regulation of the field. The model is called of "prudent vigilance" (inspired by the report about synthetic biology, drafted by the U.S. Presidential Commission on Bioethics, 2010), and it entails (a) an ongoing and periodically revised process of assessment and management of all the risks and concerns, and (b) the adoption of policies - taken through "hard law" and "soft law" sources - that are based on the principle of proportionality (among benefits and risks), on a reasonable balancing between different interests and rights at stake, and are oriented by a constitutional frame, which is represented by the protection of fundamental human rights emerging in the field of synthetic biology (right to life, right to health, dignity, freedom of scientific research, right to environment). After the theoretical explanation of the model, its operability is "checked", by considering its application with reference to only one specific risk brought up by synthetic biology - biosecurity risk, i.e. the risk of bioterrorism.

Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project

PubMed Central

Sliva, Anna; Yang, Huanming; Boeke, Jef D.; Mathews, Debra J. H.

2015-01-01

First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) Project is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with this field of research and operate under a common set of principles. In this commentary, we survey the current ethics and regulatory landscape of synthetic biology and present the Sc2.0 Statement of Ethics and Governance to which all members of the project adhere. This statement focuses on four aspects of the Sc2.0 Project: societal benefit, intellectual property, safety, and self-governance. We propose that such project-level agreements are an important, valuable, and flexible model of self-regulation for similar global, large-scale synthetic biology projects in order to maximize the benefits and minimize potential harms. PMID:26272997

Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project.

PubMed

Sliva, Anna; Yang, Huanming; Boeke, Jef D; Mathews, Debra J H

2015-08-01

First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) PROJECT is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with this field of research and operate under a common set of principles. In this commentary, we survey the current ethics and regulatory landscape of synthetic biology and present the Sc2.0 Statement of Ethics and Governance to which all members of the project adhere. This statement focuses on four aspects of the Sc2.0 PROJECT: societal benefit, intellectual property, safety, and self-governance. We propose that such project-level agreements are an important, valuable, and flexible model of self-regulation for similar global, large-scale synthetic biology projects in order to maximize the benefits and minimize potential harms. Copyright © 2015 by the Genetics Society of America.

Synthetic Biology: Knowledge Accessed by Everyone (Open Sources)

ERIC Educational Resources Information Center

Sánchez Reyes, Patricia Margarita

2016-01-01

Using the principles of biology, along with engineering and with the help of computer, scientists manage to copy. DNA sequences from nature and use them to create new organisms. DNA is created through engineering and computer science managing to create life inside a laboratory. We cannot dismiss the role that synthetic biology could lead in…

Application of synthetic biology for production of chemicals in yeast Saccharomyces cerevisiae.

PubMed

Li, Mingji; Borodina, Irina

2015-02-01

Synthetic biology and metabolic engineering enable generation of novel cell factories that efficiently convert renewable feedstocks into biofuels, bulk, and fine chemicals, thus creating the basis for biosustainable economy independent on fossil resources. While over a hundred proof-of-concept chemicals have been made in yeast, only a very small fraction of those has reached commercial-scale production so far. The limiting factor is the high research cost associated with the development of a robust cell factory that can produce the desired chemical at high titer, rate, and yield. Synthetic biology has the potential to bring down this cost by improving our ability to predictably engineer biological systems. This review highlights synthetic biology applications for design, assembly, and optimization of non-native biochemical pathways in baker's yeast Saccharomyces cerevisiae We describe computational tools for the prediction of biochemical pathways, molecular biology methods for assembly of DNA parts into pathways, and for introducing the pathways into the host, and finally approaches for optimizing performance of the introduced pathways. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Standardization in synthetic biology: an engineering discipline coming of age.

PubMed

Decoene, Thomas; De Paepe, Brecht; Maertens, Jo; Coussement, Pieter; Peters, Gert; De Maeseneire, Sofie L; De Mey, Marjan

2018-08-01

Leaping DNA read-and-write technologies, and extensive automation and miniaturization are radically transforming the field of biological experimentation by providing the tools that enable the cost-effective high-throughput required to address the enormous complexity of biological systems. However, standardization of the synthetic biology workflow has not kept abreast with dwindling technical and resource constraints, leading, for example, to the collection of multi-level and multi-omics large data sets that end up disconnected or remain under- or even unexploited. In this contribution, we critically evaluate the various efforts, and the (limited) success thereof, in order to introduce standards for defining, designing, assembling, characterizing, and sharing synthetic biology parts. The causes for this success or the lack thereof, as well as possible solutions to overcome these, are discussed. Akin to other engineering disciplines, extensive standardization will undoubtedly speed-up and reduce the cost of bioprocess development. In this respect, further implementation of synthetic biology standards will be crucial for the field in order to redeem its promise, i.e. to enable predictable forward engineering.

Synthetic biology: navigating the challenges ahead.

PubMed

Bhutkar, Arjun

2005-01-01

The emerging field of synthetic biology is broadly defined as the area of intersection of biology and engineering that focuses on the modification or creation of novel biological systems that do not have a counterpart in nature. Potential applications of this technology range from creating systems for environmental cleanup tasks, for medical diagnosis and treatment, to economical generation of hydrogen fuel. This technology is in tis nascent state and there are a number of concerns surrounding its potential applications and the nature of research being performed. With the potential to create hitherto unknown "living organisms", it raises a number of challenges along different dimensions. This article reviews the current state of the technology and analyzes synthetic biology using different lenses: patentability, ethics, and regulation. It proposes a classification system for the products of synthetic biology and provides recommendations in each of the above areas (patentability, ethics, and regulation) in the context of this classification system. These recommendations include an improved framework for patentability testing, ethical principles to guide work in this area, a controlled approval process, and reference frameworks for regulation.

A standard-enabled workflow for synthetic biology.

PubMed

Myers, Chris J; Beal, Jacob; Gorochowski, Thomas E; Kuwahara, Hiroyuki; Madsen, Curtis; McLaughlin, James Alastair; Mısırlı, Göksel; Nguyen, Tramy; Oberortner, Ernst; Samineni, Meher; Wipat, Anil; Zhang, Michael; Zundel, Zach

2017-06-15

A synthetic biology workflow is composed of data repositories that provide information about genetic parts, sequence-level design tools to compose these parts into circuits, visualization tools to depict these designs, genetic design tools to select parts to create systems, and modeling and simulation tools to evaluate alternative design choices. Data standards enable the ready exchange of information within such a workflow, allowing repositories and tools to be connected from a diversity of sources. The present paper describes one such workflow that utilizes, among others, the Synthetic Biology Open Language (SBOL) to describe genetic designs, the Systems Biology Markup Language to model these designs, and SBOL Visual to visualize these designs. We describe how a standard-enabled workflow can be used to produce types of design information, including multiple repositories and software tools exchanging information using a variety of data standards. Recently, the ACS Synthetic Biology journal has recommended the use of SBOL in their publications. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Multiple particle tracking in 3-D+t microscopy: method and application to the tracking of endocytosed quantum dots.

PubMed

Genovesio, Auguste; Liedl, Tim; Emiliani, Valentina; Parak, Wolfgang J; Coppey-Moisan, Maité; Olivo-Marin, Jean-Christophe

2006-05-01

We propose a method to detect and track multiple moving biological spot-like particles showing different kinds of dynamics in image sequences acquired through multidimensional fluorescence microscopy. It enables the extraction and analysis of information such as number, position, speed, movement, and diffusion phases of, e.g., endosomal particles. The method consists of several stages. After a detection stage performed by a three-dimensional (3-D) undecimated wavelet transform, we compute, for each detected spot, several predictions of its future state in the next frame. This is accomplished thanks to an interacting multiple model (IMM) algorithm which includes several models corresponding to different biologically realistic movement types. Tracks are constructed, thereafter, by a data association algorithm based on the maximization of the likelihood of each IMM. The last stage consists of updating the IMM filters in order to compute final estimations for the present image and to improve predictions for the next image. The performances of the method are validated on synthetic image data and used to characterize the 3-D movement of endocytic vesicles containing quantum dots.

Human Organ Culture: Updating the Approach to Bridge the Gap from In Vitro to In Vivo in Inflammation, Cancer, and Stem Cell Biology.

PubMed

Al-Lamki, Rafia S; Bradley, John R; Pober, Jordan S

2017-01-01

Human studies, critical for developing new diagnostics and therapeutics, are limited by ethical and logistical issues, and preclinical animal studies are often poor predictors of human responses. Standard human cell cultures can address some of these concerns but the absence of the normal tissue microenvironment can alter cellular responses. Three-dimensional cultures that position cells on synthetic matrices, or organoid or organ-on-a-chip cultures, in which different cell spontaneously organize contacts with other cells and natural matrix only partly overcome this limitation. Here, we review how human organ cultures (HOCs) can more faithfully preserve in vivo tissue architecture and can better represent disease-associated changes. We will specifically describe how HOCs can be combined with both traditional and more modern morphological techniques to reveal how anatomic location can alter cellular responses at a molecular level and permit comparisons among different cells and different cell types within the same tissue. Examples are provided involving use of HOCs to study inflammation, cancer, and stem cell biology.

Human Organ Culture: Updating the Approach to Bridge the Gap from In Vitro to In Vivo in Inflammation, Cancer, and Stem Cell Biology

PubMed Central

Al-Lamki, Rafia S.; Bradley, John R.; Pober, Jordan S.

2017-01-01

Human studies, critical for developing new diagnostics and therapeutics, are limited by ethical and logistical issues, and preclinical animal studies are often poor predictors of human responses. Standard human cell cultures can address some of these concerns but the absence of the normal tissue microenvironment can alter cellular responses. Three-dimensional cultures that position cells on synthetic matrices, or organoid or organ-on-a-chip cultures, in which different cell spontaneously organize contacts with other cells and natural matrix only partly overcome this limitation. Here, we review how human organ cultures (HOCs) can more faithfully preserve in vivo tissue architecture and can better represent disease-associated changes. We will specifically describe how HOCs can be combined with both traditional and more modern morphological techniques to reveal how anatomic location can alter cellular responses at a molecular level and permit comparisons among different cells and different cell types within the same tissue. Examples are provided involving use of HOCs to study inflammation, cancer, and stem cell biology. PMID:28955710

Design of a prototype flow microreactor for synthetic biology in vitro.

PubMed

Boehm, Christian R; Freemont, Paul S; Ces, Oscar

2013-09-07

As a reference platform for in vitro synthetic biology, we have developed a prototype flow microreactor for enzymatic biosynthesis. We report the design, implementation, and computer-aided optimisation of a three-step model pathway within a microfluidic reactor. A packed bed format was shown to be optimal for enzyme compartmentalisation after experimental evaluation of several approaches. The specific substrate conversion efficiency could significantly be improved by an optimised parameter set obtained by computational modelling. Our microreactor design provides a platform to explore new in vitro synthetic biology solutions for industrial biosynthesis.

New Synthetic Methods for Hypericum Natural Products

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

Jeon, Insik

Organic chemistry has served as a solid foundation for interdisciplinary research areas, such as molecular biology and medicinal chemistry. An understanding of the biological activities and structural elucidations of natural products can lead to the development of clinically valuable therapeutic options. The advancements of modern synthetic methodologies allow for more elaborate and concise natural product syntheses. The theme of this study centers on the synthesis of natural products with particularly challenging structures and interesting biological activities. The synthetic expertise developed here will be applicable to analog syntheses and to other research problems.

75 FR 66378 - Public Meeting of the Presidential Commission for the Study of Bioethical Issues

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-28

... of synthetic biology, including its potential benefits and risks, and appropriate ethical boundaries... science of synthetic biology, the challenges and risks, and the ethical boundaries that may be important...

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

Leaf LIMS: A Flexible Laboratory Information Management System with a Synthetic Biology Focus.

PubMed

Craig, Thomas; Holland, Richard; D'Amore, Rosalinda; Johnson, James R; McCue, Hannah V; West, Anthony; Zulkower, Valentin; Tekotte, Hille; Cai, Yizhi; Swan, Daniel; Davey, Robert P; Hertz-Fowler, Christiane; Hall, Anthony; Caddick, Mark

2017-12-15

This paper presents Leaf LIMS, a flexible laboratory information management system (LIMS) designed to address the complexity of synthetic biology workflows. At the project's inception there was a lack of a LIMS designed specifically to address synthetic biology processes, with most systems focused on either next generation sequencing or biobanks and clinical sample handling. Leaf LIMS implements integrated project, item, and laboratory stock tracking, offering complete sample and construct genealogy, materials and lot tracking, and modular assay data capture. Hence, it enables highly configurable task-based workflows and supports data capture from project inception to completion. As such, in addition to it supporting synthetic biology it is ideal for many laboratory environments with multiple projects and users. The system is deployed as a web application through Docker and is provided under a permissive MIT license. It is freely available for download at https://leaflims.github.io .

Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities.

PubMed

Roybal, Kole T; Lim, Wendell A

2017-04-26

The ability of immune cells to survey tissues and sense pathologic insults and deviations makes them a unique platform for interfacing with the body and disease. With the rapid advancement of synthetic biology, we can now engineer and equip immune cells with new sensors and controllable therapeutic response programs to sense and treat diseases that our natural immune system cannot normally handle. Here we review the current state of engineered immune cell therapeutics and their unique capabilities compared to small molecules and biologics. We then discuss how engineered immune cells are being designed to combat cancer, focusing on how new synthetic biology tools are providing potential ways to overcome the major roadblocks for treatment. Finally, we give a long-term vision for the use of synthetic biology to engineer immune cells as a general sensor-response platform to precisely detect disease, to remodel disease microenvironments, and to treat a potentially wide range of challenging diseases.

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.

[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.

Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities

PubMed Central

Roybal, Kole T.; Lim, Wendell A.

2017-01-01

The ability of immune cells to survey tissues and sense pathologic insults and deviations makes them a unique platform for interfacing with the body and disease. With the rapid advancement of synthetic biology, we can now engineer and equip immune cells with new sensors and controllable therapeutic response programs to sense and treat diseases that our natural immune system cannot normally handle. Here we review the current state of engineered immune cell therapeutics and their unique capabilities compared to small molecules and biologics. We then discuss how engineered immune cells are being designed to combat cancer, focusing on how new synthetic biology tools are providing potential ways to overcome the major roadblocks for treatment. Finally, we give a long-term vision for the use of synthetic biology to engineer immune cells as a general sensor-response platform to precisely detect disease, to remodel disease microenvironments, and to treat a potentially wide range of challenging diseases. PMID:28446063

Controlled polymer synthesis--from biomimicry towards synthetic biology.

PubMed

Pasparakis, George; Krasnogor, Natalio; Cronin, Leroy; Davis, Benjamin G; Alexander, Cameron

2010-01-01

The controlled assembly of synthetic polymer structures is now possible with an unprecedented range of functional groups and molecular architectures. In this critical review we consider how the ability to create artificial materials over lengthscales ranging from a few nm to several microns is generating systems that not only begin to mimic those in nature but also may lead to exciting applications in synthetic biology (139 references).

Programming languages for synthetic biology.

PubMed

Umesh, P; Naveen, F; Rao, Chanchala Uma Maheswara; Nair, Achuthsankar S

2010-12-01

In the backdrop of accelerated efforts for creating synthetic organisms, the nature and scope of an ideal programming language for scripting synthetic organism in-silico has been receiving increasing attention. A few programming languages for synthetic biology capable of defining, constructing, networking, editing and delivering genome scale models of cellular processes have been recently attempted. All these represent important points in a spectrum of possibilities. This paper introduces Kera, a state of the art programming language for synthetic biology which is arguably ahead of similar languages or tools such as GEC, Antimony and GenoCAD. Kera is a full-fledged object oriented programming language which is tempered by biopart rule library named Samhita which captures the knowledge regarding the interaction of genome components and catalytic molecules. Prominent feature of the language are demonstrated through a toy example and the road map for the future development of Kera is also presented.

Synthetic biology approaches: Towards sustainable exploitation of marine bioactive molecules.

PubMed

Seghal Kiran, G; Ramasamy, Pasiyappazham; Sekar, Sivasankari; Ramu, Meenatchi; Hassan, Saqib; Ninawe, A S; Selvin, Joseph

2018-06-01

The discovery of genes responsible for the production of bioactive metabolites via metabolic pathways combined with the advances in synthetic biology tools, has allowed the establishment of numerous microbial cell factories, for instance the yeast cell factories, for the manufacture of highly useful metabolites from renewable biomass. Genome mining and metagenomics are two platforms provide base-line data for reconstruction of genomes and metabolomes which is based in the development of synthetic/semi-synthetic genomes for marine natural products discovery. Engineered biofilms are being innovated on synthetic biology platform using genetic circuits and cell signalling systems as represillators controlling biofilm formation. Recombineering is a process of homologous recombination mediated genetic engineering, includes insertion, deletion or modification of any sequence specifically. Although this discipline considered new to the scientific domain, this field has now developed as promising endeavor on the accomplishment of sustainable exploitation of marine natural products. Copyright © 2018 Elsevier B.V. All rights reserved.

Is It Time for Synthetic Biodiversity Conservation?

PubMed

Piaggio, Antoinette J; Segelbacher, Gernot; Seddon, Philip J; Alphey, Luke; Bennett, Elizabeth L; Carlson, Robert H; Friedman, Robert M; Kanavy, Dona; Phelan, Ryan; Redford, Kent H; Rosales, Marina; Slobodian, Lydia; Wheeler, Keith

2017-02-01

Evidence indicates that, despite some critical successes, current conservation approaches are not slowing the overall rate of biodiversity loss. The field of synthetic biology, which is capable of altering natural genomes with extremely precise editing, might offer the potential to resolve some intractable conservation problems (e.g., invasive species or pathogens). However, it is our opinion that there has been insufficient engagement by the conservation community with practitioners of synthetic biology. We contend that rapid, large-scale engagement of these two communities is urgently needed to avoid unintended and deleterious ecological consequences. To this point we describe case studies where synthetic biology is currently being applied to conservation, and we highlight the benefits to conservation biologists from engaging with this emerging technology. Published by Elsevier Ltd.

Synthetic biology meets tissue engineering.

PubMed

Davies, Jamie A; Cachat, Elise

2016-06-15

Classical tissue engineering is aimed mainly at producing anatomically and physiologically realistic replacements for normal human tissues. It is done either by encouraging cellular colonization of manufactured matrices or cellular recolonization of decellularized natural extracellular matrices from donor organs, or by allowing cells to self-organize into organs as they do during fetal life. For repair of normal bodies, this will be adequate but there are reasons for making unusual, non-evolved tissues (repair of unusual bodies, interface to electromechanical prostheses, incorporating living cells into life-support machines). Synthetic biology is aimed mainly at engineering cells so that they can perform custom functions: applying synthetic biological approaches to tissue engineering may be one way of engineering custom structures. In this article, we outline the 'embryological cycle' of patterning, differentiation and morphogenesis and review progress that has been made in constructing synthetic biological systems to reproduce these processes in new ways. The state-of-the-art remains a long way from making truly synthetic tissues, but there are now at least foundations for future work. © 2016 Authors; published by Portland Press Limited.

A biochemical network can control formation of a synthetic material by sensing numerous specific stimuli

NASA Astrophysics Data System (ADS)

Hun Yeon, Ju; Chan, Karen Y. T.; Wong, Ting-Chia; Chan, Kelvin; Sutherland, Michael R.; Ismagilov, Rustem F.; Pryzdial, Edward L. G.; Kastrup, Christian J.

2015-05-01

Developing bio-compatible smart materials that assemble in response to environmental cues requires strategies that can discriminate multiple specific stimuli in a complex milieu. Synthetic materials have yet to achieve this level of sensitivity, which would emulate the highly evolved and tailored reaction networks of complex biological systems. Here we show that the output of a naturally occurring network can be replaced with a synthetic material. Exploiting the blood coagulation system as an exquisite biological sensor, the fibrin clot end-product was replaced with a synthetic material under the biological control of a precisely regulated cross-linking enzyme. The functions of the coagulation network remained intact when the material was incorporated. Clot-like polymerization was induced in indirect response to distinct small molecules, phospholipids, enzymes, cells, viruses, an inorganic solid, a polyphenol, a polysaccharide, and a membrane protein. This strategy demonstrates for the first time that an existing stimulus-responsive biological network can be used to control the formation of a synthetic material by diverse classes of physiological triggers.

Induction of interleukin 1 by synthetic and naturally occurring muramyl peptides.

PubMed

Dinarello, C A; Krueger, J M

1986-10-01

Like bacterial lipopolysaccharides (endotoxins), synthetic muramyl peptides (MPs) are thought to exert many of their biological effects by inducing the production of various mediators from host cells. Both synthetic muramyl dipeptide (MDP) and naturally occurring sleep factor (SF), which contains an MP structure, stimulate human monocytes to produce interleukin 1 (IL 1). IL 1 is a family of unique polypeptides that mediate a variety of host defense functions and possess several biological properties, many of which are shared with MPs. Endotoxins are potent inducers of IL 1, but polymyxin B, which blocks endotoxin's biological activities, has no effect on MP-induced IL 1 production. SF purified from human urine and SF isolated from the peritoneal fluid of patients undergoing chronic ambulatory peritoneal dialysis (CAPD) induce IL 1 when incubated with human mononuclear cells in vitro. SF from urine or CAPD fluid induces IL 1 production in the picrogram per milliliter range whereas synthetic MDP requires microgram per milliliter concentrations. Thus, both synthetic and naturally occurring MPs exert their biological effects, in part, by inducing IL 1.

Negotiating the dynamics of uncomfortable knowledge: The case of dual use and synthetic biology

PubMed Central

Marris, Claire; Jefferson, Catherine; Lentzos, Filippa

2014-01-01

Institutions need to ignore some knowledge in order to function. This is “uncomfortable knowledge” because it undermines the ability of those institutions to pursue their goals (Rayner, 2012). We identify three bodies of knowledge that are relevant to understandings of the dual use threat posed by synthetic biology but are excluded from related policy discussions. We demonstrate how these “unknown knowns” constitute uncomfortable knowledge because they disrupt the simplified worldview that underpins contemporary discourse on the potential misuse of synthetic biology by malign actors. We describe how these inconvenient truths have been systematically ignored and argue that this is because they are perceived as a threat by organisations involved in the promotion of synthetic biology as well as by those involved in managing biosecurity risks. This has led to a situation where concerns about the biosecurity threat posed by synthetic biology are not only exaggerated, but are, more importantly, misplaced. This, in turn, means that related policies are misdirected and unlikely to have much impact. We focus on the dynamics of discussions about synthetic biology and dual use to demonstrate how the same “knowns” that are denied or dismissed as “unknown knowns” in certain circumstances are sometimes mobilised as “known knowns” by the same category of actors in a different context, when this serves to sustain the goals of the individuals and institutions involved. Based on our own experience, we argue that negotiating the dynamics of uncomfortable knowledge is a difficult, but necessary, component of meaningful transdisciplinary collaborations. PMID:25484910

[How to be prudent with synthetic biology. Synthetic Biology and the precautionary principle].

PubMed

Rodríguez López, Blanca

2014-01-01

Synthetic biology is a new discipline that is twofold: firstly it offers the promise to pay benefits that can alleviate some of the ills that plague mankind; On the other hand, like all technologies, holds risks. Given these, the most critical and concerned about the risks, invoke the application of the precautionary principle, common in cases where an activity or new technology creates risks to the environment and/or human health, but far from universally accepted happens to be currently one of the most controversial principles. In this paper the question of the risks and benefits of synthetic biology and the relevance of applying the precautionary principle are analyzed. To do this we proceed as follows. The first part focuses on synthetic biology. At first, this discipline is characterized, with special attention to what is novel compared to the known as "genetic engineering". In the second stage both the benefits and the risks associated with it are discussed. The first part concludes with a review of the efforts currently being made to control or minimize the risks. The second part aims to analyze the precautionary principle and its possible relevance to the case of Synthetic Biology. At first, the different versions and interpretations of the principle and the various criticisms of which has been the subject are reviewed. Finally, after discarding the Precautionary Principle as an useful tool, it is seen as more appropriate some recent proposals to treat technologies that take into account not only risks but also their benefits.

Renewable Energy from Synthetic Biology (LBNL Science at the Theater)

ScienceCinema

Keasling, Jay [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2018-05-25

Jay Keasling, co-leader of Berkeley Lab's Helios Project, is a groundbreaking researcher in the new scientific field of synthetic biology. In Helios, he directs the biology program, incorporating a range of approaches to increasing the efficacy and economy of plants and cellulose-degrading microbes to make solar-based fuels. He is a UC Berkeley professor of Chemical and Bioengineering, and founder of Amyris Biotechnologies, a company that was honored as a Technology Pioneer for 2006 by the World Economic Forum. Keasling has succeeded in using synthetic biology to develop a yeast-based production scheme for precursors of the antimalarial drug artemisinin in work funded by the Bill & Melinda Gates Foundation.

Renewable Energy from Synthetic Biology (LBNL Science at the Theater)

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

Keasling, Jay

2007-06-04

Jay Keasling, co-leader of Berkeley Lab's Helios Project, is a groundbreaking researcher in the new scientific field of synthetic biology. In Helios, he directs the biology program, incorporating a range of approaches to increasing the efficacy and economy of plants and cellulose-degrading microbes to make solar-based fuels. He is a UC Berkeley professor of Chemical and Bioengineering, and founder of Amyris Biotechnologies, a company that was honored as a Technology Pioneer for 2006 by the World Economic Forum. Keasling has succeeded in using synthetic biology to develop a yeast-based production scheme for precursors of the antimalarial drug artemisinin in workmore » funded by the Bill & Melinda Gates Foundation.« less

Synthetic biology expands chemical control of microorganisms.

PubMed

Ford, Tyler J; Silver, Pamela A

2015-10-01

The tools of synthetic biology allow researchers to change the ways engineered organisms respond to chemical stimuli. Decades of basic biology research and new efforts in computational protein and RNA design have led to the development of small molecule sensors that can be used to alter organism function. These new functions leap beyond the natural propensities of the engineered organisms. They can range from simple fluorescence or growth reporting to pathogen killing, and can involve metabolic coordination among multiple cells or organisms. Herein, we discuss how synthetic biology alters microorganisms' responses to chemical stimuli resulting in the development of microbes as toxicity sensors, disease treatments, and chemical factories. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthetic Analog and Digital Circuits for Cellular Computation and Memory

PubMed Central

Purcell, Oliver; Lu, Timothy K.

2014-01-01

Biological computation is a major area of focus in synthetic biology because it has the potential to enable a wide range of applications. Synthetic biologists have applied engineering concepts to biological systems in order to construct progressively more complex gene circuits capable of processing information in living cells. Here, we review the current state of computational genetic circuits and describe artificial gene circuits that perform digital and analog computation. We then discuss recent progress in designing gene circuits that exhibit memory, and how memory and computation have been integrated to yield more complex systems that can both process and record information. Finally, we suggest new directions for engineering biological circuits capable of computation. PMID:24794536

Cosmo Cassette: A Microfluidic Microgravity Microbial System For Synthetic Biology Unit Tests and Satellite Missions

NASA Technical Reports Server (NTRS)

Berliner, Aaron J.

