Advanced genetic tools enable synthetic biology in the oleaginous microalgae Nannochloropsis sp.

PubMed

Poliner, Eric; Farré, Eva M; Benning, Christoph

2018-03-06

Nannochloropsis is a genus of fast-growing microalgae that are regularly used for biotechnology applications. Nannochloropsis species have a high triacylglycerol content and their polar lipids are rich in the omega-3 long-chain polyunsaturated fatty acid, eicosapentaenoic acid. Placed in the heterokont lineage, the Nannochloropsis genus has a complex evolutionary history. Genome sequences are available for several species, and a number of transcriptomic datasets have been produced, making this genus a facile model for comparative genomics. There is a growing interest in Nannochloropsis species as models for the study of microalga lipid metabolism and as a chassis for synthetic biology. Recently, techniques for gene stacking, and targeted gene disruption and repression in the Nannochloropsis genus have been developed. These tools enable gene-specific, mechanistic studies and have already allowed the engineering of improved Nannochloropsis strains with superior growth, or greater bioproduction.

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.

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

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.

Synthetic biology meets bioprinting: enabling technologies for humans on Mars (and Earth).

PubMed

Rothschild, Lynn J

2016-08-15

Human exploration off planet is severely limited by the cost of launching materials into space and by re-supply. Thus materials brought from Earth