2013-01-01

Although methods in the design-build-test life cycle of the synthetic biology field have grown rapidly, the expansion has been non-uniform. The design and build stages in development have seen innovations in the form of biological CAD and more efficient means for building DNA, RNA, and other biological constructs. The testing phase of the cycle remains in need of innovation. Presented will be both a theoretical abstraction of biological measurement and a practical demonstration of a microfluidics-based platform for characterizing synthetic biological phenomena. Such a platform demonstrates a design of additive manufacturing (3D printing) for construction of a microbial fuel cell (MFC) to be used in experiments carried out in space. First, the biocompatibility of the polypropylene chassis will be demonstrated. The novel MFCs will be cheaper, and faster to make and iterate through designs. The novel design will contain a manifold switchingdistribution system and an integrated in-chip set of reagent reservoirs fabricated via 3D printing. The automated nature of the 3D printing yields itself to higher resolution switching valves and leads to smaller sized payloads, lower cost, reduced power and a standardized platform for synthetic biology unit tests on Earth and in space. It will be demonstrated that the application of unit testing in synthetic biology will lead to the automatic construction and validation of desired constructs. Unit testing methodologies offer benefits of preemptive problem identification, change of facility, simplicity of integration, ease of documentation, and separation of interface from implementation, and automated design.

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.

Synthetic Astrobiology

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2016-01-01

Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. And what about the limits for life? Can we create organisms that expand the envelope for life? In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

Droplet microfluidics for synthetic biology

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

Gach, Philip Charles; Iwai, Kosuke; Kim, Peter Wonhee

Here, synthetic biology is an interdisciplinary field that aims to engineer biological systems for useful purposes. Organism engineering often requires the optimization of individual genes and/or entire biological pathways (consisting of multiple genes). Advances in DNA sequencing and synthesis have recently begun to enable the possibility of evaluating thousands of gene variants and hundreds of thousands of gene combinations. However, such large-scale optimization experiments remain cost-prohibitive to researchers following traditional molecular biology practices, which are frequently labor-intensive and suffer from poor reproducibility. Liquid handling robotics may reduce labor and improve reproducibility, but are themselves expensive and thus inaccessible to mostmore » researchers. Microfluidic platforms offer a lower entry price point alternative to robotics, and maintain high throughput and reproducibility while further reducing operating costs through diminished reagent volume requirements. Droplet microfluidics have shown exceptional promise for synthetic biology experiments, including DNA assembly, transformation/transfection, culturing, cell sorting, phenotypic assays, artificial cells and genetic circuits.« less

Droplet microfluidics for synthetic biology

DOE PAGES

Gach, Philip Charles; Iwai, Kosuke; Kim, Peter Wonhee; ...

2017-08-10

Here, synthetic biology is an interdisciplinary field that aims to engineer biological systems for useful purposes. Organism engineering often requires the optimization of individual genes and/or entire biological pathways (consisting of multiple genes). Advances in DNA sequencing and synthesis have recently begun to enable the possibility of evaluating thousands of gene variants and hundreds of thousands of gene combinations. However, such large-scale optimization experiments remain cost-prohibitive to researchers following traditional molecular biology practices, which are frequently labor-intensive and suffer from poor reproducibility. Liquid handling robotics may reduce labor and improve reproducibility, but are themselves expensive and thus inaccessible to mostmore » researchers. Microfluidic platforms offer a lower entry price point alternative to robotics, and maintain high throughput and reproducibility while further reducing operating costs through diminished reagent volume requirements. Droplet microfluidics have shown exceptional promise for synthetic biology experiments, including DNA assembly, transformation/transfection, culturing, cell sorting, phenotypic assays, artificial cells and genetic circuits.« less

Synthetic biology and conservation of nature: wicked problems and wicked solutions.

PubMed

Redford, Kent H; Adams, William; Mace, Georgina M

2013-01-01

So far, conservation scientists have paid little attention to synthetic biology; this is unfortunate as the technology is likely to transform the operating space within which conservation functions, and therefore the prospects for maintaining biodiversity into the future.

A life scientist, an engineer and a social scientist walk into a lab: challenges of dual-use engagement and education in synthetic biology.

PubMed

Edwards, Brett; Kelle, Alexander

2012-01-01

The discussion of dual-use education is often predicated on a discrete population of practicing life scientists exhibiting certain deficiencies in awareness or expertise. This has lead to the claim that there is a greater requirement for awareness raising and education amongst this population. However, there is yet to be an inquiry into the impact of the 'convergent' nature of emerging techno-sciences upon the prospects of dual-use education. The field of synthetic biology, although often portrayed as homogeneous, is in fact composed of various sub-fields and communities. Its practitioners have diverse academic backgrounds. The research institutions that have fostered its development in the UK often have their own sets of norms and practices in engagement with ethical, legal and social issues associated with scientific knowledge and technologies. The area is also complicated by the emergence of synthetic biologists outside traditional research environments, the so called 'do-it-yourself' or 'garage biologists'. This paper untangles some of the complexities in the current state of synthetic biology and addresses the prospects for dual-use education for practitioners. It provides a short overview of the field and discusses identified dual-use issues. There follows a discussion of UK networks in synthetic biology, including their engagement with ethical, legal, social and dual-use issues and limited educational efforts in relation to these. It concludes by outlining options for developing a more systematic dual-use education strategy for synthetic biology.

Cooperativity to increase Turing pattern space for synthetic biology.

PubMed

Diambra, Luis; Senthivel, Vivek Raj; Menendez, Diego Barcena; Isalan, Mark

2015-02-20

It is hard to bridge the gap between mathematical formulations and biological implementations of Turing patterns, yet this is necessary for both understanding and engineering these networks with synthetic biology approaches. Here, we model a reaction-diffusion system with two morphogens in a monostable regime, inspired by components that we recently described in a synthetic biology study in mammalian cells.1 The model employs a single promoter to express both the activator and inhibitor genes and produces Turing patterns over large regions of parameter space, using biologically interpretable Hill function reactions. We applied a stability analysis and identified rules for choosing biologically tunable parameter relationships to increase the likelihood of successful patterning. We show how to control Turing pattern sizes and time evolution by manipulating the values for production and degradation relationships. More importantly, our analysis predicts that steep dose-response functions arising from cooperativity are mandatory for Turing patterns. Greater steepness increases parameter space and even reduces the requirement for differential diffusion between activator and inhibitor. These results demonstrate some of the limitations of linear scenarios for reaction-diffusion systems and will help to guide projects to engineer synthetic Turing patterns.

Synthetic Modifications In the Frequency Domain for Finite Element Model Update and Damage Detection

DTIC Science & Technology

2017-09-01

Sensitivity-based finite element model updating and structural damage detection has been limited by the number of modes available in a vibration test and...increase the number of modes and corresponding sensitivity data by artificially constraining the structure under test, producing a large number of... structural modifications to the measured data, including both springs-to-ground and mass modifications. This is accomplished with frequency domain

Synthetic Morphogenesis.

PubMed

Teague, Brian P; Guye, Patrick; Weiss, Ron

2016-09-01

Throughout biology, function is intimately linked with form. Across scales ranging from subcellular to multiorganismal, the identity and organization of a biological structure's subunits dictate its properties. The field of molecular morphogenesis has traditionally been concerned with describing these links, decoding the molecular mechanisms that give rise to the shape and structure of cells, tissues, organs, and organisms. Recent advances in synthetic biology promise unprecedented control over these molecular mechanisms; this opens the path to not just probing morphogenesis but directing it. This review explores several frontiers in the nascent field of synthetic morphogenesis, including programmable tissues and organs, synthetic biomaterials and programmable matter, and engineering complex morphogenic systems de novo. We will discuss each frontier's objectives, current approaches, constraints and challenges, and future potential. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

Designing Uniquely Addressable Bio-orthogonal Synthetic Scaffolds for DNA and RNA Origami.

PubMed

Kozyra, Jerzy; Ceccarelli, Alessandro; Torelli, Emanuela; Lopiccolo, Annunziata; Gu, Jing-Ying; Fellermann, Harold; Stimming, Ulrich; Krasnogor, Natalio

2017-07-21

Nanotechnology and synthetic biology are rapidly converging, with DNA origami being one of the leading bridging technologies. DNA origami was shown to work well in a wide array of biotic environments. However, the large majority of extant DNA origami scaffolds utilize bacteriophages or plasmid sequences thus severely limiting its future applicability as a bio-orthogonal nanotechnology platform. In this paper we present the design of biologically inert (i.e., "bio-orthogonal") origami scaffolds. The synthetic scaffolds have the additional advantage of being uniquely addressable (unlike biologically derived ones) and hence are better optimized for high-yield folding. We demonstrate our fully synthetic scaffold design with both DNA and RNA origamis and describe a protocol to produce these bio-orthogonal and uniquely addressable origami scaffolds.

Rewiring cells: synthetic biology as a tool to interrogate the organizational principles of living systems.

PubMed

Bashor, Caleb J; Horwitz, Andrew A; Peisajovich, Sergio G; Lim, Wendell A

2010-01-01

The living cell is an incredibly complex entity, and the goal of predictively and quantitatively understanding its function is one of the next great challenges in biology. Much of what we know about the cell concerns its constituent parts, but to a great extent we have yet to decode how these parts are organized to yield complex physiological function. Classically, we have learned about the organization of cellular networks by disrupting them through genetic or chemical means. The emerging discipline of synthetic biology offers an additional, powerful approach to study systems. By rearranging the parts that comprise existing networks, we can gain valuable insight into the hierarchical logic of the networks and identify the modular building blocks that evolution uses to generate innovative function. In addition, by building minimal toy networks, one can systematically explore the relationship between network structure and function. Here, we outline recent work that uses synthetic biology approaches to investigate the organization and function of cellular networks, and describe a vision for a synthetic biology toolkit that could be used to interrogate the design principles of diverse systems.

Control theory meets synthetic biology

PubMed Central

2016-01-01

The past several years have witnessed an increased presence of control theoretic concepts in synthetic biology. This review presents an organized summary of how these control design concepts have been applied to tackle a variety of problems faced when building synthetic biomolecular circuits in living cells. In particular, we describe success stories that demonstrate how simple or more elaborate control design methods can be used to make the behaviour of synthetic genetic circuits within a single cell or across a cell population more reliable, predictable and robust to perturbations. The description especially highlights technical challenges that uniquely arise from the need to implement control designs within a new hardware setting, along with implemented or proposed solutions. Some engineering solutions employing complex feedback control schemes are also described, which, however, still require a deeper theoretical analysis of stability, performance and robustness properties. Overall, this paper should help synthetic biologists become familiar with feedback control concepts as they can be used in their application area. At the same time, it should provide some domain knowledge to control theorists who wish to enter the rising and exciting field of synthetic biology. PMID:27440256

Control theory meets synthetic biology.

PubMed

Del Vecchio, Domitilla; Dy, Aaron J; Qian, Yili

2016-07-01

The past several years have witnessed an increased presence of control theoretic concepts in synthetic biology. This review presents an organized summary of how these control design concepts have been applied to tackle a variety of problems faced when building synthetic biomolecular circuits in living cells. In particular, we describe success stories that demonstrate how simple or more elaborate control design methods can be used to make the behaviour of synthetic genetic circuits within a single cell or across a cell population more reliable, predictable and robust to perturbations. The description especially highlights technical challenges that uniquely arise from the need to implement control designs within a new hardware setting, along with implemented or proposed solutions. Some engineering solutions employing complex feedback control schemes are also described, which, however, still require a deeper theoretical analysis of stability, performance and robustness properties. Overall, this paper should help synthetic biologists become familiar with feedback control concepts as they can be used in their application area. At the same time, it should provide some domain knowledge to control theorists who wish to enter the rising and exciting field of synthetic biology. © 2016 The Author(s).

Towards Self-Assembled Hybrid Artificial Cells: Novel Bottom-Up Approaches to Functional Synthetic Membranes

PubMed Central

Brea, Roberto J.; Hardy, Michael D.; Devaraj, Neal K.

2015-01-01

There has been increasing interest in utilizing bottom-up approaches to develop synthetic cells. A popular methodology is the integration of functionalized synthetic membranes with biological systems, producing “hybrid” artificial cells. This Concept article covers recent advances and the current state-of-the-art of such hybrid systems. Specifically, we describe minimal supramolecular constructs that faithfully mimic the structure and/or function of living cells, often by controlling the assembly of highly ordered membrane architectures with defined functionality. These studies give us a deeper understanding of the nature of living systems, bring new insights into the origin of cellular life, and provide novel synthetic chassis for advancing synthetic biology. PMID:26149747

Synthetic analog and digital circuits for cellular computation and memory.

PubMed

Purcell, Oliver; Lu, Timothy K

2014-10-01

Biological computation is a major area of focus in synthetic biology because it has the potential to enable a wide range of applications. Synthetic biologists have applied engineering concepts to biological systems in order to construct progressively more complex gene circuits capable of processing information in living cells. Here, we review the current state of computational genetic circuits and describe artificial gene circuits that perform digital and analog computation. We then discuss recent progress in designing gene networks that exhibit memory, and how memory and computation have been integrated to yield more complex systems that can both process and record information. Finally, we suggest new directions for engineering biological circuits capable of computation. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

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.

[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.

The Next Generation of Synthetic Biology Chassis: Moving Synthetic Biology from the Laboratory to the Field

DTIC Science & Technology

2016-09-26

toolkit of additional promoters, RBS, and proteolysis tags to control gene expression at the transcrip- tional, translational, and protein levels. CRISPR ...synthetic promoters, high efficiency RBS, and terminators. Furthermore, the CRISPR -Cas system has been investigated for one cyanobacteria species,10 which...Development of a CRISPR -Cas9 toolkit for comprehensive engineer- ing of Bacillus subtilis. Appl. Environ. Microbiol. 82, 01159−01116. (9) Hussein, A. H

Data Integration and Mining for Synthetic Biology Design.

PubMed

Mısırlı, Göksel; Hallinan, Jennifer; Pocock, Matthew; Lord, Phillip; McLaughlin, James Alastair; Sauro, Herbert; Wipat, Anil

2016-10-21

One aim of synthetic biologists is to create novel and predictable biological systems from simpler modular parts. This approach is currently hampered by a lack of well-defined and characterized parts and devices. However, there is a wealth of existing biological information, which can be used to identify and characterize biological parts, and their design constraints in the literature and numerous biological databases. However, this information is spread among these databases in many different formats. New computational approaches are required to make this information available in an integrated format that is more amenable to data mining. A tried and tested approach to this problem is to map disparate data sources into a single data set, with common syntax and semantics, to produce a data warehouse or knowledge base. Ontologies have been used extensively in the life sciences, providing this common syntax and semantics as a model for a given biological domain, in a fashion that is amenable to computational analysis and reasoning. Here, we present an ontology for applications in synthetic biology design, SyBiOnt, which facilitates the modeling of information about biological parts and their relationships. SyBiOnt was used to create the SyBiOntKB knowledge base, incorporating and building upon existing life sciences ontologies and standards. The reasoning capabilities of ontologies were then applied to automate the mining of biological parts from this knowledge base. We propose that this approach will be useful to speed up synthetic biology design and ultimately help facilitate the automation of the biological engineering life cycle.

Inference of physical/biological dynamics from synthetic ocean colour images

NASA Technical Reports Server (NTRS)

Eert, J.; Holloway, G.; Gower, J. F. R.; Denman, K.; Abbott, M.

1987-01-01

High resolution numerical experiments with well resolved eddies are performed including advection of a biologically active plankton field. Shelf wave propagation and bottom topographic features are included. The resulting synthetic ocean color fields are examined for sensitivity to the (known) underlying physical dynamics.

BISRU: Synthetic Microbes for Moon, Mars and Beyond

NASA Astrophysics Data System (ADS)

Cumbers, J.; Rothchild, L.

2010-04-01

Synthetic biology and genomics will bring a new range of designer organisms into being and give us new tools for the manipulation and control of these organisms. BISRU or biological in situ resource utilization is the use of such genetically modified organisms in space.

Synthetic biology approaches to biological containment: pre-emptively tackling potential risks

PubMed Central

Krüger, Antje; Csibra, Eszter; Gianni, Edoardo

2016-01-01

Biocontainment comprises any strategy applied to ensure that harmful organisms are confined to controlled laboratory conditions and not allowed to escape into the environment. Genetically engineered microorganisms (GEMs), regardless of the nature of the modification and how it was established, have potential human or ecological impact if accidentally leaked or voluntarily released into a natural setting. Although all evidence to date is that GEMs are unable to compete in the environment, the power of synthetic biology to rewrite life requires a pre-emptive strategy to tackle possible unknown risks. Physical containment barriers have proven effective but a number of strategies have been developed to further strengthen biocontainment. Research on complex genetic circuits, lethal genes, alternative nucleic acids, genome recoding and synthetic auxotrophies aim to design more effective routes towards biocontainment. Here, we describe recent advances in synthetic biology that contribute to the ongoing efforts to develop new and improved genetic, semantic, metabolic and mechanistic plans for the containment of GEMs. PMID:27903826

Synthetic biology approaches to biological containment: pre-emptively tackling potential risks.

PubMed

Torres, Leticia; Krüger, Antje; Csibra, Eszter; Gianni, Edoardo; Pinheiro, Vitor B

2016-11-30

Biocontainment comprises any strategy applied to ensure that harmful organisms are confined to controlled laboratory conditions and not allowed to escape into the environment. Genetically engineered microorganisms (GEMs), regardless of the nature of the modification and how it was established, have potential human or ecological impact if accidentally leaked or voluntarily released into a natural setting. Although all evidence to date is that GEMs are unable to compete in the environment, the power of synthetic biology to rewrite life requires a pre-emptive strategy to tackle possible unknown risks. Physical containment barriers have proven effective but a number of strategies have been developed to further strengthen biocontainment. Research on complex genetic circuits, lethal genes, alternative nucleic acids, genome recoding and synthetic auxotrophies aim to design more effective routes towards biocontainment. Here, we describe recent advances in synthetic biology that contribute to the ongoing efforts to develop new and improved genetic, semantic, metabolic and mechanistic plans for the containment of GEMs. © 2016 The Author(s).

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

Synthetic Biology between Self-Regulation and Public Discourse: Ethical Issues and the Many Roles of the Ethicist.

PubMed

Arnason, Gardar

2017-04-01

This article discusses the roles of ethicists in the governance of synthetic biology. I am particularly concerned with the idea of self-regulation of bioscience and its relationship to public discourse about ethical issues in bioscience. I will look at the role of philosophical ethicists at different levels and loci, from the "embedded ethicist" in the laboratory or research project, to ethicists' impact on policy and public discourse. In a democratic society, the development of governance frameworks for emerging technologies, such as synthetic biology, needs to be guided by a well-informed public discourse. In the case of synthetic biology, the public discourse has to go further than merely considering technical issues of biosafety and biosecurity, or risk management, to consider more philosophical issues concerning the meaning and value of "life" between the natural and the synthetic. I argue that ethicists have moral expertise to bring to the public arena, which consists not only in guiding the debate but also in evaluating arguments and moral positions and making normative judgments. When ethicists make normative claims or moral judgments, they must be transparent about their theoretical positions and basic moral standpoints.

Synthetic biology for microbial heavy metal biosensors.

PubMed

Kim, Hyun Ju; Jeong, Haeyoung; Lee, Sang Jun

2018-02-01

Using recombinant DNA technology, various whole-cell biosensors have been developed for detection of environmental pollutants, including heavy metal ions. Whole-cell biosensors have several advantages: easy and inexpensive cultivation, multiple assays, and no requirement of any special techniques for analysis. In the era of synthetic biology, cutting-edge DNA sequencing and gene synthesis technologies have accelerated the development of cell-based biosensors. Here, we summarize current technological advances in whole-cell heavy metal biosensors, including the synthetic biological components (bioparts), sensing and reporter modules, genetic circuits, and chassis cells. We discuss several opportunities for improvement of synthetic cell-based biosensors. First, new functional modules must be discovered in genome databases, and this knowledge must be used to upgrade specific bioparts through molecular engineering. Second, modules must be assembled into functional biosystems in chassis cells. Third, heterogeneity of individual cells in the microbial population must be eliminated. In the perspectives, the development of whole-cell biosensors is also discussed in the aspects of cultivation methods and synthetic cells.

Synthetic biology devices and circuits for RNA-based 'smart vaccines': a propositional review.

PubMed

Andries, Oliwia; Kitada, Tasuku; Bodner, Katie; Sanders, Niek N; Weiss, Ron

2015-02-01

Nucleic acid vaccines have been gaining attention as an alternative to the standard attenuated pathogen or protein based vaccine. However, an unrealized advantage of using such DNA or RNA based vaccination modalities is the ability to program within these nucleic acids regulatory devices that would provide an immunologist with the power to control the production of antigens and adjuvants in a desirable manner by administering small molecule drugs as chemical triggers. Advances in synthetic biology have resulted in the creation of highly predictable and modular genetic parts and devices that can be composed into synthetic gene circuits with complex behaviors. With the recent advent of modified RNA gene delivery methods and developments in the RNA replicon platform, we foresee a future in which mammalian synthetic biologists will create genetic circuits encoded exclusively on RNA. Here, we review the current repertoire of devices used in RNA synthetic biology and propose how programmable 'smart vaccines' will revolutionize the field of RNA vaccination.

Marine Microbiological Enzymes: Studies with Multiple Strategies and Prospects.

PubMed

Wang, Yan; Song, Qinghao; Zhang, Xiao-Hua

2016-09-22

Marine microorganisms produce a series of promising enzymes that have been widely used or are potentially valuable for our daily life. Both classic and newly developed biochemistry technologies have been broadly used to study marine and terrestrial microbiological enzymes. In this brief review, we provide a research update and prospects regarding regulatory mechanisms and related strategies of acyl-homoserine lactones (AHL) lactonase, which is an important but largely unexplored enzyme. We also detail the status and catalytic mechanism of the main types of polysaccharide-degrading enzymes that broadly exist among marine microorganisms but have been poorly explored. In order to facilitate understanding, the regulatory and synthetic biology strategies of terrestrial microorganisms are also mentioned in comparison. We anticipate that this review will provide an outline of multiple strategies for promising marine microbial enzymes and open new avenues for the exploration, engineering and application of various enzymes.

Enhancing GADRAS Source Term Inputs for Creation of Synthetic Spectra.

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

Horne, Steven M.; Harding, Lee

The Gamma Detector Response and Analysis Software (GADRAS) team has enhanced the source term input for the creation of synthetic spectra. These enhancements include the following: allowing users to programmatically provide source information to GADRAS through memory, rather than through a string limited to 256 characters; allowing users to provide their own source decay database information; and updating the default GADRAS decay database to fix errors and include coincident gamma information.

Synthetic biology for microbial production of lipid-based biofuels.

PubMed

d'Espaux, Leo; Mendez-Perez, Daniel; Li, Rachel; Keasling, Jay D

2015-12-01

The risks of maintaining current CO2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. We further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential of synthetic biology for sustainable manufacturing. Published by Elsevier Ltd.

Synthetic biology approaches to engineer T cells.

PubMed

Wu, Chia-Yung; Rupp, Levi J; Roybal, Kole T; Lim, Wendell A

2015-08-01

There is rapidly growing interest in learning how to engineer immune cells, such as T lymphocytes, because of the potential of these engineered cells to be used for therapeutic applications such as the recognition and killing of cancer cells. At the same time, our knowhow and capability to logically engineer cellular behavior is growing rapidly with the development of synthetic biology. Here we describe how synthetic biology approaches are being used to rationally alter the behavior of T cells to optimize them for therapeutic functions. We also describe future developments that will be important in order to construct safe and precise T cell therapeutics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Policy on synthetic biology: deliberation, probability, and the precautionary paradox.

PubMed

Wareham, Christopher; Nardini, Cecilia

2015-02-01

Synthetic biology is a cutting-edge area of research that holds the promise of unprecedented health benefits. However, in tandem with these large prospective benefits, synthetic biology projects entail a risk of catastrophic consequences whose severity may exceed that of most ordinary human undertakings. This is due to the peculiar nature of synthetic biology as a 'threshold technology' which opens doors to opportunities and applications that are essentially unpredictable. Fears about these potentially unstoppable consequences have led to declarations from civil society groups calling for the use of a precautionary principle to regulate the field. Moreover, the principle is prevalent in law and international agreements. Despite widespread political recognition of a need for caution, the precautionary principle has been extensively criticized as a guide for regulatory policy. We examine a central objection to the principle: that its application entails crippling inaction and incoherence, since whatever action one takes there is always a chance that some highly improbable cataclysm will occur. In response to this difficulty, which we call the 'precautionary paradox,' we outline a deliberative means for arriving at threshold of probability below which potential dangers can be disregarded. In addition, we describe a Bayesian mechanism with which to assign probabilities to harmful outcomes. We argue that these steps resolve the paradox. The rehabilitated PP can thus provide a viable policy option to confront the uncharted waters of synthetic biology research. © 2013 John Wiley & Sons Ltd.

SYNTHETIC BIOLOGY. Emergent genetic oscillations in a synthetic microbial consortium.

PubMed

Chen, Ye; Kim, Jae Kyoung; Hirning, Andrew J; Josić, Krešimir; Bennett, Matthew R

2015-08-28

A challenge of synthetic biology is the creation of cooperative microbial systems that exhibit population-level behaviors. Such systems use cellular signaling mechanisms to regulate gene expression across multiple cell types. We describe the construction of a synthetic microbial consortium consisting of two distinct cell types—an "activator" strain and a "repressor" strain. These strains produced two orthogonal cell-signaling molecules that regulate gene expression within a synthetic circuit spanning both strains. The two strains generated emergent, population-level oscillations only when cultured together. Certain network topologies of the two-strain circuit were better at maintaining robust oscillations than others. The ability to program population-level dynamics through the genetic engineering of multiple cooperative strains points the way toward engineering complex synthetic tissues and organs with multiple cell types. Copyright © 2015, American Association for the Advancement of Science.

Accessing Nature’s diversity through metabolic engineering and synthetic biology

PubMed Central

King, Jason R.; Edgar, Steven; Qiao, Kangjian; Stephanopoulos, Gregory

2016-01-01

In this perspective, we highlight recent examples and trends in metabolic engineering and synthetic biology that demonstrate the synthetic potential of enzyme and pathway engineering for natural product discovery. In doing so, we introduce natural paradigms of secondary metabolism whereby simple carbon substrates are combined into complex molecules through “scaffold diversification”, and subsequent “derivatization” of these scaffolds is used to synthesize distinct complex natural products. We provide examples in which modern pathway engineering efforts including combinatorial biosynthesis and biological retrosynthesis can be coupled to directed enzyme evolution and rational enzyme engineering to allow access to the “privileged” chemical space of natural products in industry-proven microbes. Finally, we forecast the potential to produce natural product-like discovery platforms in biological systems that are amenable to single-step discovery, validation, and synthesis for streamlined discovery and production of biologically active agents. PMID:27081481

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

Biological interaction of living cells with COSAN-based synthetic vesicles

PubMed Central

Tarrés, Màrius; Canetta, Elisabetta; Paul, Eleanor; Forbes, Jordan; Azzouni, Karima; Viñas, Clara; Teixidor, Francesc; Harwood, Adrian J.

2015-01-01

Cobaltabisdicarbollide (COSAN) [3,3′-Co(1,2-C2B9H11)2]−, is a complex boron-based anion that has the unusual property of self-assembly into membranes and vesicles. These membranes have similar dimensions to biological membranes found in cells, and previously COSAN has been shown to pass through synthetic lipid membranes and those of living cells without causing breakdown of membrane barrier properties. Here, we investigate the interaction of this inorganic membrane system with living cells. We show that COSAN has no immediate effect on cell viability, and cells fully recover when COSAN is removed following exposure for hours to days. COSAN elicits a range of cell biological effects, including altered cell morphology, inhibition of cell growth and, in some cases, apoptosis. These observations reveal a new biology at the interface between inorganic, synthetic COSAN membranes and naturally occurring biological membranes. PMID:25588708

Biological interaction of living cells with COSAN-based synthetic vesicles.

PubMed

Tarrés, Màrius; Canetta, Elisabetta; Paul, Eleanor; Forbes, Jordan; Azzouni, Karima; Viñas, Clara; Teixidor, Francesc; Harwood, Adrian J

2015-01-15

Cobaltabisdicarbollide (COSAN) [3,3'-Co(1,2-C2B9H11)2](-), is a complex boron-based anion that has the unusual property of self-assembly into membranes and vesicles. These membranes have similar dimensions to biological membranes found in cells, and previously COSAN has been shown to pass through synthetic lipid membranes and those of living cells without causing breakdown of membrane barrier properties. Here, we investigate the interaction of this inorganic membrane system with living cells. We show that COSAN has no immediate effect on cell viability, and cells fully recover when COSAN is removed following exposure for hours to days. COSAN elicits a range of cell biological effects, including altered cell morphology, inhibition of cell growth and, in some cases, apoptosis. These observations reveal a new biology at the interface between inorganic, synthetic COSAN membranes and naturally occurring biological membranes.

The Eugene language for synthetic biology.

PubMed

Bilitchenko, Lesia; Liu, Adam; Densmore, Douglas

2011-01-01

Synthetic biological systems are currently created by an ad hoc, iterative process of design, simulation, and assembly. These systems would greatly benefit from the introduction of a more formalized and rigorous specification of the desired system components as well as constraints on their composition. In order to do so, the creation of robust and efficient design flows and tools is imperative. We present a human readable language (Eugene) which allows for both the specification of synthetic biological designs based on biological parts as well as providing a very expressive constraint system to drive the creation of composite devices from collection of parts. This chapter provides an overview of the language primitives as well as instructions on installation and use of Eugene v0.03b. Copyright © 2011 Elsevier Inc. All rights reserved.

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...

Droplet microfluidics for synthetic biology

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

Gach, PC; Iwai, K; Kim, PW

2017-01-01

© 2017 The Royal Society of Chemistry. Synthetic biology is an interdisciplinary field that aims to engineer biological systems for useful purposes. Organism engineering often requires the optimization of individual genes and/or entire biological pathways (consisting of multiple genes). Advances in DNA sequencing and synthesis have recently begun to enable the possibility of evaluating thousands of gene variants and hundreds of thousands of gene combinations. However, such large-scale optimization experiments remain cost-prohibitive to researchers following traditional molecular biology practices, which are frequently labor-intensive and suffer from poor reproducibility. Liquid handling robotics may reduce labor and improve reproducibility, but are themselvesmore » expensive and thus inaccessible to most researchers. Microfluidic platforms offer a lower entry price point alternative to robotics, and maintain high throughput and reproducibility while further reducing operating costs through diminished reagent volume requirements. Droplet microfluidics have shown exceptional promise for synthetic biology experiments, including DNA assembly, transformation/transfection, culturing, cell sorting, phenotypic assays, artificial cells and genetic circuits.« less

Methods for open innovation on a genome-design platform associating scientific, commercial, and educational communities in synthetic biology.

PubMed

Toyoda, Tetsuro

2011-01-01

Synthetic biology requires both engineering efficiency and compliance with safety guidelines and ethics. Focusing on the rational construction of biological systems based on engineering principles, synthetic biology depends on a genome-design platform to explore the combinations of multiple biological components or BIO bricks for quickly producing innovative devices. This chapter explains the differences among various platform models and details a methodology for promoting open innovation within the scope of the statutory exemption of patent laws. The detailed platform adopts a centralized evaluation model (CEM), computer-aided design (CAD) bricks, and a freemium model. It is also important for the platform to support the legal aspects of copyrights as well as patent and safety guidelines because intellectual work including DNA sequences designed rationally by human intelligence is basically copyrightable. An informational platform with high traceability, transparency, auditability, and security is required for copyright proof, safety compliance, and incentive management for open innovation in synthetic biology. GenoCon, which we have organized and explained here, is a competition-styled, open-innovation method involving worldwide participants from scientific, commercial, and educational communities that aims to improve the designs of genomic sequences that confer a desired function on an organism. Using only a Web browser, a participating contributor proposes a design expressed with CAD bricks that generate a relevant DNA sequence, which is then experimentally and intensively evaluated by the GenoCon organizers. The CAD bricks that comprise programs and databases as a Semantic Web are developed, executed, shared, reused, and well stocked on the secure Semantic Web platform called the Scientists' Networking System or SciNetS/SciNeS, based on which a CEM research center for synthetic biology and open innovation should be established. Copyright © 2011 Elsevier Inc. All rights reserved.

Physcomitrella patens, a versatile synthetic biology chassis.

PubMed

Reski, Ralf; Bae, Hansol; Simonsen, Henrik Toft

2018-05-24

During three decades the moss Physcomitrella patens has been developed to a superb green cell factory with the first commercial products on the market. In the past three decades the moss P. patens has been developed from an obscure bryophyte to a model organism in basic biology, biotechnology, and synthetic biology. Some of the key features of this system include a wide range of Omics technologies, precise genome-engineering via homologous recombination with yeast-like efficiency, a certified good-manufacturing-practice production in bioreactors, successful upscaling to 500 L wave reactors, excellent homogeneity of protein products, superb product stability from batch-to-batch, and a reliable procedure for cryopreservation of cell lines in a master cell bank. About a dozen human proteins are being produced in P. patens as potential biopharmaceuticals, some of them are not only similar to their animal-produced counterparts, but are real biobetters with superior performance. A moss-made pharmaceutical successfully passed phase 1 clinical trials, a fragrant moss, and a cosmetic moss-product is already on the market, highlighting the economic potential of this synthetic biology chassis. Here, we focus on the features of mosses as versatile cell factories for synthetic biology and their impact on metabolic engineering.

Phage Therapy in the Era of Synthetic Biology.

PubMed

Barbu, E Magda; Cady, Kyle C; Hubby, Bolyn

2016-10-03

For more than a century, bacteriophage (or phage) research has enabled some of the most important discoveries in biological sciences and has equipped scientists with many of the molecular biology tools that have advanced our understanding of replication, maintenance, and expression of genetic material. Phages have also been recognized and exploited as natural antimicrobial agents and nanovectors for gene therapy, but their potential as therapeutics has not been fully exploited in Western medicine because of challenges such as narrow host range, bacterial resistance, and unique pharmacokinetics. However, increasing concern related to the emergence of bacteria resistant to multiple antibiotics has heightened interest in phage therapy and the development of strategies to overcome hurdles associated with bacteriophage therapeutics. Recent progress in sequencing technologies, DNA manipulation, and synthetic biology allowed scientists to refactor the entire bacterial genome of Mycoplasma mycoides, thereby creating the first synthetic cell. These new strategies for engineering genomes may have the potential to accelerate the construction of designer phage genomes with superior therapeutic potential. Here, we discuss the use of phage as therapeutics, as well as how synthetic biology can create bacteriophage with desirable attributes. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

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.

Teaching Synthetic Biology, Bioinformatics and Engineering to Undergraduates: The Interdisciplinary Build-a-Genome Course

PubMed Central

Dymond, Jessica S.; Scheifele, Lisa Z.; Richardson, Sarah; Lee, Pablo; Chandrasegaran, Srinivasan; Bader, Joel S.; Boeke, Jef D.

2009-01-01

A major challenge in undergraduate life science curricula is the continual evaluation and development of courses that reflect the constantly shifting face of contemporary biological research. Synthetic biology offers an excellent framework within which students may participate in cutting-edge interdisciplinary research and is therefore an attractive addition to the undergraduate biology curriculum. This new discipline offers the promise of a deeper understanding of gene function, gene order, and chromosome structure through the de novo synthesis of genetic information, much as synthetic approaches informed organic chemistry. While considerable progress has been achieved in the synthesis of entire viral and prokaryotic genomes, fabrication of eukaryotic genomes requires synthesis on a scale that is orders of magnitude higher. These high-throughput but labor-intensive projects serve as an ideal way to introduce undergraduates to hands-on synthetic biology research. We are pursuing synthesis of Saccharomyces cerevisiae chromosomes in an undergraduate laboratory setting, the Build-a-Genome course, thereby exposing students to the engineering of biology on a genomewide scale while focusing on a limited region of the genome. A synthetic chromosome III sequence was designed, ordered from commercial suppliers in the form of oligonucleotides, and subsequently assembled by students into ∼750-bp fragments. Once trained in assembly of such DNA “building blocks” by PCR, the students accomplish high-yield gene synthesis, becoming not only technically proficient but also constructively critical and capable of adapting their protocols as independent researchers. Regular “lab meeting” sessions help prepare them for future roles in laboratory science. PMID:19015540

Biotechnology by Design: An Introductory Level, Project-Based, Synthetic Biology Laboratory Program for Undergraduate Students.

PubMed

Beach, Dale L; Alvarez, Consuelo J

2015-12-01

Synthetic biology offers an ideal opportunity to promote undergraduate laboratory courses with research-style projects, immersing students in an inquiry-based program that enhances the experience of the scientific process. We designed a semester-long, project-based laboratory curriculum using synthetic biology principles to develop a novel sensory device. Students develop subject matter knowledge of molecular genetics and practical skills relevant to molecular biology, recombinant DNA techniques, and information literacy. During the spring semesters of 2014 and 2015, the Synthetic Biology Laboratory Project was delivered to sophomore genetics courses. Using a cloning strategy based on standardized BioBrick genetic "parts," students construct a "reporter plasmid" expressing a reporter gene (GFP) controlled by a hybrid promoter regulated by the lac-repressor protein (lacI). In combination with a "sensor plasmid," the production of the reporter phenotype is inhibited in the presence of a target environmental agent, arabinose. When arabinose is absent, constitutive GFP expression makes cells glow green. But the presence of arabinose activates a second promoter (pBAD) to produce a lac-repressor protein that will inhibit GFP production. Student learning was assessed relative to five learning objectives, using a student survey administered at the beginning (pre-survey) and end (post-survey) of the course, and an additional 15 open-ended questions from five graded Progress Report assignments collected throughout the course. Students demonstrated significant learning gains (p < 0.05) for all learning outcomes. Ninety percent of students indicated that the Synthetic Biology Laboratory Project enhanced their understanding of molecular genetics. The laboratory project is highly adaptable for both introductory and advanced courses.

Teaching synthetic biology, bioinformatics and engineering to undergraduates: the interdisciplinary Build-a-Genome course.

PubMed

Dymond, Jessica S; Scheifele, Lisa Z; Richardson, Sarah; Lee, Pablo; Chandrasegaran, Srinivasan; Bader, Joel S; Boeke, Jef D

2009-01-01

A major challenge in undergraduate life science curricula is the continual evaluation and development of courses that reflect the constantly shifting face of contemporary biological research. Synthetic biology offers an excellent framework within which students may participate in cutting-edge interdisciplinary research and is therefore an attractive addition to the undergraduate biology curriculum. This new discipline offers the promise of a deeper understanding of gene function, gene order, and chromosome structure through the de novo synthesis of genetic information, much as synthetic approaches informed organic chemistry. While considerable progress has been achieved in the synthesis of entire viral and prokaryotic genomes, fabrication of eukaryotic genomes requires synthesis on a scale that is orders of magnitude higher. These high-throughput but labor-intensive projects serve as an ideal way to introduce undergraduates to hands-on synthetic biology research. We are pursuing synthesis of Saccharomyces cerevisiae chromosomes in an undergraduate laboratory setting, the Build-a-Genome course, thereby exposing students to the engineering of biology on a genomewide scale while focusing on a limited region of the genome. A synthetic chromosome III sequence was designed, ordered from commercial suppliers in the form of oligonucleotides, and subsequently assembled by students into approximately 750-bp fragments. Once trained in assembly of such DNA "building blocks" by PCR, the students accomplish high-yield gene synthesis, becoming not only technically proficient but also constructively critical and capable of adapting their protocols as independent researchers. Regular "lab meeting" sessions help prepare them for future roles in laboratory science.

Synthetic biology for microbial production of lipid-based biofuels

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

d’Espaux, Leo; Mendez-Perez, Daniel; Li, Rachel

The risks of maintaining current CO 2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO 2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here in this paper we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. Lastly, we further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential ofmore » synthetic biology for sustainable manufacturing.« less

Consequentialism and the Synthetic Biology Problem.

PubMed

Heavey, Patrick

2017-04-01

This article analyzes the ethics of synthetic biology (synbio) from a consequentialist perspective, examining potential effects on food and agriculture, and on medicine, fuel, and the advancement of science. The issues of biosafety and biosecurity are also examined. A consequentialist analysis offers an essential road map to policymakers and regulators as to how to deal with synbio. Additionally, the article discusses the limitations of consequentialism as a tool for analysing synbioethics. Is it possible to predict, with any degree of plausibility, what the consequences of synthetic biology will be in 50 years, or in 100, or in 500? Synbio may take humanity to a place of radical departure from what is known or knowable.

Synthetic biology: regulating industry uses of new biotechnologies.

PubMed

Erickson, Brent; Singh, Rina; Winters, Paul

2011-09-02

In our view, synthetic biology is an extension of the continuum of genetic science that has been used safely for more than 40 years by the biotechnology industry in the development of commercial products. Examples of synthetic biology use by biotechnology companies illustrate the potential to substantially reduce research and development time and to increase speed to market. Improvements in the speed and cost of DNA synthesis are enabling scientists to design modified bacterial chromosomes that can be used in the production of renewable chemicals, biofuels, bioproducts, renewable specialty chemicals, pharmaceutical intermediates, fine chemicals, food ingredients, and health care products. Regulatory options should support innovation and commercial development of new products while protecting the public from potential harms.

Application of synthetic biology in cyanobacteria and algae

PubMed Central

Wang, Bo; Wang, Jiangxin; Zhang, Weiwen; Meldrum, Deirdre R.

2012-01-01

Cyanobacteria and algae are becoming increasingly attractive cell factories for producing renewable biofuels and chemicals due to their ability to capture solar energy and CO2 and their relatively simple genetic background for genetic manipulation. Increasing research efforts from the synthetic biology approach have been made in recent years to modify cyanobacteria and algae for various biotechnological applications. In this article, we critically review recent progresses in developing genetic tools for characterizing or manipulating cyanobacteria and algae, the applications of genetically modified strains for synthesizing renewable products such as biofuels and chemicals. In addition, the emergent challenges in the development and application of synthetic biology for cyanobacteria and algae are also discussed. PMID:23049529

Synthetic Biology Platform for Sensing and Integrating Endogenous Transcriptional Inputs in Mammalian Cells.

PubMed

Angelici, Bartolomeo; Mailand, Erik; Haefliger, Benjamin; Benenson, Yaakov

2016-08-30

One of the goals of synthetic biology is to develop programmable artificial gene networks that can transduce multiple endogenous molecular cues to precisely control cell behavior. Realizing this vision requires interfacing natural molecular inputs with synthetic components that generate functional molecular outputs. Interfacing synthetic circuits with endogenous mammalian transcription factors has been particularly difficult. Here, we describe a systematic approach that enables integration and transduction of multiple mammalian transcription factor inputs by a synthetic network. The approach is facilitated by a proportional amplifier sensor based on synergistic positive autoregulation. The circuits efficiently transduce endogenous transcription factor levels into RNAi, transcriptional transactivation, and site-specific recombination. They also enable AND logic between pairs of arbitrary transcription factors. The results establish a framework for developing synthetic gene networks that interface with cellular processes through transcriptional regulators. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Novel strategies to construct complex synthetic vectors to produce DNA molecular weight standards.

PubMed

Chen, Zhe; Wu, Jianbing; Li, Xiaojuan; Ye, Chunjiang; Wenxing, He

2009-05-01

DNA molecular weight standards (DNA markers, nucleic acid ladders) are commonly used in molecular biology laboratories as references to estimate the size of various DNA samples in electrophoresis process. One method of DNA marker production is digestion of synthetic vectors harboring multiple DNA fragments of known sizes by restriction enzymes. In this article, we described three novel strategies-sequential DNA fragment ligation, screening of ligation products by polymerase chain reaction (PCR) with end primers, and "small fragment accumulation"-for constructing complex synthetic vectors and minimizing the mass differences between DNA fragments produced from restrictive digestion of synthetic vectors. The strategy could be applied to construct various complex synthetic vectors to produce any type of low-range DNA markers, usually available commercially. In addition, the strategy is useful for single-step ligation of multiple DNA fragments for construction of complex synthetic vectors and other applications in molecular biology field.

How do light harvesting proteins support long lived quantum coherences

DTIC Science & Technology

2017-01-31

the structural basis for these two forms, our aim is to generate hybrid proteins via synthetic biology approaches. We have shown that we can fully...SUBJECT TERMS quantum biology , light harvesting, photosynthesis, AOARD 16.  SECURITY CLASSIFICATION OF: 17.  LIMITATION OF ABSTRACT SAR 18.  NUMBER OF...these two forms, our aim is to generate hybrid proteins via synthetic biology approaches. We have shown that we can fully unfold and separate the

EcoFlex: A Multifunctional MoClo Kit for E. coli Synthetic Biology.

PubMed

Moore, Simon J; Lai, Hung-En; Kelwick, Richard J R; Chee, Soo Mei; Bell, David J; Polizzi, Karen Marie; Freemont, Paul S

2016-10-21

Golden Gate cloning is a prominent DNA assembly tool in synthetic biology for the assembly of plasmid constructs often used in combinatorial pathway optimization, with a number of assembly kits developed specifically for yeast and plant-based expression. However, its use for synthetic biology in commonly used bacterial systems such as Escherichia coli has surprisingly been overlooked. Here, we introduce EcoFlex a simplified modular package of DNA parts for a variety of applications in E. coli, cell-free protein synthesis, protein purification and hierarchical assembly of transcription units based on the MoClo assembly standard. The kit features a library of constitutive promoters, T7 expression, RBS strength variants, synthetic terminators, protein purification tags and fluorescence proteins. We validate EcoFlex by assembling a 68-part containing (20 genes) plasmid (31 kb), characterize in vivo and in vitro library parts, and perform combinatorial pathway assembly, using pooled libraries of either fluorescent proteins or the biosynthetic genes for the antimicrobial pigment violacein as a proof-of-concept. To minimize pathway screening, we also introduce a secondary module design site to simplify MoClo pathway optimization. In summary, EcoFlex provides a standardized and multifunctional kit for a variety of applications in E. coli synthetic biology.

Chemical Engineering in the "BIO" World.

PubMed

Chiarappa, Gianluca; Grassi, Mario; Abrami, Michela; Abbiati, Roberto Andrea; Barba, Anna Angela; Boisen, Anja; Brucato, Valerio; Ghersi, Giulio; Caccavo, Diego; Cascone, Sara; Caserta, Sergio; Elvassore, Nicola; Giomo, Monica; Guido, Stefano; Lamberti, Gaetano; Larobina, Domenico; Manca, Davide; Marizza, Paolo; Tomaiuolo, Giovanna; Grassi, Gabriele

2017-01-01

Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical engineers to transfer laboratory findings to the industrial level. Since then, Chemical Engineering underwent huge transformations determining the detachment from the original Chemistry nest. The beginning of the sixties of the 20th century saw the development of a new branch of Chemical Engineering baptized Biomedical Engineering by Peppas and Langer and that now we can name Biological Engineering. Interestingly, although Biological Engineering focused on completely different topics from Chemical Engineering ones, it resorted to the same theoretical tools such as, for instance, mass, energy and momentum balances. Thus, the birth of Biological Engineering may be considered as a Darwinian evolution of Chemical Engineering similar to that experienced by mammals which, returning to water, used legs and arms to swim. From 1960 on, Biological Engineering underwent a considerable evolution as witnessed by the great variety of topics covered such as hemodialysis, release of synthetic drugs, artificial organs and, more recently, delivery of small interfering RNAs (siRNA). This review, based on the activities developed in the frame of our PRIN 2010-11 (20109PLMH2) project, tries to recount origins and evolution of Chemical Engineering illustrating several examples of recent and successful applications in the biological field. This, in turn, may stimulate the discussion about the Chemical Engineering students curriculum studiorum update. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Technical Challenges in the Development of a NASA Synthetic Vision System Concept

NASA Technical Reports Server (NTRS)

Bailey, Randall E.; Parrish, Russell V.; Kramer, Lynda J.; Harrah, Steve; Arthur, J. J., III

2002-01-01

Within NASA's Aviation Safety Program, the Synthetic Vision Systems Project is developing display system concepts to improve pilot terrain/situation awareness by providing a perspective synthetic view of the outside world through an on-board database driven by precise aircraft positioning information updating via Global Positioning System-based data. This work is aimed at eliminating visibility-induced errors and low visibility conditions as a causal factor to civil aircraft accidents, as well as replicating the operational benefits of clear day flight operations regardless of the actual outside visibility condition. Synthetic vision research and development activities at NASA Langley Research Center are focused around a series of ground simulation and flight test experiments designed to evaluate, investigate, and assess the technology which can lead to operational and certified synthetic vision systems. The technical challenges that have been encountered and that are anticipated in this research and development activity are summarized.

Lipid-Based Nanoparticles as Pharmaceutical Drug Carriers: From Concepts to Clinic

PubMed Central

Puri, Anu; Loomis, Kristin; Smith, Brandon; Lee, Jae-Ho; Yavlovich, Amichai; Heldman, Eli; Blumenthal, Robert

2010-01-01

In recent years, various nanotechnology platforms in the area of medical biology, including both diagnostics and therapy, have gained remarkable attention. Moreover, research and development of engineered multifunctional nanoparticles as pharmaceutical drug carriers have spurred exponential growth in applications to medicine in the last decade. Design principles of these nanoparticles, including nano-emulsions, dendrimers, nano-gold, liposomes, drug-carrier conjugates, antibody-drug complexes, and magnetic nanoparticles, are primarily based on unique assemblies of synthetic, natural, or biological components, including but not limited to synthetic polymers, metal ions, oils, and lipids as their building blocks. However, the potential success of these particles in the clinic relies on consideration of important parameters such as nanoparticle fabrication strategies, their physical properties, drug loading efficiencies, drug release potential, and, most importantly, minimum toxicity of the carrier itself. Among these, lipid-based nanoparticles bear the advantage of being the least toxic for in vivo applications, and significant progress has been made in the area of DNA/RNA and drug delivery using lipid-based nanoassemblies. In this review, we will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in drug delivery. We begin with a review of current activities in the field of liposomes (the so-called honorary nanoparticles), and challenging issues of targeting and triggering will be discussed in detail. We will further describe nanoparticles derived from a novel class of amphipathic lipids called bolaamphiphiles with unique lipid assembly features that have been recently examined as drug/DNA delivery vehicles. Finally, an overview of an emerging novel class of particles (based on lipid components other than phospholipids), solid lipid nanoparticles and nanostructured lipid carriers will be presented. We conclude with a few examples of clinically successful formulations of currently available lipid-based nanoparticles. PMID:20402623

The best of both worlds: reaping the benefits from mammalian and bacterial therapeutic circuits.

PubMed

Bojar, Daniel; Fussenegger, Martin

2016-10-01

Synthetic biology has revolutionized the field of biology in the last two decades. By taking apart natural systems and recombining engineered parts in novel constellations, it has not only unlocked a staggering variety of biological control mechanisms but it has also created a panoply of biomedical achievements, such as innovative diagnostics and therapies. The most common mode of action in the field of synthetic biology is mediated by synthetic gene circuits assembled in a systematic and rational manner. This review covers the most recent therapeutic gene circuits implemented in mammalian and bacterial cells designed for the diagnosis and therapy of an extensive array of diseases. Highlighting new tools for therapeutic gene circuits, we describe a future that holds a plethora of potentialities for the medicine of tomorrow. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparing synthetic biology for the world

PubMed Central

Moe-Behrens, Gerd H. G.; Davis, Rene; Haynes, Karmella A.

2013-01-01

Synthetic Biology promises low-cost, exponentially scalable products and global health solutions in the form of self-replicating organisms, or “living devices.” As these promises are realized, proof-of-concept systems will gradually migrate from tightly regulated laboratory or industrial environments into private spaces as, for instance, probiotic health products, food, and even do-it-yourself bioengineered systems. What additional steps, if any, should be taken before releasing engineered self-replicating organisms into a broader user space? In this review, we explain how studies of genetically modified organisms lay groundwork for the future landscape of biosafety. Early in the design process, biological engineers are anticipating potential hazards and developing innovative tools to mitigate risk. Here, we survey lessons learned, ongoing efforts to engineer intrinsic biocontainment, and how different stakeholders in synthetic biology can act to accomplish best practices for biosafety. PMID:23355834

Synthetic biology R&D risks: Social-institutional contexts matter!

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

Wolfe, Amy K.; Bjornstad, David J.; Shumpert, Barry L.

Social and institutional analyses currently are missing from considerations of synthetic biology R&D-related biosafety, which instead have bioethics, governance, or technical orientations. Social and institutional context shapes standard practice. Here, analyzing context helps identify circumstances that create, amplify, or diminish risk, thereby revealing new opportunities for avoiding or managing those risks.

Synthetic biology R&D risks: Social-institutional contexts matter!

DOE PAGES

Wolfe, Amy K.; Bjornstad, David J.; Shumpert, Barry L.; ...

2016-02-15

Social and institutional analyses currently are missing from considerations of synthetic biology R&D-related biosafety, which instead have bioethics, governance, or technical orientations. Social and institutional context shapes standard practice. Here, analyzing context helps identify circumstances that create, amplify, or diminish risk, thereby revealing new opportunities for avoiding or managing those risks.

Mapping the patent landscape of synthetic biology for fine chemical production pathways.

PubMed

Carbonell, Pablo; Gök, Abdullah; Shapira, Philip; Faulon, Jean-Loup

2016-09-01

A goal of synthetic biology bio-foundries is to innovate through an iterative design/build/test/learn pipeline. In assessing the value of new chemical production routes, the intellectual property (IP) novelty of the pathway is important. Exploratory studies can be carried using knowledge of the patent/IP landscape for synthetic biology and metabolic engineering. In this paper, we perform an assessment of pathways as potential targets for chemical production across the full catalogue of reachable chemicals in the extended metabolic space of chassis organisms, as computed by the retrosynthesis-based algorithm RetroPath. Our database for reactions processed by sequences in heterologous pathways was screened against the PatSeq database, a comprehensive collection of more than 150M sequences present in patent grants and applications. We also examine related patent families using Derwent Innovations. This large-scale computational study provides useful insights into the IP landscape of synthetic biology for fine and specialty chemicals production. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Biologic and synthetic skin substitutes: An overview

PubMed Central

Halim, Ahmad Sukari; Khoo, Teng Lye; Mohd. Yussof, Shah Jumaat

2010-01-01

The current trend of burn wound care has shifted to more holistic approach of improvement in the long-term form and function of the healed burn wounds and quality of life. This has demanded the emergence of various skin substitutes in the management of acute burn injury as well as post burn reconstructions. Skin substitutes have important roles in the treatment of deep dermal and full thickness wounds of various aetiologies. At present, there is no ideal substitute in the market. Skin substitutes can be divided into two main classes, namely, biological and synthetic substitutes. The biological skin substitutes have a more intact extracellular matrix structure, while the synthetic skin substitutes can be synthesised on demand and can be modulated for specific purposes. Each class has its advantages and disadvantages. The biological skin substitutes may allow the construction of a more natural new dermis and allow excellent re-epithelialisation characteristics due to the presence of a basement membrane. Synthetic skin substitutes demonstrate the advantages of increase control over scaffold composition. The ultimate goal is to achieve an ideal skin substitute that provides an effective and scar-free wound healing. PMID:21321652

Synthetic biology and the prospects for responsible innovation.

PubMed

Macnaghten, Phil; Owen, Richard; Jackson, Roland

2016-11-30

In this article we provide a short review of the debate on responsible innovation and its intersection with synthetic biology, focusing on initiatives we have witnessed and been involved with in the UK. First, we describe the ways in which responsibility in science has been reconfigured institutionally, from an internal focus on the provision of objective and reliable knowledge, to a more external view that embraces the ways in which it has an impact on society. Secondly, we introduce a framework for responsible innovation as a (partial) response to this shift, highlighting its constituent dimensions and the capacities and competencies that are needed to put it into practice. Thirdly, we chart the development of social science research on synthetic biology, addressing its evolution from an 'ethical, legal and social implications' (ELSI) frame to a responsible innovation frame. Fourthly, we review findings from UK social science research with the synthetic biology community setting out challenges for productive collaboration. And finally, we conclude with suggestions on the need for changes in institutional governance. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Production of Fatty Acid-Derived Valuable Chemicals in Synthetic Microbes

PubMed Central

Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Leong, Susanna Su Jan; Chang, Matthew Wook

2014-01-01

Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fatty acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes. PMID:25566540

GoldenBraid 2.0: A Comprehensive DNA Assembly Framework for Plant Synthetic Biology1[C][W][OA

PubMed Central

Sarrion-Perdigones, Alejandro; Vazquez-Vilar, Marta; Palací, Jorge; Castelijns, Bas; Forment, Javier; Ziarsolo, Peio; Blanca, José; Granell, Antonio; Orzaez, Diego

2013-01-01

Plant synthetic biology aims to apply engineering principles to plant genetic design. One strategic requirement of plant synthetic biology is the adoption of common standardized technologies that facilitate the construction of increasingly complex multigene structures at the DNA level while enabling the exchange of genetic building blocks among plant bioengineers. Here, we describe GoldenBraid 2.0 (GB2.0), a comprehensive technological framework that aims to foster the exchange of standard DNA parts for plant synthetic biology. GB2.0 relies on the use of type IIS restriction enzymes for DNA assembly and proposes a modular cloning schema with positional notation that resembles the grammar of natural languages. Apart from providing an optimized cloning strategy that generates fully exchangeable genetic elements for multigene engineering, the GB2.0 toolkit offers an ever-growing open collection of DNA parts, including a group of functionally tested, premade genetic modules to build frequently used modules like constitutive and inducible expression cassettes, endogenous gene silencing and protein-protein interaction tools, etc. Use of the GB2.0 framework is facilitated by a number of Web resources that include a publicly available database, tutorials, and a software package that provides in silico simulations and laboratory protocols for GB2.0 part domestication and multigene engineering. In short, GB2.0 provides a framework to exchange both information and physical DNA elements among bioengineers to help implement plant synthetic biology projects. PMID:23669743

GoldenBraid 2.0: a comprehensive DNA assembly framework for plant synthetic biology.

PubMed

Sarrion-Perdigones, Alejandro; Vazquez-Vilar, Marta; Palací, Jorge; Castelijns, Bas; Forment, Javier; Ziarsolo, Peio; Blanca, José; Granell, Antonio; Orzaez, Diego

2013-07-01

Plant synthetic biology aims to apply engineering principles to plant genetic design. One strategic requirement of plant synthetic biology is the adoption of common standardized technologies that facilitate the construction of increasingly complex multigene structures at the DNA level while enabling the exchange of genetic building blocks among plant bioengineers. Here, we describe GoldenBraid 2.0 (GB2.0), a comprehensive technological framework that aims to foster the exchange of standard DNA parts for plant synthetic biology. GB2.0 relies on the use of type IIS restriction enzymes for DNA assembly and proposes a modular cloning schema with positional notation that resembles the grammar of natural languages. Apart from providing an optimized cloning strategy that generates fully exchangeable genetic elements for multigene engineering, the GB2.0 toolkit offers an evergrowing open collection of DNA parts, including a group of functionally tested, premade genetic modules to build frequently used modules like constitutive and inducible expression cassettes, endogenous gene silencing and protein-protein interaction tools, etc. Use of the GB2.0 framework is facilitated by a number of Web resources that include a publicly available database, tutorials, and a software package that provides in silico simulations and laboratory protocols for GB2.0 part domestication and multigene engineering. In short, GB2.0 provides a framework to exchange both information and physical DNA elements among bioengineers to help implement plant synthetic biology projects.

Plant synthetic biology: a new platform for industrial biotechnology.

PubMed

Fesenko, Elena; Edwards, Robert

2014-05-01

Thirty years after the production of the first generation of genetically modified plants we are now set to move into a new era of recombinant crop technology through the application of synthetic biology to engineer new and complex input and output traits. The use of synthetic biology technologies will represent more than incremental additions of transgenes, but rather the directed design of completely new metabolic pathways, physiological traits, and developmental control strategies. The need to enhance our ability to improve crops through new engineering capability is now increasingly pressing as we turn to plants not just for food, but as a source of renewable feedstocks for industry. These accelerating and diversifying demands for new output traits coincide with a need to reduce inputs and improve agricultural sustainability. Faced with such challenges, existing technologies will need to be supplemented with new and far-more-directed approaches to turn valuable resources more efficiently into usable agricultural products. While these objectives are challenging enough, the use of synthetic biology in crop improvement will face public acceptance issues as a legacy of genetically modified technologies in many countries. Here we review some of the potential benefits of adopting synthetic biology approaches in improving plant input and output traits for their use as industrial chemical feedstocks, as linked to the rapidly developing biorefining industry. Several promising technologies and biotechnological targets are identified along with some of the key regulatory and societal challenges in the safe and acceptable introduction of such technology.

Playing God in Frankenstein's Footsteps: Synthetic Biology and the Meaning of Life.

PubMed

van den Belt, Henk

2009-12-01

The emergent new science of synthetic biology is challenging entrenched distinctions between, amongst others, life and non-life, the natural and the artificial, the evolved and the designed, and even the material and the informational. Whenever such culturally sanctioned boundaries are breached, researchers are inevitably accused of playing God or treading in Frankenstein's footsteps. Bioethicists, theologians and editors of scientific journals feel obliged to provide an authoritative answer to the ambiguous question of the 'meaning' of life, both as a scientific definition and as an explication with wider existential connotations. This article analyses the arguments mooted in the emerging societal debates on synthetic biology and the way its practitioners respond to criticism, mostly by assuming a defiant posture or professing humility. It explores the relationship between the 'playing God' theme and the Frankenstein motif and examines the doctrinal status of the 'playing God' argument. One particularly interesting finding is that liberal theologians generally deny the religious character of the 'playing God' argument-a response which fits in with the curious fact that this argument is used mainly by secular organizations. Synthetic biology, it is therefore maintained, does not offend so much the God of the Bible as a deified Nature. While syntheses of artificial life forms cause some vague uneasiness that life may lose its special meaning, most concerns turn out to be narrowly anthropocentric. As long as synthetic biology creates only new microbial life and does not directly affect human life, it will in all likelihood be considered acceptable.

Image of Synthetic Biology and Nanotechnology: A Survey among University Students

PubMed Central

Ineichen, Christian; Biller-Andorno, Nikola; Deplazes-Zemp, Anna

2017-01-01

This study explores the image of synthetic biology and nanotechnology in comparison to agricultural biotechnology and communication technology by examining spontaneous associations with, and deliberate evaluations of, these technologies by university students. Data were collected through a self-completion online questionnaire by students from two universities in Switzerland. The survey aimed to capture implicit associations, explicit harm-benefit evaluations and views on regulation. The data suggest overall positive associations with emerging technologies. While positive associations were most pronounced for nanotechnology, agricultural biotechnology was attributed with the least favorable associations. In contrast to its positive result in the association task, respondents attributed a high harm potential for nanotechnology. Associations attributed to synthetic biology were demonstrated to be more positive than for agricultural biotechnology, however, not as favorable as for nanotechnology. Contrary to the evaluations of nanotechnology, the benefit-examples of synthetic biology were evaluated particularly positively. Accordingly, the investigated technologies enjoy different esteem, with synthetic biology and nanotechnology both showing a more “exciting” image. Even though, the image of nanotechnology was demonstrated to be more pronounced it was also more heterogeneous across tasks while agricultural biotechnology remains contested. For all technologies, the predominant spontaneous concerns pertain to risks rather than an immoral nature inherent to these technologies. Our data suggest that harm-benefit analyses reveal only one aspect of the attitude toward emerging technologies. Survey questions addressing spontaneous associations with these technologies are a valuable addition for our picture of the image of emerging technologies. PMID:28979291

Synthetic biology and its alternatives. Descartes, Kant and the idea of engineering biological machines.

PubMed

Kogge, Werner; Richter, Michael

2013-06-01

The engineering-based approach of synthetic biology is characterized by an assumption that 'engineering by design' enables the construction of 'living machines'. These 'machines', as biological machines, are expected to display certain properties of life, such as adapting to changing environments and acting in a situated way. This paper proposes that a tension exists between the expectations placed on biological artefacts and the notion of producing such systems by means of engineering; this tension makes it seem implausible that biological systems, especially those with properties characteristic of living beings, can in fact be produced using the specific methods of engineering. We do not claim that engineering techniques have nothing to contribute to the biotechnological construction of biological artefacts. However, drawing on Descartes's and Kant's thinking on the relationship between the organism and the machine, we show that it is considerably more plausible to assume that distinctively biological artefacts emerge within a paradigm different from the paradigm of the Cartesian machine that underlies the engineering approach. We close by calling for increased attention to be paid to approaches within molecular biology and chemistry that rest on conceptions different from those of synthetic biology's engineering paradigm. Copyright © 2013 Elsevier Ltd. All rights reserved.

Application of geostatistical simulation to compile seismotectonic provinces based on earthquake databases (case study: Iran)

NASA Astrophysics Data System (ADS)

Jalali, Mohammad; Ramazi, Hamidreza

2018-04-01

This article is devoted to application of a simulation algorithm based on geostatistical methods to compile and update seismotectonic provinces in which Iran has been chosen as a case study. Traditionally, tectonic maps together with seismological data and information (e.g., earthquake catalogues, earthquake mechanism, and microseismic data) have been used to update seismotectonic provinces. In many cases, incomplete earthquake catalogues are one of the important challenges in this procedure. To overcome this problem, a geostatistical simulation algorithm, turning band simulation, TBSIM, was applied to make a synthetic data to improve incomplete earthquake catalogues. Then, the synthetic data was added to the traditional information to study the seismicity homogeneity and classify the areas according to tectonic and seismic properties to update seismotectonic provinces. In this paper, (i) different magnitude types in the studied catalogues have been homogenized to moment magnitude (Mw), and earthquake declustering was then carried out to remove aftershocks and foreshocks; (ii) time normalization method was introduced to decrease the uncertainty in a temporal domain prior to start the simulation procedure; (iii) variography has been carried out in each subregion to study spatial regressions (e.g., west-southwestern area showed a spatial regression from 0.4 to 1.4 decimal degrees; the maximum range identified in the azimuth of 135 ± 10); (iv) TBSIM algorithm was then applied to make simulated events which gave rise to make 68,800 synthetic events according to the spatial regression found in several directions; (v) simulated events (i.e., magnitudes) were classified based on their intensity in ArcGIS packages and homogenous seismic zones have been determined. Finally, according to the synthetic data, tectonic features, and actual earthquake catalogues, 17 seismotectonic provinces were introduced in four major classes introduced as very high, high, moderate, and low seismic potential provinces. Seismotectonic properties of very high seismic potential provinces have been also presented.

The conception of life in synthetic biology.

PubMed

Deplazes-Zemp, Anna

2012-12-01

The phrase 'synthetic biology' is used to describe a set of different scientific and technological disciplines, which share the objective to design and produce new life forms. This essay addresses the following questions: What conception of life stands behind this ambitious objective? In what relation does this conception of life stand to that of traditional biology and biotechnology? And, could such a conception of life raise ethical concerns? Three different observations that provide useful indications for the conception of life in synthetic biology will be discussed in detail: 1. Synthetic biologists focus on different features of living organisms in order to design new life forms, 2. Synthetic biologists want to contribute to the understanding of life, and 3. Synthetic biologists want to modify life through a rational design, which implies the notions of utilising, minimising/optimising, varying and overcoming life. These observations indicate a tight connection between science and technology, a focus on selected aspects of life, a production-oriented approach to life, and a design-oriented understanding of life. It will be argued that through this conception of life synthetic biologists present life in a different light. This conception of life will be illustrated by the metaphor of a toolbox. According to the notion of life as a toolbox, the different features of living organisms are perceived as various rationally designed instruments that can be used for the production of the living organism itself or secondary products made by the organism. According to certain ethical positions this conception of life might raise ethical concerns related to the status of the organism, the motives of the scientists and the role of technology in our society.

Biological Dual-Use Research and Synthetic Biology of Yeast.

PubMed

Cirigliano, Angela; Cenciarelli, Orlando; Malizia, Andrea; Bellecci, Carlo; Gaudio, Pasquale; Lioj, Michele; Rinaldi, Teresa

2017-04-01

In recent years, the publication of the studies on the transmissibility in mammals of the H5N1 influenza virus and synthetic genomes has triggered heated and concerned debate within the community of scientists on biological dual-use research; these papers have raised the awareness that, in some cases, fundamental research could be directed to harmful experiments, with the purpose of developing a weapon that could be used by a bioterrorist. Here is presented an overview regarding the dual-use concept and its related international agreements which underlines the work of the Australia Group (AG) Export Control Regime. It is hoped that the principles and activities of the AG, that focuses on export control of chemical and biological dual-use materials, will spread and become well known to academic researchers in different countries, as they exchange biological materials (i.e. plasmids, strains, antibodies, nucleic acids) and scientific papers. To this extent, and with the aim of drawing the attention of the scientific community that works with yeast to the so called Dual-Use Research of Concern, this article reports case studies on biological dual-use research and discusses a synthetic biology applied to the yeast Saccharomyces cerevisiae, namely the construction of the first eukaryotic synthetic chromosome of yeast and the use of yeast cells as a factory to produce opiates. Since this organism is considered harmless and is not included in any list of biological agents, yeast researchers should take simple actions in the future to avoid the sharing of strains and advanced technology with suspicious individuals.

Synthetic biology for CO2 fixation.

PubMed

Gong, Fuyu; Cai, Zhen; Li, Yin

2016-11-01

Recycling of carbon dioxide (CO 2 ) into fuels and chemicals is a potential approach to reduce CO 2 emission and fossil-fuel consumption. Autotrophic microbes can utilize energy from light, hydrogen, or sulfur to assimilate atmospheric CO 2 into organic compounds at ambient temperature and pressure. This provides a feasible way for biological production of fuels and chemicals from CO 2 under normal conditions. Recently great progress has been made in this research area, and dozens of CO 2 -derived fuels and chemicals have been reported to be synthesized by autotrophic microbes. This is accompanied by investigations into natural CO 2 -fixation pathways and the rapid development of new technologies in synthetic biology. This review first summarizes the six natural CO 2 -fixation pathways reported to date, followed by an overview of recent progress in the design and engineering of CO 2 -fixation pathways as well as energy supply patterns using the concept and tools of synthetic biology. Finally, we will discuss future prospects in biological fixation of CO 2 .

Synthetic biology approaches in drug discovery and pharmaceutical biotechnology.

PubMed

Neumann, Heinz; Neumann-Staubitz, Petra

2010-06-01

Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology.

SMART-DS: Synthetic Models for Advanced, Realistic Testing: Distribution Systems and Scenarios

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

Palmintier, Bryan: Hodge, Bri-Mathias

This presentation provides a Smart-DS project overview and status update for the ARPA-e GRID DATA program meeting 2017, including distribution systems, models, and scenarios, as well as opportunities for GRID DATA collaborations.

Synthetic biology as it relates to CAM photosynthesis: challenges and opportunities.

PubMed

DePaoli, Henrique C; Borland, Anne M; Tuskan, Gerald A; Cushman, John C; Yang, Xiaohan

2014-07-01

To meet future food and energy security needs, which are amplified by increasing population growth and reduced natural resource availability, metabolic engineering efforts have moved from manipulating single genes/proteins to introducing multiple genes and novel pathways to improve photosynthetic efficiency in a more comprehensive manner. Biochemical carbon-concentrating mechanisms such as crassulacean acid metabolism (CAM), which improves photosynthetic, water-use, and possibly nutrient-use efficiency, represent a strategic target for synthetic biology to engineer more productive C3 crops for a warmer and drier world. One key challenge for introducing multigene traits like CAM onto a background of C3 photosynthesis is to gain a better understanding of the dynamic spatial and temporal regulatory events that underpin photosynthetic metabolism. With the aid of systems and computational biology, vast amounts of experimental data encompassing transcriptomics, proteomics, and metabolomics can be related in a network to create dynamic models. Such models can undergo simulations to discover key regulatory elements in metabolism and suggest strategic substitution or augmentation by synthetic components to improve photosynthetic performance and water-use efficiency in C3 crops. Another key challenge in the application of synthetic biology to photosynthesis research is to develop efficient systems for multigene assembly and stacking. Here, we review recent progress in computational modelling as applied to plant photosynthesis, with attention to the requirements for CAM, and recent advances in synthetic biology tool development. Lastly, we discuss possible options for multigene pathway construction in plants with an emphasis on CAM-into-C3 engineering. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Biotechnology by Design: An Introductory Level, Project-Based, Synthetic Biology Laboratory Program for Undergraduate Students†

PubMed Central

Beach, Dale L.; Alvarez, Consuelo J.

2015-01-01

Synthetic biology offers an ideal opportunity to promote undergraduate laboratory courses with research-style projects, immersing students in an inquiry-based program that enhances the experience of the scientific process. We designed a semester-long, project-based laboratory curriculum using synthetic biology principles to develop a novel sensory device. Students develop subject matter knowledge of molecular genetics and practical skills relevant to molecular biology, recombinant DNA techniques, and information literacy. During the spring semesters of 2014 and 2015, the Synthetic Biology Laboratory Project was delivered to sophomore genetics courses. Using a cloning strategy based on standardized BioBrick genetic “parts,” students construct a “reporter plasmid” expressing a reporter gene (GFP) controlled by a hybrid promoter regulated by the lac-repressor protein (lacI). In combination with a “sensor plasmid,” the production of the reporter phenotype is inhibited in the presence of a target environmental agent, arabinose. When arabinose is absent, constitutive GFP expression makes cells glow green. But the presence of arabinose activates a second promoter (pBAD) to produce a lac-repressor protein that will inhibit GFP production. Student learning was assessed relative to five learning objectives, using a student survey administered at the beginning (pre-survey) and end (post-survey) of the course, and an additional 15 open-ended questions from five graded Progress Report assignments collected throughout the course. Students demonstrated significant learning gains (p < 0.05) for all learning outcomes. Ninety percent of students indicated that the Synthetic Biology Laboratory Project enhanced their understanding of molecular genetics. The laboratory project is highly adaptable for both introductory and advanced courses. PMID:26753032

Synthetic biology advances for pharmaceutical production

PubMed Central

Breitling, Rainer; Takano, Eriko

2015-01-01

Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems. PMID:25744872

A robust gene-stacking method utilizing yeast assembly for plant synthetic biology

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

Shih, Patrick M.; Vuu, Khanh; Mansoori, Nasim

The advent and growth of synthetic biology has demonstrated its potential as a promising avenue of research to address many societal needs. But, plant synthetic biology efforts have been hampered by a dearth of DNA part libraries, versatile transformation vectors and efficient assembly strategies. We describe a versatile system (named jStack) utilizing yeast homologous recombination to efficiently assemble DNA into plant transformation vectors. We also demonstrate how this method can facilitate pathway engineering of molecules of pharmaceutical interest, production of potential biofuels and shuffling of disease-resistance traits between crop species. Our approach provides a powerful alternative to conventional strategies formore » stacking genes and traits to address many impending environmental and agricultural challenges.« less

[Recent advances of synthetic biology for production of functional ingredients in Chinese materia medica].

PubMed

Su, Xin-Yao; Xue, Jian-Ping; Wang, Cai-Xia

2016-11-01

The functional ingredients in Chinese materia medica are the main active substance for traditional Chinese medicine and most of them are secondary metabolites derivatives. Until now,the main method to obtain those functional ingredients is through direct extraction from the Chinese materia medica. However, the income is very low because of the high extraction costs and the decreased medicinal plants. Synthetic biology technology, as a new and microbial approach, can be able to carry out large-scale production of functional ingredients and greatly ease the shortage of traditional Chinese medicine ingredients. This review mainly focused on the recent advances in synthetic biology for the functional ingredients production. Copyright© by the Chinese Pharmaceutical Association.

A robust gene-stacking method utilizing yeast assembly for plant synthetic biology

DOE PAGES

Shih, Patrick M.; Vuu, Khanh; Mansoori, Nasim; ...

2016-10-26

The advent and growth of synthetic biology has demonstrated its potential as a promising avenue of research to address many societal needs. But, plant synthetic biology efforts have been hampered by a dearth of DNA part libraries, versatile transformation vectors and efficient assembly strategies. We describe a versatile system (named jStack) utilizing yeast homologous recombination to efficiently assemble DNA into plant transformation vectors. We also demonstrate how this method can facilitate pathway engineering of molecules of pharmaceutical interest, production of potential biofuels and shuffling of disease-resistance traits between crop species. Our approach provides a powerful alternative to conventional strategies formore » stacking genes and traits to address many impending environmental and agricultural challenges.« less

Ensuring the security of synthetic biology-towards a 5P governance strategy.

PubMed

Kelle, Alexander

2009-12-01

Over recent years the label "synthetic biology" has been attached to a number of diverse research and commercial activities, ranging from the search for a minimal cell to the quick delivery of customized genes by DNA synthesis companies. Based on the analysis of biosecurity issues surrounding synthetic biology during the SYNBIOSAFE project, this paper will first provide a rationale for taking security, in addition to safety aspects of this new field, seriously. It will then take stock of the initiatives and measures that have already been taken in this area and will lastly try to map out future areas of activities in order to minimise the security risks emanating from this promising new field of scientific inquiry and technological progress.

Systems and synthetic biology approaches to alter plant cell walls and reduce biomass recalcitrance

DOE PAGES

Kalluri, Udaya C.; Yin, Hengfu; Yang, Xiaohan; ...

2014-11-03

Fine-tuning plant cell wall properties to render plant biomass more amenable to biofuel conversion is a colossal challenge. A deep knowledge of the biosynthesis and regulation of plant cell wall and a high-precision genome engineering toolset are the two essential pillars of efforts to alter plant cell walls and reduce biomass recalcitrance. The past decade has seen a meteoric rise in use of transcriptomics and high-resolution imaging methods resulting in fresh insights into composition, structure, formation and deconstruction of plant cell walls. Subsequent gene manipulation approaches, however, commonly include ubiquitous mis-expression of a single candidate gene in a host thatmore » carries an intact copy of the native gene. The challenges posed by pleiotropic and unintended changes resulting from such an approach are moving the field towards synthetic biology approaches. Finally, synthetic biology builds on a systems biology knowledge base and leverages high-precision tools for high-throughput assembly of multigene constructs and pathways, precision genome editing and site-specific gene stacking, silencing and/or removal. Here, we summarize the recent breakthroughs in biosynthesis and remodelling of major secondary cell wall components, assess the impediments in obtaining a systems-level understanding and explore the potential opportunities in leveraging synthetic biology approaches to reduce biomass recalcitrance.« less

Systems and synthetic biology approaches to alter plant cell walls and reduce biomass recalcitrance

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

Kalluri, Udaya C.; Yin, Hengfu; Yang, Xiaohan

Fine-tuning plant cell wall properties to render plant biomass more amenable to biofuel conversion is a colossal challenge. A deep knowledge of the biosynthesis and regulation of plant cell wall and a high-precision genome engineering toolset are the two essential pillars of efforts to alter plant cell walls and reduce biomass recalcitrance. The past decade has seen a meteoric rise in use of transcriptomics and high-resolution imaging methods resulting in fresh insights into composition, structure, formation and deconstruction of plant cell walls. Subsequent gene manipulation approaches, however, commonly include ubiquitous mis-expression of a single candidate gene in a host thatmore » carries an intact copy of the native gene. The challenges posed by pleiotropic and unintended changes resulting from such an approach are moving the field towards synthetic biology approaches. Finally, synthetic biology builds on a systems biology knowledge base and leverages high-precision tools for high-throughput assembly of multigene constructs and pathways, precision genome editing and site-specific gene stacking, silencing and/or removal. Here, we summarize the recent breakthroughs in biosynthesis and remodelling of major secondary cell wall components, assess the impediments in obtaining a systems-level understanding and explore the potential opportunities in leveraging synthetic biology approaches to reduce biomass recalcitrance.« less

Synthetic biology: Novel approaches for microbiology.

PubMed

Padilla-Vaca, Felipe; Anaya-Velázquez, Fernando; Franco, Bernardo

2015-06-01

In the past twenty years, molecular genetics has created powerful tools for genetic manipulation of living organisms. Whole genome sequencing has provided necessary information to assess knowledge on gene function and protein networks. In addition, new tools permit to modify organisms to perform desired tasks. Gene function analysis is speed up by novel approaches that couple both high throughput data generation and mining. Synthetic biology is an emerging field that uses tools for generating novel gene networks, whole genome synthesis and engineering. New applications in biotechnological, pharmaceutical and biomedical research are envisioned for synthetic biology. In recent years these new strategies have opened up the possibilities to study gene and genome editing, creation of novel tools for functional studies in virus, parasites and pathogenic bacteria. There is also the possibility to re-design organisms to generate vaccine subunits or produce new pharmaceuticals to combat multi-drug resistant pathogens. In this review we provide our opinion on the applicability of synthetic biology strategies for functional studies of pathogenic organisms and some applications such as genome editing and gene network studies to further comprehend virulence factors and determinants in pathogenic organisms. We also discuss what we consider important ethical issues for this field of molecular biology, especially for potential misuse of the new technologies. Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.

Eugene--a domain specific language for specifying and constraining synthetic biological parts, devices, and systems.

PubMed

Bilitchenko, Lesia; Liu, Adam; Cheung, Sherine; Weeding, Emma; Xia, Bing; Leguia, Mariana; Anderson, J Christopher; Densmore, Douglas

2011-04-29

Synthetic biological systems are currently created by an ad-hoc, iterative process of specification, design, and assembly. These systems would greatly benefit from a more formalized and rigorous specification of the desired system components as well as constraints on their composition. Therefore, the creation of robust and efficient design flows and tools is imperative. We present a human readable language (Eugene) that allows for the specification of synthetic biological designs based on biological parts, as well as provides a very expressive constraint system to drive the automatic creation of composite Parts (Devices) from a collection of individual Parts. We illustrate Eugene's capabilities in three different areas: Device specification, design space exploration, and assembly and simulation integration. These results highlight Eugene's ability to create combinatorial design spaces and prune these spaces for simulation or physical assembly. Eugene creates functional designs quickly and cost-effectively. Eugene is intended for forward engineering of DNA-based devices, and through its data types and execution semantics, reflects the desired abstraction hierarchy in synthetic biology. Eugene provides a powerful constraint system which can be used to drive the creation of new devices at runtime. It accomplishes all of this while being part of a larger tool chain which includes support for design, simulation, and physical device assembly.

Precision control of recombinant gene transcription for CHO cell synthetic biology.

PubMed

Brown, Adam J; James, David C

2016-01-01

The next generation of mammalian cell factories for biopharmaceutical production will be genetically engineered to possess both generic and product-specific manufacturing capabilities that may not exist naturally. Introduction of entirely new combinations of synthetic functions (e.g. novel metabolic or stress-response pathways), and retro-engineering of existing functional cell modules will drive disruptive change in cellular manufacturing performance. However, before we can apply the core concepts underpinning synthetic biology (design, build, test) to CHO cell engineering we must first develop practical and robust enabling technologies. Fundamentally, we will require the ability to precisely control the relative stoichiometry of numerous functional components we simultaneously introduce into the host cell factory. In this review we discuss how this can be achieved by design of engineered promoters that enable concerted control of recombinant gene transcription. We describe the specific mechanisms of transcriptional regulation that affect promoter function during bioproduction processes, and detail the highly-specific promoter design criteria that are required in the context of CHO cell engineering. The relative applicability of diverse promoter development strategies are discussed, including re-engineering of natural sequences, design of synthetic transcription factor-based systems, and construction of synthetic promoters. This review highlights the potential of promoter engineering to achieve precision transcriptional control for CHO cell synthetic biology. Copyright © 2015. Published by Elsevier Inc.

Rule-Based Design of Plant Expression Vectors Using GenoCAD.

PubMed

Coll, Anna; Wilson, Mandy L; Gruden, Kristina; Peccoud, Jean

2015-01-01

Plant synthetic biology requires software tools to assist on the design of complex multi-genic expression plasmids. Here a vector design strategy to express genes in plants is formalized and implemented as a grammar in GenoCAD, a Computer-Aided Design software for synthetic biology. It includes a library of plant biological parts organized in structural categories and a set of rules describing how to assemble these parts into large constructs. Rules developed here are organized and divided into three main subsections according to the aim of the final construct: protein localization studies, promoter analysis and protein-protein interaction experiments. The GenoCAD plant grammar guides the user through the design while allowing users to customize vectors according to their needs. Therefore the plant grammar implemented in GenoCAD will help plant biologists take advantage of methods from synthetic biology to design expression vectors supporting their research projects.

Synthetic Biology and Human Health: Potential Applications for Spaceflight

NASA Technical Reports Server (NTRS)

Karouia, Fathi; Carr, Christopher; Cai, Yizhi; Chen, Y.; Grenon, Marlene; Larios-Sanz, Maia; Jones, Jeffrey A.; Santos, Orlando

2011-01-01

Human space travelers experience a unique environment that affects homeostasis and physiologic adaptation. Spaceflight-related changes have been reported in the musculo-skeletal, cardiovascular, neurovestibular, endocrine, and immune systems. The spacecraft environment further subjects the traveler to noise and gravitational forces, as well as airborne chemical, microbiological contaminants, and radiation exposure. As humans prepare for longer duration missions effective countermeasures must be developed, verified, and implemented to ensure mission success. Over the past ten years, synthetic biology has opened new avenues for research and development in areas such as biological control, biomaterials, sustainable energy production, bioremediation, and biomedical therapies. The latter in particular is of great interest to the implementation of long-duration human spaceflight capabilities. This article discusses the effects of spaceflight on humans, and reviews current capabilities and potential needs associated with the health of the astronauts where synthetic biology could play an important role in the pursuit of space exploration.

Understanding Biological Regulation Through Synthetic Biology.

PubMed

Bashor, Caleb J; Collins, James J

2018-05-20

Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function. Here, we outline research that uses the process of gene circuit engineering to advance biological discovery. Synthetic gene circuit engineering research has not only refined our understanding of cellular regulation but furnished biologists with a toolkit that can be directed at natural systems to exact precision manipulation of network structure. As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges from systems-level network function.

Plant synthetic biology for molecular engineering of signalling and development.

PubMed

Nemhauser, Jennifer L; Torii, Keiko U

2016-03-02

Molecular genetic studies of model plants in the past few decades have identified many key genes and pathways controlling development, metabolism and environmental responses. Recent technological and informatics advances have led to unprecedented volumes of data that may uncover underlying principles of plants as biological systems. The newly emerged discipline of synthetic biology and related molecular engineering approaches is built on this strong foundation. Today, plant regulatory pathways can be reconstituted in heterologous organisms to identify and manipulate parameters influencing signalling outputs. Moreover, regulatory circuits that include receptors, ligands, signal transduction components, epigenetic machinery and molecular motors can be engineered and introduced into plants to create novel traits in a predictive manner. Here, we provide a brief history of plant synthetic biology and significant recent examples of this approach, focusing on how knowledge generated by the reference plant Arabidopsis thaliana has contributed to the rapid rise of this new discipline, and discuss potential future directions.

Development of the updated system of city underground pipelines based on Visual Studio

NASA Astrophysics Data System (ADS)

Zhang, Jianxiong; Zhu, Yun; Li, Xiangdong

2009-10-01

Our city has owned the integrated pipeline network management system with ArcGIS Engine 9.1 as the bottom development platform and with Oracle9i as basic database for storaging data. In this system, ArcGIS SDE9.1 is applied as the spatial data engine, and the system was a synthetic management software developed with Visual Studio visualization procedures development tools. As the pipeline update function of the system has the phenomenon of slower update and even sometimes the data lost, to ensure the underground pipeline data can real-time be updated conveniently and frequently, and the actuality and integrity of the underground pipeline data, we have increased a new update module in the system developed and researched by ourselves. The module has the powerful data update function, and can realize the function of inputting and outputting and rapid update volume of data. The new developed module adopts Visual Studio visualization procedures development tools, and uses access as the basic database to storage data. We can edit the graphics in AutoCAD software, and realize the database update using link between the graphics and the system. Practice shows that the update module has good compatibility with the original system, reliable and high update efficient of the database.

The Next Generation of Synthetic Biology Chassis: Moving Synthetic Biology from the Laboratory to the Field.

PubMed

Adams, Bryn L

2016-12-16

Escherichia coli (E. coli) has played a pivotal role in the development of genetics and molecular biology as scientific fields. It is therefore not surprising that synthetic biology (SB) was built upon E. coli and continues to dominate the field. However, scientific capabilities have advanced from simple gene mutations to the insertion of rationally designed, complex synthetic circuits and creation of entirely synthetic genomes. The point is rapidly approaching where E. coli is no longer an adequate host for the increasingly sophisticated genetic designs of SB. It is time to develop the next generation of SB chassis; robust organisms that can provide the advanced physiology novel synthetic circuits will require to move SB from the laboratory into fieldable technologies. This can be accomplished by developing chassis-specific genetic toolkits that are as extensive as those for E. coli. However, the holy grail of SB would be the development of a universal toolkit that can be ported into any chassis. This viewpoint article underscores the need for new bacterial chassis, as well as discusses some of the important considerations in their selection. It also highlights a few examples of robust, tractable bacterial species that can meet the demands of tomorrow's state-of-the-art in SB. Significant advances have been made in the first 15 years since this field has emerged. However, the advances over the next 15 years will occur not in laboratory organisms, but in fieldable species where the potential of SB can be fully realized in game changing technology.

Global foot-and-mouth disease research update and gap analysis: 7 - pathogenesis and molecular biology

USDA-ARS?s Scientific Manuscript database

In 2014, the GFRA (Global Foot-and-mouth disease Research Alliance) conducted a gap analysis of FMD (Foot-and-Mouth Disease) research. This work has been updated and reported in a series of papers, in this article we report findings in the fields of 1) pathogenesis and 2) molecular biology. The arti...

Synthetic biology: a challenge to mechanical explanations in biology?

PubMed

Morange, Michel

2012-01-01

In their plans to modify organisms, synthetic biologists have contrasted engineering and tinkering. By drawing this contrast between their endeavors and what has happened during the evolution of organisms by natural selection, they underline the novelty of their projects and justify their ambitions. Synthetic biologists are at odds with a long tradition that has considered organisms as "perfect machines." This tradition had already been questioned by Stephen Jay Gould in the 1970s and received a major blow with the comparison made by François Jacob between organisms and the results of "bricolage" (tinkering). These contrasts between engineering and tinkering, synthetic biology and evolution, have no raison d'être. Machines built by humans are increasingly inspired by observations made on organisms. This is not a simple reversal of the previous trend-the mechanical conception of organisms-in which the characteristics of the latter were explained by comparison with human-built machines. Relations between organisms and machines have always been complex and ambiguous.

Erasing Borders: A Brief Chronicle of Early Synthetic Biology.

PubMed

Peretó, Juli

2016-12-01

Synthetic Biology is currently presented as an emergent field involving the application of engineering principles to living matter. However, the scientific pursuit of making life in a laboratory is not new and has been the ultimate, if somewhat distant, aim of the origin-of-life research program for many years. Actually, over a century ago, the idea that the synthesis of life was indispensable to fully understand its nature already appealed to material scientists and evolutionists alike. Jacques Loeb proposed a research program from an engineering standpoint, following a synthetic method (experimental abiogenesis) and based on his mechanist vision of living beings, which he considered true chemical machines. Early synthetic biology endeavors, such as the premature experiments by Alfonso L. Herrera in Mexico, Stéphane Leduc in France, and John B. Burke in United Kingdom, were easily ridiculed on both scientific and ideological grounds. However, in retrospect, all those attempts should be considered as legitimate and sincere anti-vitalistic efforts to cross the apparent border between inert and living matter.

Synthetic Gene Expression Circuits for Designing Precision Tools in Oncology

PubMed Central

Re, Angela

2017-01-01

Precision medicine in oncology needs to enhance its capabilities to match diagnostic and therapeutic technologies to individual patients. Synthetic biology streamlines the design and construction of functionalized devices through standardization and rational engineering of basic biological elements decoupled from their natural context. Remarkable improvements have opened the prospects for the availability of synthetic devices of enhanced mechanism clarity, robustness, sensitivity, as well as scalability and portability, which might bring new capabilities in precision cancer medicine implementations. In this review, we begin by presenting a brief overview of some of the major advances in the engineering of synthetic genetic circuits aimed to the control of gene expression and operating at the transcriptional, post-transcriptional/translational, and post-translational levels. We then focus on engineering synthetic circuits as an enabling methodology for the successful establishment of precision technologies in oncology. We describe significant advancements in our capabilities to tailor synthetic genetic circuits to specific applications in tumor diagnosis, tumor cell- and gene-based therapy, and drug delivery. PMID:28894736

Synthetic Biology R&D Risks: Social-Institutional Contexts Matter!

PubMed

Wolfe, Amy K; Campa, Maria Fernanda; Bergmann, Rachael A; Stelling, Savannah C; Bjornstad, David J; Shumpert, Barry L

2016-05-01

Factors that shape actual research practices - 'social and institutional context' - typically are missing from considerations of synthetic biology R&D-related risk and containment. We argue that analyzing context is essential in identifying circumstances that create, amplify, or diminish risk, and in revealing new opportunities for avoiding or managing those risks. Copyright © 2016 Elsevier Ltd. All rights reserved.

Design and construction of a first-generation high-throughput integrated molecular biology platform for production of optimized synthetic genes and improved industrial strains

USDA-ARS?s Scientific Manuscript database

The molecular biological techniques for plasmid-based assembly and cloning of synthetic assembled gene open reading frames are essential for elucidating the function of the proteins encoded by the genes. These techniques involve the production of full-length cDNA libraries as a source of plasmid-bas...

The bacterial nanorecorder: engineering E. coli to function as a chemical recording device.

PubMed

Bhomkar, Prasanna; Materi, Wayne; Wishart, David S

2011-01-01

Synthetic biology is an emerging branch of molecular biology that uses synthetic genetic constructs to create man-made cells or organisms that are capable of performing novel and/or useful applications. Using a synthetic chemically sensitive genetic toggle switch to activate appropriate fluorescent protein indicators (GFP, RFP) and a cell division inhibitor (minC), we have created a novel E. coli strain that can be used as a highly specific, yet simple and inexpensive chemical recording device. This biological "nanorecorder" can be used to determine both the type and the time at which a brief chemical exposure event has occurred. In particular, we show that the short-term exposure (15-30 min) of cells harboring this synthetic genetic circuit to small molecule signals (anhydrotetracycline or IPTG) triggered long-term and uniform cell elongation, with cell length being directly proportional to the time elapsed following a brief chemical exposure. This work demonstrates that facile modification of an existing genetic toggle switch can be exploited to generate a robust, biologically-based "nanorecorder" that could potentially be adapted to detect, respond and record a wide range of chemical stimuli that may vary over time and space.

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.

How to Make a Synthetic Multicellular Computer

PubMed Central

Macia, Javier; Sole, Ricard

2014-01-01

Biological systems perform computations at multiple scales and they do so in a robust way. Engineering metaphors have often been used in order to provide a rationale for modeling cellular and molecular computing networks and as the basis for their synthetic design. However, a major constraint in this mapping between electronic and wet computational circuits is the wiring problem. Although wires are identical within electronic devices, they must be different when using synthetic biology designs. Moreover, in most cases the designed molecular systems cannot be reused for other functions. A new approximation allows us to simplify the problem by using synthetic cellular consortia where the output of the computation is distributed over multiple engineered cells. By evolving circuits in silico, we can obtain the minimal sets of Boolean units required to solve the given problem at the lowest cost using cellular consortia. Our analysis reveals that the basic set of logic units is typically non-standard. Among the most common units, the so called inverted IMPLIES (N-Implies) appears to be one of the most important elements along with the NOT and AND functions. Although NOR and NAND gates are widely used in electronics, evolved circuits based on combinations of these gates are rare, thus suggesting that the strategy of combining the same basic logic gates might be inappropriate in order to easily implement synthetic computational constructs. The implications for future synthetic designs, the general view of synthetic biology as a standard engineering domain, as well as potencial drawbacks are outlined. PMID:24586222

A synthetic biology approach to the development of transcriptional regulatory models and custom enhancer design☆,☆☆

PubMed Central

Martinez, Carlos A.; Barr, Kenneth; Kim, Ah-Ram; Reinitz, John

2013-01-01

Synthetic biology offers novel opportunities for elucidating transcriptional regulatory mechanisms and enhancer logic. Complex cis-regulatory sequences—like the ones driving expression of the Drosophila even-skipped gene—have proven difficult to design from existing knowledge, presumably due to the large number of protein-protein interactions needed to drive the correct expression patterns of genes in multicellular organisms. This work discusses two novel computational methods for the custom design of enhancers that employ a sophisticated, empirically validated transcriptional model, optimization algorithms, and synthetic biology. These synthetic elements have both utilitarian and academic value, including improving existing regulatory models as well as evolutionary questions. The first method involves the use of simulated annealing to explore the sequence space for synthetic enhancers whose expression output fit a given search criterion. The second method uses a novel optimization algorithm to find functionally accessible pathways between two enhancer sequences. These paths describe a set of mutations wherein the predicted expression pattern does not significantly vary at any point along the path. Both methods rely on a predictive mathematical framework that maps the enhancer sequence space to functional output. PMID:23732772

Synthetic analog computation in living cells.

PubMed

Daniel, Ramiz; Rubens, Jacob R; Sarpeshkar, Rahul; Lu, Timothy K

2013-05-30

A central goal of synthetic biology is to achieve multi-signal integration and processing in living cells for diagnostic, therapeutic and biotechnology applications. Digital logic has been used to build small-scale circuits, but other frameworks may be needed for efficient computation in the resource-limited environments of cells. Here we demonstrate that synthetic analog gene circuits can be engineered to execute sophisticated computational functions in living cells using just three transcription factors. Such synthetic analog gene circuits exploit feedback to implement logarithmically linear sensing, addition, ratiometric and power-law computations. The circuits exhibit Weber's law behaviour as in natural biological systems, operate over a wide dynamic range of up to four orders of magnitude and can be designed to have tunable transfer functions. Our circuits can be composed to implement higher-order functions that are well described by both intricate biochemical models and simple mathematical functions. By exploiting analog building-block functions that are already naturally present in cells, this approach efficiently implements arithmetic operations and complex functions in the logarithmic domain. Such circuits may lead to new applications for synthetic biology and biotechnology that require complex computations with limited parts, need wide-dynamic-range biosensing or would benefit from the fine control of gene expression.

A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions

PubMed Central

Khalil, Ahmad S.; Lu, Timothy K.; Bashor, Caleb J.; Ramirez, Cherie L.; Pyenson, Nora C.; Joung, J. Keith; Collins, James J.

2013-01-01

SUMMARY Eukaryotic transcription factors (TFs) perform complex and combinatorial functions within transcriptional networks. Here, we present a synthetic framework for systematically constructing eukaryotic transcription functions using artificial zinc fingers, modular DNA-binding domains found within many eukaryotic TFs. Utilizing this platform, we construct a library of orthogonal synthetic transcription factors (sTFs) and use these to wire synthetic transcriptional circuits in yeast. We engineer complex functions, such as tunable output strength and transcriptional cooperativity, by rationally adjusting a decomposed set of key component properties, e.g., DNA specificity, affinity, promoter design, protein-protein interactions. We show that subtle perturbations to these properties can transform an individual sTF between distinct roles (activator, cooperative factor, inhibitory factor) within a transcriptional complex, thus drastically altering the signal processing behavior of multi-input systems. This platform provides new genetic components for synthetic biology and enables bottom-up approaches to understanding the design principles of eukaryotic transcriptional complexes and networks. PMID:22863014

Systems and synthetic biology approaches to alter plant cell walls and reduce biomass recalcitrance.

PubMed

Kalluri, Udaya C; Yin, Hengfu; Yang, Xiaohan; Davison, Brian H

2014-12-01

Fine-tuning plant cell wall properties to render plant biomass more amenable to biofuel conversion is a colossal challenge. A deep knowledge of the biosynthesis and regulation of plant cell wall and a high-precision genome engineering toolset are the two essential pillars of efforts to alter plant cell walls and reduce biomass recalcitrance. The past decade has seen a meteoric rise in use of transcriptomics and high-resolution imaging methods resulting in fresh insights into composition, structure, formation and deconstruction of plant cell walls. Subsequent gene manipulation approaches, however, commonly include ubiquitous mis-expression of a single candidate gene in a host that carries an intact copy of the native gene. The challenges posed by pleiotropic and unintended changes resulting from such an approach are moving the field towards synthetic biology approaches. Synthetic biology builds on a systems biology knowledge base and leverages high-precision tools for high-throughput assembly of multigene constructs and pathways, precision genome editing and site-specific gene stacking, silencing and/or removal. Here, we summarize the recent breakthroughs in biosynthesis and remodelling of major secondary cell wall components, assess the impediments in obtaining a systems-level understanding and explore the potential opportunities in leveraging synthetic biology approaches to reduce biomass recalcitrance. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Microbial production of natural and non-natural flavonoids: Pathway engineering, directed evolution and systems/synthetic biology.

PubMed

Pandey, Ramesh Prasad; Parajuli, Prakash; Koffas, Mattheos A G; Sohng, Jae Kyung

2016-01-01

In this review, we address recent advances made in pathway engineering, directed evolution, and systems/synthetic biology approaches employed in the production and modification of flavonoids from microbial cells. The review is divided into two major parts. In the first, various metabolic engineering and system/synthetic biology approaches used for production of flavonoids and derivatives are discussed broadly. All the manipulations/engineering accomplished on the microorganisms since 2000 are described in detail along with the biosynthetic pathway enzymes, their sources, structures of the compounds, and yield of each product. In the second part of the review, post-modifications of flavonoids by four major reactions, namely glycosylations, methylations, hydroxylations and prenylations using recombinant strains are described. Copyright © 2016 Elsevier Inc. All rights reserved.

The metaphysical lessons of synthetic biology and neuroscience.

PubMed

Baertschi, Bernard

2015-01-01

In this paper, I examine some important metaphysical lessons that are often presented as derived from two new scientific disciplines: synthetic biology and neuroscience. I analyse four of them: the nature of life, the existence of a soul (the mind-body problem), personhood, and free will. Many caveats are in order, and each 'advance' or each case should be assessed for itself. I conclude that a main lesson can nevertheless be learned: in conjunction with modern science, neuroscience and synthetic biology allow us to enrich old metaphysical debates, to deepen and even renew them. In particular, it becomes less and less plausible to consider life, mind, person, and agency as non-natural or non-physical entities. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

FDA 101: Regulating Biological Products

MedlinePlus

... Home For Consumers Consumer Updates FDA 101: Regulating Biological Products Share Tweet Linkedin Pin it More sharing ... about this diverse and highly important field. What biological products does FDA regulate? The Center for Biologics ...

Nanomaterial interactions with biomembranes: Bridging the gap between soft matter models and biological context.

PubMed

Werner, Marco; Auth, Thorsten; Beales, Paul A; Fleury, Jean Baptiste; Höök, Fredrik; Kress, Holger; Van Lehn, Reid C; Müller, Marcus; Petrov, Eugene P; Sarkisov, Lev; Sommer, Jens-Uwe; Baulin, Vladimir A

2018-04-03

Synthetic polymers, nanoparticles, and carbon-based materials have great potential in applications including drug delivery, gene transfection, in vitro and in vivo imaging, and the alteration of biological function. Nature and humans use different design strategies to create nanomaterials: biological objects have emerged from billions of years of evolution and from adaptation to their environment resulting in high levels of structural complexity; in contrast, synthetic nanomaterials result from minimalistic but controlled design options limited by the authors' current understanding of the biological world. This conceptual mismatch makes it challenging to create synthetic nanomaterials that possess desired functions in biological media. In many biologically relevant applications, nanomaterials must enter the cell interior to perform their functions. An essential transport barrier is the cell-protecting plasma membrane and hence the understanding of its interaction with nanomaterials is a fundamental task in biotechnology. The authors present open questions in the field of nanomaterial interactions with biological membranes, including: how physical mechanisms and molecular forces acting at the nanoscale restrict or inspire design options; which levels of complexity to include next in computational and experimental models to describe how nanomaterials cross barriers via passive or active processes; and how the biological media and protein corona interfere with nanomaterial functionality. In this Perspective, the authors address these questions with the aim of offering guidelines for the development of next-generation nanomaterials that function in biological media.

Eugene – A Domain Specific Language for Specifying and Constraining Synthetic Biological Parts, Devices, and Systems

PubMed Central

Bilitchenko, Lesia; Liu, Adam; Cheung, Sherine; Weeding, Emma; Xia, Bing; Leguia, Mariana; Anderson, J. Christopher; Densmore, Douglas

2011-01-01

Background Synthetic biological systems are currently created by an ad-hoc, iterative process of specification, design, and assembly. These systems would greatly benefit from a more formalized and rigorous specification of the desired system components as well as constraints on their composition. Therefore, the creation of robust and efficient design flows and tools is imperative. We present a human readable language (Eugene) that allows for the specification of synthetic biological designs based on biological parts, as well as provides a very expressive constraint system to drive the automatic creation of composite Parts (Devices) from a collection of individual Parts. Results We illustrate Eugene's capabilities in three different areas: Device specification, design space exploration, and assembly and simulation integration. These results highlight Eugene's ability to create combinatorial design spaces and prune these spaces for simulation or physical assembly. Eugene creates functional designs quickly and cost-effectively. Conclusions Eugene is intended for forward engineering of DNA-based devices, and through its data types and execution semantics, reflects the desired abstraction hierarchy in synthetic biology. Eugene provides a powerful constraint system which can be used to drive the creation of new devices at runtime. It accomplishes all of this while being part of a larger tool chain which includes support for design, simulation, and physical device assembly. PMID:21559524

76 FR 11075 - Schedules of Controlled Substances: Temporary Placement of Five Synthetic Cannabinoids Into...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-01

... of Abuse A ``cannabinoid'' is a class of chemical compounds in the marijuana plant that are... constituent of marijuana. ``Synthetic cannabinoids'' are a large family of chemically unrelated structures functionally (biologically) similar to THC, the active principle of marijuana. Two of the five synthetic...

Advancing secondary metabolite biosynthesis in yeast with synthetic biology tools.

PubMed

Siddiqui, Michael S; Thodey, Kate; Trenchard, Isis; Smolke, Christina D

2012-03-01

Secondary metabolites are an important source of high-value chemicals, many of which exhibit important pharmacological properties. These valuable natural products are often difficult to synthesize chemically and are commonly isolated through inefficient extractions from natural biological sources. As such, they are increasingly targeted for production by biosynthesis from engineered microorganisms. The budding yeast species Saccharomyces cerevisiae has proven to be a powerful microorganism for heterologous expression of biosynthetic pathways. S. cerevisiae's usefulness as a host organism is owed in large part to the wealth of knowledge accumulated over more than a century of intense scientific study. Yet many challenges are currently faced in engineering yeast strains for the biosynthesis of complex secondary metabolite production. However, synthetic biology is advancing the development of new tools for constructing, controlling, and optimizing complex metabolic pathways in yeast. Here, we review how the coupling between yeast biology and synthetic biology is advancing the use of S. cerevisiae as a microbial host for the construction of secondary metabolic pathways. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

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.

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.

Bacteriophage-based synthetic biology for the study of infectious diseases

PubMed Central

Lu, Timothy K.

2014-01-01

Since their discovery, bacteriophages have contributed enormously to our understanding of molecular biology as model systems. Furthermore, bacteriophages have provided many tools that have advanced the fields of genetic engineering and synthetic biology. Here, we discuss bacteriophage-based technologies and their application to the study of infectious diseases. New strategies for engineering genomes have the potential to accelerate the design of novel phages as therapies, diagnostics, and tools. Though almost a century has elapsed since their discovery, bacteriophages continue to have a major impact on modern biological sciences, especially with the growth of multidrug-resistant bacteria and interest in the microbiome. PMID:24997401

Synthetic Aziridines in Medicinal Chemistry: A Mini-Review.

PubMed

Singh, Girija S

2016-01-01

Azaheterocyclic compounds are well-known to have diverse types of biological activity. Among them, azacyclopropanes, commonly referred as aziridines, occupy a prominent place in synthetic organic and medicinal chemistry due to its occurrence in natural resources, complexity involved in synthesis due to ring-strain, building blocks in organic synthesis, and its biological properties. Several novel compounds containing aziridine ring have been designed and synthesized recently by medicinal chemists for evaluating their biological profile. A number of compounds are reported as cysteine protease inhibitors, antibacterial, antifungal, anticancer, antileishmanial, and antimalarial agents. This review article summarizes the biological activity of such compounds. The preparation of such compounds is also described.

Synthetic Biology and Metabolic Engineering for Marine Carotenoids: New Opportunities and Future Prospects

PubMed Central

Wang, Chonglong; Kim, Jung-Hun; Kim, Seon-Won

2014-01-01

Carotenoids are a class of diverse pigments with important biological roles such as light capture and antioxidative activities. Many novel carotenoids have been isolated from marine organisms to date and have shown various utilizations as nutraceuticals and pharmaceuticals. In this review, we summarize the pathways and enzymes of carotenoid synthesis and discuss various modifications of marine carotenoids. The advances in metabolic engineering and synthetic biology for carotenoid production are also reviewed, in hopes that this review will promote the exploration of marine carotenoid for their utilizations. PMID:25233369

News: Synthetic biology leading to specialty chemicals ...

EPA Pesticide Factsheets

Synthetic biology can combine the disciplines of biology, engineering, and chemistry productively to form molecules of great scientific and commercial value. Recent advances in the new field are explored for their connection to new tools that have been used to elucidate production pathways to a wide variety of chemicals generated by microorganisms. The selection and enhancement of microbiological strains through the practice of strain engineering enables targets of design, construction, and optimization. This news column aspires to cover recent literature relating to the development and understanding of clean technology.

Programming Morphogenesis through Systems and Synthetic Biology.

PubMed

Velazquez, Jeremy J; Su, Emily; Cahan, Patrick; Ebrahimkhani, Mo R

2018-04-01

Mammalian tissue development is an intricate, spatiotemporal process of self-organization that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell-cell interactions to enable the reliable and robust engineering of morphogenesis. Here, we review advances in synthetic biology, single cell genomics, and multiscale modeling, which, when synthesized, provide a framework to achieve the ambitious goal of programming morphogenesis in complex tissues and organoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthetic biology and metabolic engineering for marine carotenoids: new opportunities and future prospects.

PubMed

Wang, Chonglong; Kim, Jung-Hun; Kim, Seon-Won

2014-09-17

Carotenoids are a class of diverse pigments with important biological roles such as light capture and antioxidative activities. Many novel carotenoids have been isolated from marine organisms to date and have shown various utilizations as nutraceuticals and pharmaceuticals. In this review, we summarize the pathways and enzymes of carotenoid synthesis and discuss various modifications of marine carotenoids. The advances in metabolic engineering and synthetic biology for carotenoid production are also reviewed, in hopes that this review will promote the exploration of marine carotenoid for their utilizations.

Designing synthetic networks in silico: a generalised evolutionary algorithm approach.

PubMed

Smith, Robert W; van Sluijs, Bob; Fleck, Christian

2017-12-02

Evolution has led to the development of biological networks that are shaped by environmental signals. Elucidating, understanding and then reconstructing important network motifs is one of the principal aims of Systems & Synthetic Biology. Consequently, previous research has focused on finding optimal network structures and reaction rates that respond to pulses or produce stable oscillations. In this work we present a generalised in silico evolutionary algorithm that simultaneously finds network structures and reaction rates (genotypes) that can satisfy multiple defined objectives (phenotypes). The key step to our approach is to translate a schema/binary-based description of biological networks into systems of ordinary differential equations (ODEs). The ODEs can then be solved numerically to provide dynamic information about an evolved networks functionality. Initially we benchmark algorithm performance by finding optimal networks that can recapitulate concentration time-series data and perform parameter optimisation on oscillatory dynamics of the Repressilator. We go on to show the utility of our algorithm by finding new designs for robust synthetic oscillators, and by performing multi-objective optimisation to find a set of oscillators and feed-forward loops that are optimal at balancing different system properties. In sum, our results not only confirm and build on previous observations but we also provide new designs of synthetic oscillators for experimental construction. In this work we have presented and tested an evolutionary algorithm that can design a biological network to produce desired output. Given that previous designs of synthetic networks have been limited to subregions of network- and parameter-space, the use of our evolutionary optimisation algorithm will enable Synthetic Biologists to construct new systems with the potential to display a wider range of complex responses.

21 CFR 607.30 - Updating blood product listing information.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Updating blood product listing information. 607.30... (CONTINUED) BIOLOGICS ESTABLISHMENT REGISTRATION AND PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.30 Updating blood product...

21 CFR 607.30 - Updating blood product listing information.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Updating blood product listing information. 607.30... (CONTINUED) BIOLOGICS ESTABLISHMENT REGISTRATION AND PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.30 Updating blood product...

21 CFR 607.30 - Updating blood product listing information.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Updating blood product listing information. 607.30... (CONTINUED) BIOLOGICS ESTABLISHMENT REGISTRATION AND PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.30 Updating blood product...

21 CFR 607.30 - Updating blood product listing information.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Updating blood product listing information. 607.30... (CONTINUED) BIOLOGICS ESTABLISHMENT REGISTRATION AND PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.30 Updating blood product...

21 CFR 607.30 - Updating blood product listing information.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Updating blood product listing information. 607.30... (CONTINUED) BIOLOGICS ESTABLISHMENT REGISTRATION AND PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.30 Updating blood product...

Robustness of synthetic oscillators in growing and dividing cells

NASA Astrophysics Data System (ADS)

Paijmans, Joris; Lubensky, David K.; Rein ten Wolde, Pieter

2017-05-01

Synthetic biology sets out to implement new functions in cells, and to develop a deeper understanding of biological design principles. Elowitz and Leibler [Nature (London) 403, 335 (2000), 10.1038/35002125] showed that by rational design of the reaction network, and using existing biological components, they could create a network that exhibits periodic gene expression, dubbed the repressilator. More recently, Stricker et al. [Nature (London) 456, 516 (2008), 10.1038/nature07389] presented another synthetic oscillator, called the dual-feedback oscillator, which is more stable. Detailed studies have been carried out to determine how the stability of these oscillators is affected by the intrinsic noise of the interactions between the components and the stochastic expression of their genes. However, as all biological oscillators reside in growing and dividing cells, an important question is how these oscillators are perturbed by the cell cycle. In previous work we showed that the periodic doubling of the gene copy numbers due to DNA replication can couple not only natural, circadian oscillators to the cell cycle [Paijmans et al., Proc. Natl. Acad. Sci. (USA) 113, 4063 (2016), 10.1073/pnas.1507291113], but also these synthetic oscillators. Here we expand this study. We find that the strength of the locking between oscillators depends not only on the positions of the genes on the chromosome, but also on the noise in the timing of gene replication: noise tends to weaken the coupling. Yet, even in the limit of high levels of noise in the replication times of the genes, both synthetic oscillators show clear signatures of locking to the cell cycle. This work enhances our understanding of the design of robust biological oscillators inside growing and diving cells.

Establishing Chlamydomonas reinhardtii as an industrial biotechnology host

PubMed Central

Scaife, Mark A; Nguyen, Ginnie TDT; Rico, Juan; Lambert, Devinn; Helliwell, Katherine E; Smith, Alison G

2015-01-01

Microalgae constitute a diverse group of eukaryotic unicellular organisms that are of interest for pure and applied research. Owing to their natural synthesis of value-added natural products microalgae are emerging as a source of sustainable chemical compounds, proteins and metabolites, including but not limited to those that could replace compounds currently made from fossil fuels. For the model microalga, Chlamydomonas reinhardtii, this has prompted a period of rapid development so that this organism is poised for exploitation as an industrial biotechnology platform. The question now is how best to achieve this? Highly advanced industrial biotechnology systems using bacteria and yeasts were established in a classical metabolic engineering manner over several decades. However, the advent of advanced molecular tools and the rise of synthetic biology provide an opportunity to expedite the development of C. reinhardtii as an industrial biotechnology platform, avoiding the process of incremental improvement. In this review we describe the current status of genetic manipulation of C. reinhardtii for metabolic engineering. We then introduce several concepts that underpin synthetic biology, and show how generic parts are identified and used in a standard manner to achieve predictable outputs. Based on this we suggest that the development of C. reinhardtii as an industrial biotechnology platform can be achieved more efficiently through adoption of a synthetic biology approach. Significance Statement Chlamydomonas reinhardtii offers potential as a host for the production of high value compounds for industrial biotechnology. Synthetic biology provides a mechanism to generate generic, well characterised tools for application in the rational genetic manipulation of organisms: if synthetic biology principles were adopted for manipulation of C. reinhardtii, development of this microalga as an industrial biotechnology platform would be expedited. PMID:25641561

Biotechnology and synthetic biology approaches for metabolic engineering of bioenergy crops.

PubMed

Shih, Patrick M; Liang, Yan; Loqué, Dominique

2016-07-01

The Green Revolution has fuelled an exponential growth in human population since the mid-20th century. Due to population growth, food and energy demands will soon surpass supply capabilities. To overcome these impending problems, significant improvements in genetic engineering will be needed to complement breeding efforts in order to accelerate the improvement of agronomical traits. The new field of plant synthetic biology has emerged in recent years and is expected to support rapid, precise, and robust engineering of plants. In this review, we present recent advances made in the field of plant synthetic biology, specifically in genome editing, transgene expression regulation, and bioenergy crop engineering, with a focus on traits related to lignocellulose, oil, and soluble sugars. Ultimately, progress and innovation in these fields may facilitate the development of beneficial traits in crop plants to meet society's bioenergy needs. © 2016 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

A novel cell autolysis system for cost-competitive downstream processing.

PubMed

Hajnal, Ivan; Chen, Xiangbin; Chen, Guo-Qiang

2016-11-01

The industrial production of low value-added biological products poses significant challenges due to cost pressures. In recent years, it has been argued that synthetic biology approaches will lead to breakthroughs that eliminate price bottlenecks for the production of a wide range of biological products including bioplastics and biofuels. One significant bottleneck lies in the necessity to break the tough cell walls of microbes in order to release intracellular products. We here report the implementation of the first synthetic biology standard part based on the lambda phage SRRz genes and a synthetic ribosome binding site (RBS) that works in Escherichia coli and Halomonas campaniensis, which enables the producer strains to induce lysis after the addition of small amounts (1-5 %) of solvents or to spontaneously lyse during the stresses of downstream processing, and thus has the potential to eliminate the mechanical cell disruption step as both an efficiency bottleneck and a significant capex barrier when implementing downstream bioprocesses.

Societal impact of synthetic biology: responsible research and innovation (RRI).

PubMed

Gregorowius, Daniel; Deplazes-Zemp, Anna

2016-11-30

Synthetic biology is an emerging field at the interface between biology and engineering, which has generated many expectations for beneficial biomedical and biotechnological applications. At the same time, however, it has also raised concerns about risks or the aim of producing new forms of living organisms. Researchers from different disciplines as well as policymakers and the general public have expressed the need for a form of technology assessment that not only deals with technical aspects, but also includes societal and ethical issues. A recent and very influential model of technology assessment that tries to implement these aims is known as RRI (Responsible Research and Innovation). In this paper, we introduce this model and its historical precursor strategies. Based on the societal and ethical issues which are presented in the current literature, we discuss challenges and opportunities of applying the RRI model for the assessment of synthetic biology. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

High Throughput Assay for Bacterial Adhesion on Acellular Dermal Matrices and Synthetic Surgical Materials

PubMed Central

Nyame, Theodore T.; Lemon, Katherine P.; Kolter, Roberto; Liao, Eric C.

2013-01-01

Background There has been increasing use of various synthetic and biologically derived materials in surgery. Biologic surgical materials are used in many plastic surgery procedures, ranging from breast reconstruction to hernia repairs. In particular, acellular dermal matrix (ADM) material has gained popularity in these applications. There is a paucity of data on how ADM compares to other surgical materials as a substrate for bacterial adhesion, the first step in formation biofilm, which occurs in prosthetic wound infections. We have designed a high throughput assay to evaluate Staphylococcus aureus adherence on various synthetic and biologically derived materials. Methods Clinical isolates of Staphylococcus aureus (strains SC-1 and UAMS-1) were cultured with different materials and bacterial adherence was measured using a resazurin cell vitality reporter microtiter assay. Four materials that are commonly utilized in reconstructive procedures were evaluated: prolene mesh, vicryl mesh, and two different ADM preparations (AlloDerm®, FlexHD®). We were able to develop a high throughput and reliable assay for quantifying bacterial adhesion on synthetic and biologically derived materials. Results The resazurin vitality assay can be reliably used to quantify bacterial adherence to acellular dermal matrix material, as well as synthetic material. S. aureus strains SC-1 and UAMS-1 both adhered better to ADM materials (AlloDerm® vs. FlexHD®) than to the synthetic material prolene. S. aureus also adhered better to vicryl than to prolene. Strain UAMS-1 adhered better to vicryl and ADM materials than did strain SC-1. Conclusion Our results suggest that S. aureus adheres more readily to ADM material than to synthetic material. We have developed an assay to rapidly test bacterial formation on surgical materials, using two S. aureus bacterial strains. This provides a standard method to evaluate existing and new materials with regard to bacterial adherence and potential propensity for infection. This assay is particularly important in the clinical context of the severe sequelae of post-operative infection. PMID:22030489

A novel edge-preserving nonnegative matrix factorization method for spectral unmixing

NASA Astrophysics Data System (ADS)

Bao, Wenxing; Ma, Ruishi

2015-12-01

Spectral unmixing technique is one of the key techniques to identify and classify the material in the hyperspectral image processing. A novel robust spectral unmixing method based on nonnegative matrix factorization(NMF) is presented in this paper. This paper used an edge-preserving function as hypersurface cost function to minimize the nonnegative matrix factorization. To minimize the hypersurface cost function, we constructed the updating functions for signature matrix of end-members and abundance fraction respectively. The two functions are updated alternatively. For evaluation purpose, synthetic data and real data have been used in this paper. Synthetic data is used based on end-members from USGS digital spectral library. AVIRIS Cuprite dataset have been used as real data. The spectral angle distance (SAD) and abundance angle distance(AAD) have been used in this research for assessment the performance of proposed method. The experimental results show that this method can obtain more ideal results and good accuracy for spectral unmixing than present methods.

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.

Synthetic and semi-synthetic chondroitin sulfate oligosaccharides, polysaccharides, and glycomimetics.

PubMed

Bedini, Emiliano; Parrilli, Michelangelo

2012-07-15

Chondroitin sulfate (CS) is a sulfated polysaccharide involved in a myriad of biological processes. Due to the variable sulfation pattern of CS polymer chains, the need to study in detail structure-activity relationships regarding CS biomedical features has provoked much interest in obtaining synthetic CS species. This paper reviews two decades of synthetic and semi-synthetic CS oligosaccharides, polysaccharides, and glycomimetics obtained by chemical, chemoenzymatic, enzymatic, and microbiological-chemical strategies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Synthetic constructs in/for the environment: Managing the interplay between natural and engineered Biology

PubMed Central

Schmidt, Markus; de Lorenzo, Víctor

2012-01-01

The plausible release of deeply engineered or even entirely synthetic/artificial microorganisms raises the issue of their intentional (e.g. bioremediation) or accidental interaction with the Environment. Containment systems designed in the 1980s–1990s for limiting the spread of genetically engineered bacteria and their recombinant traits are still applicable to contemporary Synthetic Biology constructs. Yet, the ease of DNA synthesis and the uncertainty on how non-natural properties and strains could interplay with the existing biological word poses yet again the challenge of designing safe and efficacious firewalls to curtail possible interactions. Such barriers may include xeno-nucleic acids (XNAs) instead of DNA as information-bearing molecules, rewriting the genetic code to make it non-understandable by the existing gene expression machineries, and/or making growth dependent on xenobiotic chemicals. PMID:22710182

Uncritical and unbalanced coverage of synthetic biology in the Nordic press.

PubMed

Ancillotti, Mirko; Holmberg, Niklas; Lindfelt, Mikael; Eriksson, Stefan

2017-02-01

Synthetic biology will probably have a high impact on a variety of fields, such as healthcare, environment, biofuels, agriculture, and so on. A driving theme in European research policy is the importance of maintaining public legitimacy and support. Media can influence public attitudes and are therefore an important object of study. Through qualitative content analysis, this study investigates the press coverage of synthetic biology in the major Nordic countries between 2009 and 2014. The press coverage was found to be event-driven and there were striking similarities between countries when it comes to framing, language use, and treated themes. Reporters showed a marked dependence on their sources, mainly scientists and stakeholders, who thus drives the media agenda. The media portrayal was very positive, with an optimistic look at future benefits and very little discussion of possible risks.

Literature classification for semi-automated updating of biological knowledgebases

PubMed Central

2013-01-01

Background As the output of biological assays increase in resolution and volume, the body of specialized biological data, such as functional annotations of gene and protein sequences, enables extraction of higher-level knowledge needed for practical application in bioinformatics. Whereas common types of biological data, such as sequence data, are extensively stored in biological databases, functional annotations, such as immunological epitopes, are found primarily in semi-structured formats or free text embedded in primary scientific literature. Results We defined and applied a machine learning approach for literature classification to support updating of TANTIGEN, a knowledgebase of tumor T-cell antigens. Abstracts from PubMed were downloaded and classified as either "relevant" or "irrelevant" for database update. Training and five-fold cross-validation of a k-NN classifier on 310 abstracts yielded classification accuracy of 0.95, thus showing significant value in support of data extraction from the literature. Conclusion We here propose a conceptual framework for semi-automated extraction of epitope data embedded in scientific literature using principles from text mining and machine learning. The addition of such data will aid in the transition of biological databases to knowledgebases. PMID:24564403

At the biological modeling and simulation frontier.

PubMed

Hunt, C Anthony; Ropella, Glen E P; Lam, Tai Ning; Tang, Jonathan; Kim, Sean H J; Engelberg, Jesse A; Sheikh-Bahaei, Shahab

2009-11-01

We provide a rationale for and describe examples of synthetic modeling and simulation (M&S) of biological systems. We explain how synthetic methods are distinct from familiar inductive methods. Synthetic M&S is a means to better understand the mechanisms that generate normal and disease-related phenomena observed in research, and how compounds of interest interact with them to alter phenomena. An objective is to build better, working hypotheses of plausible mechanisms. A synthetic model is an extant hypothesis: execution produces an observable mechanism and phenomena. Mobile objects representing compounds carry information enabling components to distinguish between them and react accordingly when different compounds are studied simultaneously. We argue that the familiar inductive approaches contribute to the general inefficiencies being experienced by pharmaceutical R&D, and that use of synthetic approaches accelerates and improves R&D decision-making and thus the drug development process. A reason is that synthetic models encourage and facilitate abductive scientific reasoning, a primary means of knowledge creation and creative cognition. When synthetic models are executed, we observe different aspects of knowledge in action from different perspectives. These models can be tuned to reflect differences in experimental conditions and individuals, making translational research more concrete while moving us closer to personalized medicine.

A System-Level Pathway-Phenotype Association Analysis Using Synthetic Feature Random Forest

PubMed Central

Pan, Qinxin; Hu, Ting; Malley, James D.; Andrew, Angeline S.; Karagas, Margaret R.; Moore, Jason H.

2015-01-01

As the cost of genome-wide genotyping decreases, the number of genome-wide association studies (GWAS) has increased considerably. However, the transition from GWAS findings to the underlying biology of various phenotypes remains challenging. As a result, due to its system-level interpretability, pathway analysis has become a popular tool for gaining insights on the underlying biology from high-throughput genetic association data. In pathway analyses, gene sets representing particular biological processes are tested for significant associations with a given phenotype. Most existing pathway analysis approaches rely on single-marker statistics and assume that pathways are independent of each other. As biological systems are driven by complex biomolecular interactions, embracing the complex relationships between single-nucleotide polymorphisms (SNPs) and pathways needs to be addressed. To incorporate the complexity of gene-gene interactions and pathway-pathway relationships, we propose a system-level pathway analysis approach, synthetic feature random forest (SF-RF), which is designed to detect pathway-phenotype associations without making assumptions about the relationships among SNPs or pathways. In our approach, the genotypes of SNPs in a particular pathway are aggregated into a synthetic feature representing that pathway via Random Forest (RF). Multiple synthetic features are analyzed using RF simultaneously and the significance of a synthetic feature indicates the significance of the corresponding pathway. We further complement SF-RF with pathway-based Statistical Epistasis Network (SEN) analysis that evaluates interactions among pathways. By investigating the pathway SEN, we hope to gain additional insights into the genetic mechanisms contributing to the pathway-phenotype association. We apply SF-RF to a population-based genetic study of bladder cancer and further investigate the mechanisms that help explain the pathway-phenotype associations using SEN. The bladder cancer associated pathways we found are both consistent with existing biological knowledge and reveal novel and plausible hypotheses for future biological validations. PMID:24535726

Coupling Spatial Segregation with Synthetic Circuits to Control Bacterial Survival (Open Access)

DTIC Science & Technology

2016-02-29

Subject Categories Synthetic Biology & Biotechnology; Quantitative Biology & Dynamical Systems DOI 10.15252/msb.20156567 | Received 9 September 2015...survival. Experimentally , we program collective survival using three different gene circuits, which allow us to evaluate the modularity of the...QS-CAT circuit depends on QS regulation. The QS-BlaM circuit depends on both QS regulation and enzyme release (by lysis and export). G–I Experimental

Design Automation in Synthetic Biology.

PubMed

Appleton, Evan; Madsen, Curtis; Roehner, Nicholas; Densmore, Douglas

2017-04-03

Design automation refers to a category of software tools for designing systems that work together in a workflow for designing, building, testing, and analyzing systems with a target behavior. In synthetic biology, these tools are called bio-design automation (BDA) tools. In this review, we discuss the BDA tools areas-specify, design, build, test, and learn-and introduce the existing software tools designed to solve problems in these areas. We then detail the functionality of some of these tools and show how they can be used together to create the desired behavior of two types of modern synthetic genetic regulatory networks. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Recent advances of molecular toolbox construction expand Pichia pastoris in synthetic biology applications.

PubMed

Kang, Zhen; Huang, Hao; Zhang, Yunfeng; Du, Guocheng; Chen, Jian

2017-01-01

Pichia pastoris: (reclassified as Komagataella phaffii), a methylotrophic yeast strain has been widely used for heterologous protein production because of its unique advantages, such as readily achievable high-density fermentation, tractable genetic modifications and typical eukaryotic post-translational modifications. More recently, P. pastoris as a metabolic pathway engineering platform has also gained much attention. In this mini-review, we addressed recent advances of molecular toolboxes, including synthetic promoters, signal peptides, and genome engineering tools that established for P. pastoris. Furthermore, the applications of P. pastoris towards synthetic biology were also discussed and prospected especially in the context of genome-scale metabolic pathway analysis.

Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry

PubMed Central

Miles, John J.; Tan, Mai Ping; Dolton, Garry; Galloway, Sarah A.E.; Laugel, Bruno; Makinde, Julia; Matthews, Katherine K.; Watkins, Thomas S.; Wong, Yide; Clark, Richard J.; Pentier, Johanne M.; Attaf, Meriem; Lissina, Anya; Ager, Ann; Gallimore, Awen; Gras, Stephanie; Rossjohn, Jamie; Burrows, Scott R.; Cole, David K.; Price, David A.

2018-01-01

Polypeptide vaccines effectively activate human T cells but suffer from poor biological stability, which confines both transport logistics and in vivo therapeutic activity. Synthetic biology has the potential to address these limitations through the generation of highly stable antigenic “mimics” using subunits that do not exist in the natural world. We developed a platform based on D–amino acid combinatorial chemistry and used this platform to reverse engineer a fully artificial CD8+ T cell agonist that mirrored the immunogenicity profile of a native epitope blueprint from influenza virus. This nonnatural peptide was highly stable in human serum and gastric acid, reflecting an intrinsic resistance to physical and enzymatic degradation. In vitro, the synthetic agonist stimulated and expanded an archetypal repertoire of polyfunctional human influenza virus–specific CD8+ T cells. In vivo, specific responses were elicited in naive humanized mice by subcutaneous vaccination, conferring protection from subsequent lethal influenza challenge. Moreover, the synthetic agonist was immunogenic after oral administration. This proof-of-concept study highlights the power of synthetic biology to expand the horizons of vaccine design and therapeutic delivery. PMID:29528337

Playing God and the intrinsic value of life: moral problems for synthetic biology?

PubMed

Link, Hans-Jürgen

2013-06-01

Most of the reports on synthetic biology include not only familiar topics like biosafety and biosecurity but also a chapter on 'ethical concerns'; a variety of diffuse topics that are interrelated in some way or another. This article deals with these 'ethical concerns'. In particular it addresses issues such as the intrinsic value of life and how to deal with 'artificial life', and the fear that synthetic biologists are tampering with nature or playing God. Its aim is to analyse what exactly is the nature of the concerns and what rationale may lie behind them. The analysis concludes that the above-mentioned worries do not give genuine cause for serious concern. In the best possible way they are interpreted as slippery slope arguments, yet arguments of this type need to be handled with care. It is argued that although we are urged to be especially vigilant we do not have sufficiently cogent reasons to assume that synthetic biology will cause such fundamental hazards as to warrant restricting or refraining from research in this field.

Machine metaphors and ethics in synthetic biology.

PubMed

Boldt, Joachim

2018-06-04

The extent to which machine metaphors are used in synthetic biology is striking. These metaphors contain a specific perspective on organisms as well as on scientific and technological progress. Expressions such as "genetically engineered machine", "genetic circuit", and "platform organism", taken from the realms of electronic engineering, car manufacturing, and information technology, highlight specific aspects of the functioning of living beings while at the same time hiding others, such as evolutionary change and interdependencies in ecosystems. Since these latter aspects are relevant for, for example, risk evaluation of uncontained uses of synthetic organisms, it is ethically imperative to resist the thrust of machine metaphors in this respect. In addition, from the perspective of the machine metaphor viewing an entity as a moral agent or patient becomes dubious. If one were to regard living beings, including humans, as machines, it becomes difficult to justify ascriptions of moral status. Finally, the machine metaphor reinforces beliefs in the potential of synthetic biology to play a decisive role in solving societal problems, and downplays the role of alternative technological, and social and political measures.

Morphology-Controlled Synthesis of Rhodium Nanoparticles for Cancer Phototherapy.

PubMed

Kang, Seounghun; Shin, Woojun; Choi, Myung-Ho; Ahn, Minchul; Kim, Young-Kwan; Kim, Seongchan; Min, Dal-Hee; Jang, Hongje

2018-06-22

Rhodium nanoparticles are promising transition metal nanocatalysts for electrochemical and synthetic organic chemistry applications. However, notwithstanding their potential, to date, Rh nanoparticles have not been utilized for biological applications; there has been no cytotoxicity study of Rh reported in the literature. In this regard, the absence of a facile and controllable synthetic strategy of Rh nanostructures with various sizes and morphologies might be responsible for the lack of progress in this field. Herein, we have developed a synthetic strategy for Rh nanostructures with controllable morphology through an inverse-directional galvanic replacement reaction. Three types of Rh-based nanostructures-nanoshells, nanoframes, and porous nanoplates-were successfully synthesized. A plausible synthetic mechanism based on thermodynamic considerations has also been proposed. The cytotoxicity, surface functionalization, and photothermal therapeutic effect of manufactured Rh nanostructures were systematically investigated to reveal their potential for in vitro and in vivo biological applications. Considering the comparable behavior of porous Rh nanoplates to that of gold nanostructures that are widely used in nanomedicine, the present study introduces Rh-based nanostructures into the field of biological research.

Dealing with the genetic load in bacterial synthetic biology circuits: convergences with the Ohm's law

PubMed Central

Carbonell-Ballestero, M.; Garcia-Ramallo, E.; Montañez, R.; Rodriguez-Caso, C.; Macía, J.

2016-01-01

Synthetic biology seeks to envision living cells as a matter of engineering. However, increasing evidence suggests that the genetic load imposed by the incorporation of synthetic devices in a living organism introduces a sort of unpredictability in the design process. As a result, individual part characterization is not enough to predict the behavior of designed circuits and thus, a costly trial-error process is eventually required. In this work, we provide a new theoretical framework for the predictive treatment of the genetic load. We mathematically and experimentally demonstrate that dependences among genes follow a quantitatively predictable behavior. Our theory predicts the observed reduction of the expression of a given synthetic gene when an extra genetic load is introduced in the circuit. The theory also explains that such dependence qualitatively differs when the extra load is added either by transcriptional or translational modifications. We finally show that the limitation of the cellular resources for gene expression leads to a mathematical formulation that converges to an expression analogous to the Ohm's law for electric circuits. Similitudes and divergences with this law are outlined. Our work provides a suitable framework with predictive character for the design process of complex genetic devices in synthetic biology. PMID:26656950

BioNetCAD: design, simulation and experimental validation of synthetic biochemical networks

PubMed Central

Rialle, Stéphanie; Felicori, Liza; Dias-Lopes, Camila; Pérès, Sabine; El Atia, Sanaâ; Thierry, Alain R.; Amar, Patrick; Molina, Franck

2010-01-01

Motivation: Synthetic biology studies how to design and construct biological systems with functions that do not exist in nature. Biochemical networks, although easier to control, have been used less frequently than genetic networks as a base to build a synthetic system. To date, no clear engineering principles exist to design such cell-free biochemical networks. Results: We describe a methodology for the construction of synthetic biochemical networks based on three main steps: design, simulation and experimental validation. We developed BioNetCAD to help users to go through these steps. BioNetCAD allows designing abstract networks that can be implemented thanks to CompuBioTicDB, a database of parts for synthetic biology. BioNetCAD enables also simulations with the HSim software and the classical Ordinary Differential Equations (ODE). We demonstrate with a case study that BioNetCAD can rationalize and reduce further experimental validation during the construction of a biochemical network. Availability and implementation: BioNetCAD is freely available at http://www.sysdiag.cnrs.fr/BioNetCAD. It is implemented in Java and supported on MS Windows. CompuBioTicDB is freely accessible at http://compubiotic.sysdiag.cnrs.fr/ Contact: stephanie.rialle@sysdiag.cnrs.fr; franck.molina@sysdiag.cnrs.fr Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20628073

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.

Micro/nanofabricated environments for synthetic biology.

PubMed

Collier, C Patrick; Simpson, Michael L

2011-08-01

A better understanding of how confinement, crowding and reduced dimensionality modulate reactivity and reaction dynamics will aid in the rational and systematic discovery of functionality in complex biological systems. Artificial microfabricated and nanofabricated structures have helped elucidate the effects of nanoscale spatial confinement and segregation on biological behavior, particularly when integrated with microfluidics, through precise control in both space and time of diffusible signals and binding interactions. Examples of nanostructured interfaces for synthetic biology include the development of cell-like compartments for encapsulating biochemical reactions, nanostructured environments for fundamental studies of diffusion, molecular transport and biochemical reaction kinetics, and regulation of biomolecular interactions as functions of microfabricated and nanofabricated topological constraints. Copyright © 2011 Elsevier Ltd. All rights reserved.

Towards the Development of Synthetic Antibiotics: Designs Inspired by Natural Antimicrobial Peptides.

PubMed

Azmi, Fazren; Skwarczynski, Mariusz; Toth, Istvan

2016-01-01

Virtually every living organism produces gene-encoded antimicrobial peptides (AMPs) that provide an immediate defence against pathogen invasion. Many AMPs have been isolated and used as antibiotics that are effective against multidrug-resistant bacteria. Although encouraging, AMPs have such poor drug-like properties that their application for clinical use is restricted. In turn, this has diverted research to the development of synthetic molecules that retain the therapeutic efficacy of AMPs but are endowed with greater biological stability and safety profiles. Most of the synthetic molecules, either based on a peptidic or non-peptidic scaffold, have been designed to mimic the amphiphilic properties of native AMPs, which are widely believed to be the key determinant of their antibacterial activity. In this review, the structural, chemical and biophysical features that govern the biological activities of various synthetic designs are discussed extensively. Recent innovative approaches from the literature that exhibit novel concepts towards the development of new synthetic antibacterial agents, including the engineered delivery platform incorporated with AMP mimetics, are also emphasised.

Quantitative characterization of genetic parts and circuits for plant synthetic biology.

PubMed

Schaumberg, Katherine A; Antunes, Mauricio S; Kassaw, Tessema K; Xu, Wenlong; Zalewski, Christopher S; Medford, June I; Prasad, Ashok

2016-01-01

Plant synthetic biology promises immense technological benefits, including the potential development of a sustainable bio-based economy through the predictive design of synthetic gene circuits. Such circuits are built from quantitatively characterized genetic parts; however, this characterization is a significant obstacle in work with plants because of the time required for stable transformation. We describe a method for rapid quantitative characterization of genetic plant parts using transient expression in protoplasts and dual luciferase outputs. We observed experimental variability in transient-expression assays and developed a mathematical model to describe, as well as statistical normalization methods to account for, this variability, which allowed us to extract quantitative parameters. We characterized >120 synthetic parts in Arabidopsis and validated our method by comparing transient expression with expression in stably transformed plants. We also tested >100 synthetic parts in sorghum (Sorghum bicolor) protoplasts, and the results showed that our method works in diverse plant groups. Our approach enables the construction of tunable gene circuits in complex eukaryotic organisms.

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.

Identification of line-specific strategies for improving carotenoid production in synthetic maize through data-driven mathematical modeling.

PubMed

Comas, Jorge; Benfeitas, Rui; Vilaprinyo, Ester; Sorribas, Albert; Solsona, Francesc; Farré, Gemma; Berman, Judit; Zorrilla, Uxue; Capell, Teresa; Sandmann, Gerhard; Zhu, Changfu; Christou, Paul; Alves, Rui

2016-09-01

Plant synthetic biology is still in its infancy. However, synthetic biology approaches have been used to manipulate and improve the nutritional and health value of staple food crops such as rice, potato and maize. With current technologies, production yields of the synthetic nutrients are a result of trial and error, and systematic rational strategies to optimize those yields are still lacking. Here, we present a workflow that combines gene expression and quantitative metabolomics with mathematical modeling to identify strategies for increasing production yields of nutritionally important carotenoids in the seed endosperm synthesized through alternative biosynthetic pathways in synthetic lines of white maize, which is normally devoid of carotenoids. Quantitative metabolomics and gene expression data are used to create and fit parameters of mathematical models that are specific to four independent maize lines. Sensitivity analysis and simulation of each model is used to predict which gene activities should be further engineered in order to increase production yields for carotenoid accumulation in each line. Some of these predictions (e.g. increasing Zmlycb/Gllycb will increase accumulated β-carotenes) are valid across the four maize lines and consistent with experimental observations in other systems. Other predictions are line specific. The workflow is adaptable to any other biological system for which appropriate quantitative information is available. Furthermore, we validate some of the predictions using experimental data from additional synthetic maize lines for which no models were developed. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

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.

What Makes the Optimal Wound Healing Material? A Review of Current Science and Introduction of a Synthetic Nanofabricated Wound Care Scaffold.

PubMed

MacEwan, Matthew R; MacEwan, Sarah; Kovacs, Tamas R; Batts, Joel

2017-10-02

Wound matrix materials are used to improve the regeneration of dermal and epidermal layers in both acute and chronic wounds. Contemporary wound matrices are primarily composed of biologic materials such as processed xenogeneic and allogeneic tissues. Unfortunately, existing biologic wound matrices possess multiple limitations including poor longevity, durability, strength, and enzymatic resistance required for persistent support for new tissue formation. A fully-synthetic, resorbable electrospun material (Restrata Wound Matrix, Acera, St.Louis, Missouri ) that exhibits structural similarities to the native extracellular matrix offers a new approach to the treatment of acute and chronic wounds. This novel matrix is the first product to combine the advantages of synthetic construction (e.g. resistance to enzymatic degradation, excellent biocompatibility, strength/durability and controlled degradation) with the positive attributes of biologic materials (e.g. biomimetic architecture similar to human extracellular matrix (ECM), fibrous architecture optimized to support cellular migration and proliferation, engineered porosity to encourage tissue ingrowth and vascularization). These features allow RWM to achieve rapid and complete healing of full-thickness wounds that, in preclinical studies, is comparable to Integra Bilayer Wound Matrix (Integra LifeSciences, Plainsboro, New Jersey), a gold standard biologic material with diverse clinical indications in the wound care. Together, this review suggests that the RWM offers a unique fully-synthetic alternative to existing biologic matrices that is effective, widely available, easy to store, simple to apply and low cost.

Laparoscopic Repair of Inguinal Hernia with Biomimetic Matrix

PubMed Central

2012-01-01

Background and Objectives: Materials utilized for the repair of hernias fall into 2 broad categories, synthetics and biologics. Each has its merits and drawbacks. The synthetics have a permanent, inherent strength but are associated with some incidence of chronic pain. The biologics rely on variable tissue regeneration to give strength to the repair, limiting their use to specific situations. However, thanks to their transient presence and tissue ingrowth, the biologics do not result in a significant incidence of chronic pain. We studied the use of a biomimetic (REVIVE, Biomerix Corporation, Fremont, CA) in this setting in an attempt to obviate the disadvantages of each material. Methods: Fourteen patients underwent laparoscopic repair by totally extraperitoneal and transabdominal preperitoneal techniques of 16 inguinal hernias. Follow-up was as long as 19 mo, and 8 patients were followed for > 12 mo. There were no recurrences and a 5% incidence of functionally insignificant discomfort. Results: REVIVE is shown in histology and in vivo to demonstrate regeneration and tissue ingrowth into the polycarbonate/polyuria matrix similar to that in the biologics rather than scarring or encapsulation. There were no recurrences, indicating its strength and resilience as a permanent repair similar to that in the synthetics. Conclusion: This is proof of the concept that a biomimetic may bridge the gap between the biologics and synthetics and may be able to be utilized on a regular basis with the benefits of both materials and without their drawbacks. PMID:23484565

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

Improved Genome Assembly and Annotation for the Rock Pigeon (Columba livia)

PubMed Central

Holt, Carson; Campbell, Michael; Keays, David A.; Edelman, Nathaniel; Kapusta, Aurélie; Maclary, Emily; T. Domyan, Eric; Suh, Alexander; Warren, Wesley C.; Yandell, Mark; Gilbert, M. Thomas P.; Shapiro, Michael D.

2018-01-01

The domestic rock pigeon (Columba livia) is among the most widely distributed and phenotypically diverse avian species. C. livia is broadly studied in ecology, genetics, physiology, behavior, and evolutionary biology, and has recently emerged as a model for understanding the molecular basis of anatomical diversity, the magnetic sense, and other key aspects of avian biology. Here we report an update to the C. livia genome reference assembly and gene annotation dataset. Greatly increased scaffold lengths in the updated reference assembly, along with an updated annotation set, provide improved tools for evolutionary and functional genetic studies of the pigeon, and for comparative avian genomics in general. PMID:29519939

Synthetic Biology: Life, Jim, but Not As We Know It

NASA Astrophysics Data System (ADS)

Hallinan, Jennifer

Frankenstein, Mary Shelley's classic tale of horror, warns of the perils of hubris: of the terrible fate that awaits when Man plays God and attempts to create life. Molecular biologists are clearly not listening. Not content with merely inserting the occasional gene into the genome of an existing organism. they are developing a whole new field, Synthetic Biology, which aims to engineer from first principles organisms with desirable, controllable qualities.

Financial implications of ventral hernia repair: a hospital cost analysis.

PubMed

Reynolds, Drew; Davenport, Daniel L; Korosec, Ryan L; Roth, J Scott

2013-01-01

Complicated ventral hernias are often referred to tertiary care centers. Hospital costs associated with these repairs include direct costs (mesh materials, supplies, and nonsurgeon labor costs) and indirect costs (facility fees, equipment depreciation, and unallocated labor). Operative supplies represent a significant component of direct costs, especially in an era of proprietary synthetic meshes and biologic grafts. We aim to evaluate the cost-effectiveness of complex abdominal wall hernia repair at a tertiary care referral facility. Cost data on all consecutive open ventral hernia repairs (CPT codes 49560, 49561, 49565, and 49566) performed between 1 July 2008 and 31 May 2011 were analyzed. Cases were analyzed based upon hospital status (inpatient vs. outpatient) and whether the hernia repair was a primary or secondary procedure. We examined median net revenue, direct costs, contribution margin, indirect costs, and net profit/loss. Among primary hernia repairs, cost data were further analyzed based upon mesh utilization (no mesh, synthetic, or biologic). Four-hundred and fifteen patients underwent ventral hernia repair (353 inpatients and 62 outpatients); 173 inpatients underwent ventral hernia repair as the primary procedure; 180 inpatients underwent hernia repair as a secondary procedure. Median net revenue ($17,310 vs. 10,360, p < 0.001) and net losses (3,430 vs. 1,700, p < 0.025) were significantly greater for those who underwent hernia repair as a secondary procedure. Among inpatients undergoing ventral hernia repair as the primary procedure, 46 were repaired without mesh; 79 were repaired with synthetic mesh and 48 with biologic mesh. Median direct costs for cases performed without mesh were $5,432; median direct costs for those using synthetic and biologic mesh were $7,590 and 16,970, respectively (p < .01). Median net losses for repairs without mesh were $500. Median net profit of $60 was observed for synthetic mesh-based repairs. The median contribution margin for cases utilizing biologic mesh was -$4,560, and the median net financial loss was $8,370. Outpatient ventral hernia repairs, with and without synthetic mesh, resulted in median net losses of $1,560 and 230, respectively. Ventral hernia repair is associated with overall financial losses. Inpatient synthetic mesh repairs are essentially budget neutral. Outpatient and inpatient repairs without mesh result in net financial losses. Inpatient biologic mesh repairs result in a negative contribution margin and striking net financial losses. Cost-effective strategies for managing ventral hernias in a tertiary care environment need to be developed in light of the financial implications of this patient population.

Standards for plant synthetic biology: a common syntax for exchange of DNA parts.

PubMed

Patron, Nicola J; Orzaez, Diego; Marillonnet, Sylvestre; Warzecha, Heribert; Matthewman, Colette; Youles, Mark; Raitskin, Oleg; Leveau, Aymeric; Farré, Gemma; Rogers, Christian; Smith, Alison; Hibberd, Julian; Webb, Alex A R; Locke, James; Schornack, Sebastian; Ajioka, Jim; Baulcombe, David C; Zipfel, Cyril; Kamoun, Sophien; Jones, Jonathan D G; Kuhn, Hannah; Robatzek, Silke; Van Esse, H Peter; Sanders, Dale; Oldroyd, Giles; Martin, Cathie; Field, Rob; O'Connor, Sarah; Fox, Samantha; Wulff, Brande; Miller, Ben; Breakspear, Andy; Radhakrishnan, Guru; Delaux, Pierre-Marc; Loqué, Dominique; Granell, Antonio; Tissier, Alain; Shih, Patrick; Brutnell, Thomas P; Quick, W Paul; Rischer, Heiko; Fraser, Paul D; Aharoni, Asaph; Raines, Christine; South, Paul F; Ané, Jean-Michel; Hamberger, Björn R; Langdale, Jane; Stougaard, Jens; Bouwmeester, Harro; Udvardi, Michael; Murray, James A H; Ntoukakis, Vardis; Schäfer, Patrick; Denby, Katherine; Edwards, Keith J; Osbourn, Anne; Haseloff, Jim

2015-10-01

Inventors in the field of mechanical and electronic engineering can access multitudes of components and, thanks to standardization, parts from different manufacturers can be used in combination with each other. The introduction of BioBrick standards for the assembly of characterized DNA sequences was a landmark in microbial engineering, shaping the field of synthetic biology. Here, we describe a standard for Type IIS restriction endonuclease-mediated assembly, defining a common syntax of 12 fusion sites to enable the facile assembly of eukaryotic transcriptional units. This standard has been developed and agreed by representatives and leaders of the international plant science and synthetic biology communities, including inventors, developers and adopters of Type IIS cloning methods. Our vision is of an extensive catalogue of standardized, characterized DNA parts that will accelerate plant bioengineering. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Effect of chemical and biological surfactants on activated sludge of MBR system: microscopic analysis and foam test.

PubMed

Capodici, Marco; Di Bella, Gaetano; Nicosia, Salvatore; Torregrossa, Michele

2015-02-01

A bench-scale MBR unit was operated, under stressing condition, with the aim of stimulating the onset of foaming in the activated sludge. Possible synergies between synthetic surfactants in the wastewater and biological surfactants (Extra-Cellular Polymeric Substances, EPSs) were investigated by changing C/N ratio. The growth of filamentous bacteria was also discussed. The MBR unit provided satisfactory overall carbon removal overall efficiencies: in particular, synthetic surfactants were removed with efficiency higher than 90% and 95% for non-ionic and ionic surfactants, respectively. Lab investigation suggested also the importance to reduce synthetic surfactants presence entering into mixed liquor: otherwise, their presence can significantly worsen the natural foaming caused by biological surfactants (EPSs) produced by bacteria. Finally, a new analytic method based on "ink test" has been proposed as a useful tool to achieve a valuation of EPSs bound fraction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthetic Biology Toolbox for Controlling Gene Expression in the Cyanobacterium Synechococcus sp. strain PCC 7002

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

Markley, Andrew L.; Begemann, Matthew B.; Clarke, Ryan E.

The application of synthetic biology requires characterized tools to precisely control gene expression. This toolbox of genetic parts previously did not exist for the industrially promising cyanobacterium, Synechococcus sp. strain PCC 7002. To address this gap, two orthogonal constitutive promoter libraries, one based on a cyanobacterial promoter and the other ported from Escherichia coli, were built and tested in PCC 7002. The libraries demonstrated 3 and 2.5 log dynamic ranges, respectively, but correlated poorly with E. coli expression levels. These promoter libraries were then combined to create and optimize a series of IPTG inducible cassettes. The resultant induction system hadmore » a 48-fold dynamic range and was shown to out-perform P trc constructs. Finally, a RBS library was designed and tested in PCC 7002. The presented synthetic biology toolbox will enable accelerated engineering of PCC 7002.« less

Synthetic Biology Toolbox for Controlling Gene Expression in the Cyanobacterium Synechococcus sp. strain PCC 7002

DOE PAGES

Markley, Andrew L.; Begemann, Matthew B.; Clarke, Ryan E.; ...

2014-09-12

The application of synthetic biology requires characterized tools to precisely control gene expression. This toolbox of genetic parts previously did not exist for the industrially promising cyanobacterium, Synechococcus sp. strain PCC 7002. To address this gap, two orthogonal constitutive promoter libraries, one based on a cyanobacterial promoter and the other ported from Escherichia coli, were built and tested in PCC 7002. The libraries demonstrated 3 and 2.5 log dynamic ranges, respectively, but correlated poorly with E. coli expression levels. These promoter libraries were then combined to create and optimize a series of IPTG inducible cassettes. The resultant induction system hadmore » a 48-fold dynamic range and was shown to out-perform P trc constructs. Finally, a RBS library was designed and tested in PCC 7002. The presented synthetic biology toolbox will enable accelerated engineering of PCC 7002.« less

Spatially organizing biochemistry: choosing a strategy to translate synthetic biology to the factory.

PubMed

Jakobson, Christopher M; Tullman-Ercek, Danielle; Mangan, Niall M

2018-05-29

Natural biochemical systems are ubiquitously organized both in space and time. Engineering the spatial organization of biochemistry has emerged as a key theme of synthetic biology, with numerous technologies promising improved biosynthetic pathway performance. One strategy, however, may produce disparate results for different biosynthetic pathways. We use a spatially resolved kinetic model to explore this fundamental design choice in systems and synthetic biology. We predict that two example biosynthetic pathways have distinct optimal organization strategies that vary based on pathway-dependent and cell-extrinsic factors. Moreover, we demonstrate that the optimal design varies as a function of kinetic and biophysical properties, as well as culture conditions. Our results suggest that organizing biosynthesis has the potential to substantially improve performance, but that choosing the appropriate strategy is key. The flexible design-space analysis we propose can be adapted to diverse biosynthetic pathways, and lays a foundation to rationally choose organization strategies for biosynthesis.

Modular design of synthetic gene circuits with biological parts and pools.

PubMed

Marchisio, Mario Andrea

2015-01-01

Synthetic gene circuits can be designed in an electronic fashion by displaying their basic components-Standard Biological Parts and Pools of molecules-on the computer screen and connecting them with hypothetical wires. This procedure, achieved by our add-on for the software ProMoT, was successfully applied to bacterial circuits. Recently, we have extended this design-methodology to eukaryotic cells. Here, highly complex components such as promoters and Pools of mRNA contain hundreds of species and reactions whose calculation demands a rule-based modeling approach. We showed how to build such complex modules via the joint employment of the software BioNetGen (rule-based modeling) and ProMoT (modularization). In this chapter, we illustrate how to utilize our computational tool for synthetic biology with the in silico implementation of a simple eukaryotic gene circuit that performs the logic AND operation.

Organic synthesis: the art and science of replicating the molecules of living nature and creating others like them in the laboratory.

PubMed

Nicolaou, K C

2014-03-08

Synthetic organic chemists have the power to replicate some of the most intriguing molecules of living nature in the laboratory and apply their developed synthetic strategies and technologies to construct variations of them. Such molecules facilitate biology and medicine, as they often find uses as biological tools and drug candidates for clinical development. In addition, by employing sophisticated catalytic reactions and appropriately designed synthetic processes, they can synthesize not only the molecules of nature and their analogues, but also myriad other organic molecules for potential applications in many areas of science, technology and everyday life. After a short historical introduction, this article focuses on recent advances in the field of organic synthesis with demonstrative examples of total synthesis of complex bioactive molecules, natural or designed, from the author's laboratories, and their impact on chemistry, biology and medicine.

The Role of Synthetic Biology in the Design of Microbial Cell Factories for Biofuel Production

PubMed Central

Colin, Verónica Leticia; Rodríguez, Analía; Cristóbal, Héctor Antonio

2011-01-01

Insecurity in the supply of fossil fuels, volatile fuel prices, and major concerns regarding climate change have sparked renewed interest in the production of fuels from renewable resources. Because of this, the use of biodiesel has grown dramatically during the last few years and is expected to increase even further in the future. Biodiesel production through the use of microbial systems has marked a turning point in the field of biofuels since it is emerging as an attractive alternative to conventional technology. Recent progress in synthetic biology has accelerated the ability to analyze, construct, and/or redesign microbial metabolic pathways with unprecedented precision, in order to permit biofuel production that is amenable to industrial applications. The review presented here focuses specifically on the role of synthetic biology in the design of microbial cell factories for efficient production of biodiesel. PMID:22028591

BioPartsDB: a synthetic biology workflow web-application for education and research.

PubMed

Stracquadanio, Giovanni; Yang, Kun; Boeke, Jef D; Bader, Joel S

2016-11-15

Synthetic biology has become a widely used technology, and expanding applications in research, education and industry require progress tracking for team-based DNA synthesis projects. Although some vendors are beginning to supply multi-kilobase sequence-verified constructs, synthesis workflows starting with short oligos remain important for cost savings and pedagogical benefit. We developed BioPartsDB as an open source, extendable workflow management system for synthetic biology projects with entry points for oligos and larger DNA constructs and ending with sequence-verified clones. BioPartsDB is released under the MIT license and available for download at https://github.com/baderzone/biopartsdb Additional documentation and video tutorials are available at https://github.com/baderzone/biopartsdb/wiki An Amazon Web Services image is available from the AWS Market Place (ami-a01d07c8). joel.bader@jhu.edu. © The Author 2016. Published by Oxford University Press.

[Progress in synthetic biology of pinocembrin].

PubMed

Guo, Lei; Kong, Jianqiang

2015-04-01

Pinocembrin, belonging to flavanons, was isolated from various plants. Pinocembrin has a variety of pharmacological activities, such as neuroprotective effect, antimicrobial activity, and antioxidant efficacy. Pinocembrin was approved as class I drugs to its phase II clinical trial by CFDA in 2009, mainly used for the treatment of ischemic stroke. As a promising compound, the manufacturing technologies of pinocembrin, including chemical synthesis, extraction from plant and synthetic biology, have attracted many attentions. Compared with the first two technologies, synthetic biology has many advantages, such as environment-friendly and low-cost. Construction of biosynthetic pathway in microorganism offers promising results for large scale pinocembrin production by fermentation after taking lots of effective strategies. This article reviews some of recent strategies in microorganisms to improve the yield, with focus on the selection of appropriate the key enzyme sources, the supply of precursors and cofactors by microorganisms, the choice of substance and the level of the key enzyme expression.

Foundations and Emerging Paradigms for Computing in Living Cells.

PubMed

Ma, Kevin C; Perli, Samuel D; Lu, Timothy K

2016-02-27

Genetic circuits, composed of complex networks of interacting molecular machines, enable living systems to sense their dynamic environments, perform computation on the inputs, and formulate appropriate outputs. By rewiring and expanding these circuits with novel parts and modules, synthetic biologists have adapted living systems into vibrant substrates for engineering. Diverse paradigms have emerged for designing, modeling, constructing, and characterizing such artificial genetic systems. In this paper, we first provide an overview of recent advances in the development of genetic parts and highlight key engineering approaches. We then review the assembly of these parts into synthetic circuits from the perspectives of digital and analog logic, systems biology, and metabolic engineering, three areas of particular theoretical and practical interest. Finally, we discuss notable challenges that the field of synthetic biology still faces in achieving reliable and predictable forward-engineering of artificial biological circuits. Copyright © 2016. Published by Elsevier Ltd.

Organic synthesis: the art and science of replicating the molecules of living nature and creating others like them in the laboratory

PubMed Central

Nicolaou, K. C.

2014-01-01

Synthetic organic chemists have the power to replicate some of the most intriguing molecules of living nature in the laboratory and apply their developed synthetic strategies and technologies to construct variations of them. Such molecules facilitate biology and medicine, as they often find uses as biological tools and drug candidates for clinical development. In addition, by employing sophisticated catalytic reactions and appropriately designed synthetic processes, they can synthesize not only the molecules of nature and their analogues, but also myriad other organic molecules for potential applications in many areas of science, technology and everyday life. After a short historical introduction, this article focuses on recent advances in the field of organic synthesis with demonstrative examples of total synthesis of complex bioactive molecules, natural or designed, from the author’s laboratories, and their impact on chemistry, biology and medicine. PMID:24611027

Abdominal wall reinforcement: biologic vs. degradable synthetic devices.

PubMed

Gruber-Blum, S; Brand, J; Keibl, C; Fortelny, R H; Redl, H; Mayer, F; Petter-Puchner, A H

2017-04-01

New biodegradable synthetic and biologic hernia implants have been promoted for rapid integration and tissue reinforcement in challenging repairs, e.g. at the hiatus or in contaminated wound fields. Interestingly, experimental data to support or falsify this assumption is scarce. Synthetic (BioA ® ) and biologic implants (porcine and bovine collagen matrices Strattice ® and Veritas ® ) have been tested in experimental onlay hernia repair in rats in observation periods of 30 and 60 days. The key outcome parameters were mesh integration and reinforcement of the tissue at the implant site over sutured and sealed defects as well as comparison to native abdominal wall. Macroscopic assessment, biomechanical analysis and histology with haematoxylin/eosin staining, collagen staining and van Willebrand factor staining for detection of neovascularization were performed. BioA ® was well integrated. Although the matrices were already fragmented at 60 days follow-up, hernia sites treated with synthetic scaffolds showed a significantly enhanced tissue deflection and resistance to burst force when compared to the native abdominal wall. In porcine and bovine matrices, tissue integration and shrinkage were significantly inferior to BioA ® . Histology revealed a lack of fibroblast ingrowth through mesh interstices in biologic samples, whereas BioA ® was tightly connected to the underlying tissue by reticular collagen fibres. Strattice ® and Veritas ® yielded reduced tissue integration and significant shrinkage, prohibiting further biomechanical tests. The synthetic BioA ® provides little inherent strength but reticular collagen remodelling led to an augmentation of the scar due to significantly higher burst force resistance in comparison to native tissue.

FMM: a web server for metabolic pathway reconstruction and comparative analysis.

PubMed

Chou, Chih-Hung; Chang, Wen-Chi; Chiu, Chih-Min; Huang, Chih-Chang; Huang, Hsien-Da

2009-07-01

Synthetic Biology, a multidisciplinary field, is growing rapidly. Improving the understanding of biological systems through mimicry and producing bio-orthogonal systems with new functions are two complementary pursuits in this field. A web server called FMM (From Metabolite to Metabolite) was developed for this purpose. FMM can reconstruct metabolic pathways form one metabolite to another metabolite among different species, based mainly on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and other integrated biological databases. Novel presentation for connecting different KEGG maps is newly provided. Both local and global graphical views of the metabolic pathways are designed. FMM has many applications in Synthetic Biology and Metabolic Engineering. For example, the reconstruction of metabolic pathways to produce valuable metabolites or secondary metabolites in bacteria or yeast is a promising strategy for drug production. FMM provides a highly effective way to elucidate the genes from which species should be cloned into those microorganisms based on FMM pathway comparative analysis. Consequently, FMM is an effective tool for applications in synthetic biology to produce both drugs and biofuels. This novel and innovative resource is now freely available at http://FMM.mbc.nctu.edu.tw/.

pClone: Synthetic Biology Tool Makes Promoter Research Accessible to Beginning Biology Students

PubMed Central

Eckdahl, Todd; Cronk, Brian; Andresen, Corinne; Frederick, Paul; Huckuntod, Samantha; Shinneman, Claire; Wacker, Annie; Yuan, Jason

2014-01-01

The Vision and Change report recommended genuine research experiences for undergraduate biology students. Authentic research improves science education, increases the number of scientifically literate citizens, and encourages students to pursue research. Synthetic biology is well suited for undergraduate research and is a growing area of science. We developed a laboratory module called pClone that empowers students to use advances in molecular cloning methods to discover new promoters for use by synthetic biologists. Our educational goals are consistent with Vision and Change and emphasize core concepts and competencies. pClone is a family of three plasmids that students use to clone a new transcriptional promoter or mutate a canonical promoter and measure promoter activity in Escherichia coli. We also developed the Registry of Functional Promoters, an open-access database of student promoter research results. Using pre- and posttests, we measured significant learning gains among students using pClone in introductory biology and genetics classes. Student posttest scores were significantly better than scores of students who did not use pClone. pClone is an easy and affordable mechanism for large-enrollment labs to meet the high standards of Vision and Change. PMID:26086659

JP-8 and Other Military Fuels (2014 UPDATE)

DTIC Science & Technology

2014-06-17

Biodiesel , Ethanol – Not cost competitive with fossil fuels • 2nd Generation Alternative Fuels – Fischer-Tropsch Synthetic Paraffinic Kerosene (FT-SPK) and...Generation Alternative Fuels Unclassified • Biodiesel – a fuel comprised of mono-alkyl esters of long chain fatty acids derived from Vegetable oils or

What is the evidence for the use of biologic or biosynthetic meshes in abdominal wall reconstruction?

PubMed

Köckerling, F; Alam, N N; Antoniou, S A; Daniels, I R; Famiglietti, F; Fortelny, R H; Heiss, M M; Kallinowski, F; Kyle-Leinhase, I; Mayer, F; Miserez, M; Montgomery, A; Morales-Conde, S; Muysoms, F; Narang, S K; Petter-Puchner, A; Reinpold, W; Scheuerlein, H; Smietanski, M; Stechemesser, B; Strey, C; Woeste, G; Smart, N J

2018-04-01

Although many surgeons have adopted the use of biologic and biosynthetic meshes in complex abdominal wall hernia repair, others have questioned the use of these products. Criticism is addressed in several review articles on the poor standard of studies reporting on the use of biologic meshes for different abdominal wall repairs. The aim of this consensus review is to conduct an evidence-based analysis of the efficacy of biologic and biosynthetic meshes in predefined clinical situations. A European working group, "BioMesh Study Group", composed of invited surgeons with a special interest in surgical meshes, formulated key questions, and forwarded them for processing in subgroups. In January 2016, a workshop was held in Berlin where the findings were presented, discussed, and voted on for consensus. Findings were set out in writing by the subgroups followed by consensus being reached. For the review, 114 studies and background analyses were used. The cumulative data regarding biologic mesh under contaminated conditions do not support the claim that it is better than synthetic mesh. Biologic mesh use should be avoided when bridging is needed. In inguinal hernia repair biologic and biosynthetic meshes do not have a clear advantage over the synthetic meshes. For prevention of incisional or parastomal hernias, there is no evidence to support the use of biologic/biosynthetic meshes. In complex abdominal wall hernia repairs (incarcerated hernia, parastomal hernia, infected mesh, open abdomen, enterocutaneous fistula, and component separation technique), biologic and biosynthetic meshes do not provide a superior alternative to synthetic meshes. The routine use of biologic and biosynthetic meshes cannot be recommended.

Status of the NASA GMAO Observing System Simulation Experiment

NASA Technical Reports Server (NTRS)

Prive, Nikki C.; Errico, Ronald M.

2014-01-01

An Observing System Simulation Experiment (OSSE) is a pure modeling study used when actual observations are too expensive or difficult to obtain. OSSEs are valuable tools for determining the potential impact of new observing systems on numerical weather forecasts and for evaluation of data assimilation systems (DAS). An OSSE has been developed at the NASA Global Modeling and Assimilation Office (GMAO, Errico et al 2013). The GMAO OSSE uses a 13-month integration of the European Centre for Medium- Range Weather Forecasts 2005 operational model at T511/L91 resolution for the Nature Run (NR). Synthetic observations have been updated so that they are based on real observations during the summer of 2013. The emulated observation types include AMSU-A, MHS, IASI, AIRS, and HIRS4 radiance data, GPS-RO, and conventional types including aircraft, rawinsonde, profiler, surface, and satellite winds. The synthetic satellite wind observations are colocated with the NR cloud fields, and the rawinsondes are advected during ascent using the NR wind fields. Data counts for the synthetic observations are matched as closely as possible to real data counts, as shown in Figure 2. Errors are added to the synthetic observations to emulate representativeness and instrument errors. The synthetic errors are calibrated so that the statistics of observation innovation and analysis increments in the OSSE are similar to the same statistics for assimilation of real observations, in an iterative method described by Errico et al (2013). The standard deviations of observation minus forecast (xo-H(xb)) are compared for the OSSE and real data in Figure 3. The synthetic errors include both random, uncorrelated errors, and an additional correlated error component for some observational types. Vertically correlated errors are included for conventional sounding data and GPS-RO, and channel correlated errors are introduced to AIRS and IASI (Figure 4). HIRS, AMSU-A, and MHS have a component of horizontally correlated error. The forecast model used by the GMAO OSSE is the Goddard Earth Observing System Model, Version 5 (GEOS-5) with Gridpoint Statistical Interpolation (GSI) DAS. The model version has been updated to v. 5.13.3, corresponding to the current operational model. Forecasts are run on a cube-sphere grid with 180 points along each edge of the cube (approximately 0.5 degree horizontal resolution) with 72 vertical levels. The DAS is cycled at 6-hour intervals, with 240 hour forecasts launched daily at 0000 UTC. Evaluation of the forecasting skill for July and August is currently underway. Prior versions of the GMAO OSSE have been found to have greater forecasting skill than real world forecasts. It is anticipated that similar forecast skill will be found in the updated OSSE.

Teens and Steroids: A Dangerous Combo

MedlinePlus

... Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products For Consumers Home For Consumers Consumer Updates Teens and Steroids: ... as it is surprising. Nov. 4, 2013 Related Consumer Updates Beware of Fraudulent Dietary Supplements More in ...

SB6.0: The 6th International meeting on Synthetic Biology, July 9-11, 2013

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

Kahl, Linda J.

The Synthetic Biology conference series (SBx.0) is the preeminent academic meeting in synthetic biology. Organized by the BioBricks Foundation, the SBx.0 conference series brings together leading researchers, students, industry executives, and policy makers from around the world to share, consider, debate, and plan efforts to make biology easier to engineer. Historically held every two years, the SBx.0 conferences are held in alternating locations in the United States, Europe, and Asia to encourage global participation and collaboration so that the ramifications of synthetic biology research and development are most likely to be safe ethical, and beneficial. On 9-11 July 2013, themore » 6th installment of the synthetic biology conference series (SB6.0) was held on the campus of Imperial College London (http://sb6.biobricks.org). The SB6.0 conference was attended by over 700 people, and many more were able to participate via video digital conference (http://sb6.biobricks.org/digital-conference/). Over the course of three days, the SB6.0 conference agenda included plenary sessions, workshops, and poster presentations covering topics ranging from the infrastructure needs arising when “Systematic Engineering Meets Biological Complexity” and design-led considerations for “Connecting People and Technologies” to discussions on “Engineering Biology for New Materials,” “Assessing Risk and Managing Biocontainment,” and “New Directions for Energy and Sustainability.” The $10,150 grant awarded by the U.S. Department of Energy (DE-SC0010233) to the BioBricks Foundation was used to provide partial reimbursement for the travel expenses of leading researchers from the United States to speak at the SB6.0 conference. A total of $9,450 was used to reimburse U.S. speakers for actual expenses related to the SB6.0 conference, including airfare (economy or coach only), ground transportation, hotel, and registration fees. In addition, $700 of the grant was used to offset direct administrative costs associated with selecting speakers (preparing announcements, evaluating abstract submissions) and handling travel arrangements. Leading U.S. researchers selected to speak at the SB6.0 conference included: Adam Arkin, Ph.D. Division Director of the Physical Biosciences Division at the Lawrence Berkeley National Laboratory and Professor in the Department of Bioengineering at UC Berkeley Jay Keasling, Ph.D. Professor in the Department of Bioengineering at Berkeley, Senior Faculty Scientist and Associate Laboratory Director of the Lawrence Berkeley National Laboratory, and Chief Executive Officer of the Joint BioEnergy Institute. Debra Mathews, Ph.D. Assistant Director for Science Programs for the Johns Hopkins Berman Institute of Bioethics, Assistant Professor in the Department of Pediatrics, and Affiliate Faculty in the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine. Richard Murray, Ph.D. Thomas E. and Doris Everhart Professor of Control & Dynamical Systems and Bioengineering at Caltech. Sarah Richardson, Ph.D. Distinguished Postdoctoral Fellow in Genomics at the Lawrence Berkeley National Laboratory and the Department of Energy Joint Genome Institute. and others (for a complete listing of speakers presenting at the SB6.0 conference see http://sb6.biobricks.org/speakers/) The SB6.0 conference was the largest synthetic biology conference to date, and highlights of the SB6.0 conference have been published in a special issue of ACS Synthetic Biology (http://pubs.acs.org/toc/asbcd6/3/3). The BioBricks Foundation appreciates the support of the U.S. Department of Energy in helping to make this most influential and important conference in the field of synthetic biology a success.« less

Engineering Ecosystems and Synthetic Ecologies#

PubMed Central

Mee, Michael T; Wang, Harris H

2012-01-01

Microbial ecosystems play an important role in nature. Engineering these systems for industrial, medical, or biotechnological purposes are important pursuits for synthetic biologists and biological engineers moving forward. Here, we provide a review of recent progress in engineering natural and synthetic microbial ecosystems. We highlight important forward engineering design principles, theoretical and quantitative models, new experimental and manipulation tools, and possible applications of microbial ecosystem engineering. We argue that simply engineering individual microbes will lead to fragile homogenous populations that are difficult to sustain, especially in highly heterogeneous and unpredictable environments. Instead, engineered microbial ecosystems are likely to be more robust and able to achieve complex tasks at the spatial and temporal resolution needed for truly programmable biology. PMID:22722235

Microbial Extremophiles for Earth and Beyond: Pushing the Boundaries with Synthetic Biology

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2017-01-01

All organisms live in a multi-dimensional physical and chemical niche space. Discoveries in the 20th century enormously expanded the range of what was considered "habitable." However, the current diversity of life on Earth begs the question of what terrestrial life - or indeed, another life form - would be capable of. With the needs of both modern laboratory science and the burgeoning field of biotechnology, as well as our deeply held desire to answer the question "are we alone in the universe?, we are exploiting the tools of synthetic biology to probe the question of whether we can create "synthetic extremophiles" or, as our lab has dubbed them, "Hell Cells."

XFEM-based modeling of successive resections for preoperative image updating

NASA Astrophysics Data System (ADS)

Vigneron, Lara M.; Robe, Pierre A.; Warfield, Simon K.; Verly, Jacques G.

2006-03-01

We present a new method for modeling organ deformations due to successive resections. We use a biomechanical model of the organ, compute its volume-displacement solution based on the eXtended Finite Element Method (XFEM). The key feature of XFEM is that material discontinuities induced by every new resection can be handled without remeshing or mesh adaptation, as would be required by the conventional Finite Element Method (FEM). We focus on the application of preoperative image updating for image-guided surgery. Proof-of-concept demonstrations are shown for synthetic and real data in the context of neurosurgery.

Synthetic cannabinoids 2015: An update for pediatricians in clinical practice

PubMed Central

Castellanos, Daniel; Gralnik, Leonard M

2016-01-01

Synthetic cannabinoids are a group of substances in the world of designer drugs that have become increasingly popular over the past few years. Synthetic cannabinoids are a chemically diverse group of compounds functionally similar to THC. Since first appearing on the world market a few years ago these compounds have evolved rapidly. Newer more potent analogues have been developed. Identifying youth who abuse these substances can be difficult. Newer forms of consumption have also evolved. These products are now manufactured in products that look like natural cannabis resin and in liquid cartridges used in electronic cigarettes. Synthetic cannabinoids appear to be associated with potentially dangerous health effects that are more severe than that of marijuana. Some synthetic cannabinoid compounds have been associated with serious physical consequences, such as, seizures, myocardial infarction and renal damage. In addition, psychoactive effects, such as aggression, confusion, anxiety and psychosis have also been reported. The diagnosis remains primarily clinical with toxicological confirmation difficult due to manufacturers constantly developing new analogues to avoid detection. Pediatricians are urged to familiarize themselves with these drugs and the typical presentations of patients who use them. PMID:26862498

Toward scalable parts families for predictable design of biological circuits.

PubMed

Lucks, Julius B; Qi, Lei; Whitaker, Weston R; Arkin, Adam P

2008-12-01

Our current ability to engineer biological circuits is hindered by design cycles that are costly in terms of time and money, with constructs failing to operate as desired, or evolving away from the desired function once deployed. Synthetic biologists seek to understand biological design principles and use them to create technologies that increase the efficiency of the genetic engineering design cycle. Central to the approach is the creation of biological parts--encapsulated functions that can be composited together to create new pathways with predictable behaviors. We define five desirable characteristics of biological parts--independence, reliability, tunability, orthogonality and composability, and review studies of small natural and synthetic biological circuits that provide insights into each of these characteristics. We propose that the creation of appropriate sets of families of parts with these properties is a prerequisite for efficient, predictable engineering of new function in cells and will enable a large increase in the sophistication of genetic engineering applications.

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

Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Synthetic Biology Research Program, National University of Singapore, Singapore

Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fattymore » acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes.« less

An integrated cell-free metabolic platform for protein production and synthetic biology

PubMed Central

Jewett, Michael C; Calhoun, Kara A; Voloshin, Alexei; Wuu, Jessica J; Swartz, James R

2008-01-01

Cell-free systems offer a unique platform for expanding the capabilities of natural biological systems for useful purposes, i.e. synthetic biology. They reduce complexity, remove structural barriers, and do not require the maintenance of cell viability. Cell-free systems, however, have been limited by their inability to co-activate multiple biochemical networks in a single integrated platform. Here, we report the assessment of biochemical reactions in an Escherichia coli cell-free platform designed to activate natural metabolism, the Cytomim system. We reveal that central catabolism, oxidative phosphorylation, and protein synthesis can be co-activated in a single reaction system. Never before have these complex systems been shown to be simultaneously activated without living cells. The Cytomim system therefore promises to provide the metabolic foundation for diverse ab initio cell-free synthetic biology projects. In addition, we describe an improved Cytomim system with enhanced protein synthesis yields (up to 1200 mg/l in 2 h) and lower costs to facilitate production of protein therapeutics and biochemicals that are difficult to make in vivo because of their toxicity, complexity, or unusual cofactor requirements. PMID:18854819

A synthetic biological quantum optical system

DOE PAGES

Lishchuk, Anna; Kodali, Goutham; Mancini, Joshua A.; ...

2018-01-01

Strong coupling between plasmon modes and chlorins in synthetic light-harvesting maquette proteins yields hybrid light–matter states (plexcitons) whose energies are controlled by design of protein structure, enabling the creation of new states not seen under weak coupling.

Design, synthesis, and biological activity of second-generation synthetic oleanane triterpenoids.

PubMed

Fu, Liangfeng; Lin, Qi-Xian; Onyango, Evans O; Liby, Karen T; Sporn, Michael B; Gribble, Gordon W

2017-07-19

We report the synthesis and biological activity of C-24 demethyl CDDO-Me 2 and the C-28 amide derivatives 3 and 4, which are analogues of the anti-inflammatory synthetic triterpenoid bardoxolone methyl (CDDO-Me) 1. Demethylation of the C-24 methyl group was accomplished via "abnormal Beckmann" rearrangement and subsequent ring A reformation. Amides 3 and 4 were found to be potent inhibitors of the production of the inflammatory mediator NO in vitro.

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.

Light Activated Cell Migration in Synthetic Extracellular Matrices

PubMed Central

Guo, Qiongyu; Wang, Xiaobo; Tibbitt, Mark W.; Anseth, Kristi S.; Montell, Denise J.; Elisseeff, Jennifer H.

2012-01-01

Synthetic extracellular matrices provide a framework in which cells can be exposed to defined physical and biological cues. However no method exists to manipulate single cells within these matrices. It is desirable to develop such methods in order to understand fundamental principles of cell migration and define conditions that support or inhibit cell movement within these matrices. Here, we present a strategy for manipulating individual mammalian stem cells in defined synthetic hydrogels through selective optical activation of Rac, which is an intracellular signaling protein that plays a key role in cell migration. Photoactivated cell migration in synthetic hydrogels depended on mechanical and biological cues in the biomaterial. Real-time hydrogel photodegradation was employed to create geometrically defined channels and spaces in which cells could be photoactivated to migrate. Cell migration speed was significantly higher in the photo-etched channels and cells could easily change direction of movement compared to the bulk hydrogels. PMID:22889487

HHS guidance on synthetic DNA is the right step.

PubMed

Gronvall, Gigi Kwik

2010-12-01

Synthetic biology has advanced to the point where some pathogens can be manufactured from scratch. This technical leap has beneficent implications for medical research and vaccine design, but it also raises concerns that the technology could be used to produce a deadly pathogen for nefarious use. Addressing these concerns, the Department of Health and Human Services (HHS) released their Screening Framework Guidance for Providers of Synthetic Double-Stranded DNA on October 13, 2010. They took the right approach: The oversight framework for gene synthesis companies included in this guidance is adaptable to new technical developments and changing risks, it can be implemented immediately, it can be readily adopted by other countries, and it will cost little. Though there have been some calls to increase the regulatory controls on synthetic biology, these should be resisted. For now, at least, the oversight is appropriate to the risks.

Gene expression platform for synthetic biology in the human pathogen Streptococcus pneumoniae.

PubMed

Sorg, Robin A; Kuipers, Oscar P; Veening, Jan-Willem

2015-03-20

The human pathogen Streptococcus pneumoniae (pneumococcus) is a bacterium that owes its success to complex gene expression regulation patterns on both the cellular and the population level. Expression of virulence factors enables a mostly hazard-free presence of the commensal, in balance with the host and niche competitors. Under specific circumstances, changes in this expression can result in a more aggressive behavior and the reversion to the invasive form as pathogen. These triggering conditions are very difficult to study due to the fact that environmental cues are often unknown or barely possible to simulate outside the host (in vitro). An alternative way of investigating expression patterns is found in synthetic biology approaches of reconstructing regulatory networks that mimic an observed behavior with orthogonal components. Here, we created a genetic platform suitable for synthetic biology approaches in S. pneumoniae and characterized a set of standardized promoters and reporters. We show that our system allows for fast and easy cloning with the BglBrick system and that reliable and robust gene expression after integration into the S. pneumoniae genome is achieved. In addition, the cloning system was extended to allow for direct linker-based assembly of ribosome binding sites, peptide tags, and fusion proteins, and we called this new generally applicable standard "BglFusion". The gene expression platform and the methods described in this study pave the way for employing synthetic biology approaches in S. pneumoniae.

Steps towards the synthetic biology of polyketide biosynthesis.

PubMed

Cummings, Matthew; Breitling, Rainer; Takano, Eriko

2014-02-01

Nature is providing a bountiful pool of valuable secondary metabolites, many of which possess therapeutic properties. However, the discovery of new bioactive secondary metabolites is slowing down, at a time when the rise of multidrug-resistant pathogens and the realization of acute and long-term side effects of widely used drugs lead to an urgent need for new therapeutic agents. Approaches such as synthetic biology are promising to deliver a much-needed boost to secondary metabolite drug development through plug-and-play optimized hosts and refactoring novel or cryptic bacterial gene clusters. Here, we discuss this prospect focusing on one comprehensively studied class of clinically relevant bioactive molecules, the polyketides. Extensive efforts towards optimization and derivatization of compounds via combinatorial biosynthesis and classical engineering have elucidated the modularity, flexibility and promiscuity of polyketide biosynthetic enzymes. Hence, a synthetic biology approach can build upon a solid basis of guidelines and principles, while providing a new perspective towards the discovery and generation of novel and new-to-nature compounds. We discuss the lessons learned from the classical engineering of polyketide synthases and indicate their importance when attempting to engineer biosynthetic pathways using synthetic biology approaches for the introduction of novelty and overexpression of products in a controllable manner. © 2013 The Authors FEMS Microbiology Letters published by John Wiley & Sons Ltd on behalf of Federation of European Microbiological Societies.

Synthetic biology approaches to fluorinated polyketides

PubMed Central

Thuronyi, Benjamin W.; Chang, Michelle C. Y.

2016-01-01

Conspectus The catalytic diversity of living systems offers a broad range of opportunities for developing new methods to produce small molecule targets such as fuels, materials, and pharmaceuticals. In addition to providing cost-effective and renewable methods for large-scale commercial processes, the exploration of the unusual chemical phenotypes found in living organisms can also enable the expansion of chemical space for discovery of novel function by combining orthogonal attributes from both synthetic and biological chemistry. In this context, we have focused on the development of new fluorine chemistry using synthetic biology approaches. While fluorine has become an important feature in compounds of synthetic origin, the scope of biological fluorine chemistry in living systems is limited, with fewer than 20 organofluorine natural products identified to date. In order to expand the diversity of biosynthetically accessible organofluorines, we have begun to develop methods for the site-selective introduction of fluorine into complex natural products by engineering biosynthetic machinery to incorporate fluorinated building blocks. To gain insight into how both enzyme active sites and metabolic pathways can be evolved to manage and select for fluorinated compounds, we have studied one of the only characterized natural hosts for organofluorine biosynthesis, the soil microbe Streptomyces cattleya. This information provides a template for designing engineered organofluorine enzymes, pathways, and hosts and has allowed us to initiate construction of enzymatic and cellular pathways for the production of fluorinated polyketides. PMID:25719427

Achieving biopolymer synergy in systems chemistry.

PubMed

Bai, Yushi; Chotera, Agata; Taran, Olga; Liang, Chen; Ashkenasy, Gonen; Lynn, David G

2018-05-31

Synthetic and materials chemistry initiatives have enabled the translation of the macromolecular functions of biology into synthetic frameworks. These explorations into alternative chemistries of life attempt to capture the versatile functionality and adaptability of biopolymers in new orthogonal scaffolds. Information storage and transfer, however, so beautifully represented in the central dogma of biology, require multiple components functioning synergistically. Over a single decade, the emerging field of systems chemistry has begun to catalyze the construction of mutualistic biopolymer networks, and this review begins with the foundational small-molecule-based dynamic chemical networks and peptide amyloid-based dynamic physical networks on which this effort builds. The approach both contextualizes the versatile approaches that have been developed to enrich chemical information in synthetic networks and highlights the properties of amyloids as potential alternative genetic elements. The successful integration of both chemical and physical networks through β-sheet assisted replication processes further informs the synergistic potential of these networks. Inspired by the cooperative synergies of nucleic acids and proteins in biology, synthetic nucleic-acid-peptide chimeras are now being explored to extend their informational content. With our growing range of synthetic capabilities, structural analyses, and simulation technologies, this foundation is radically extending the structural space that might cross the Darwinian threshold for the origins of life as well as creating an array of alternative systems capable of achieving the progressive growth of novel informational materials.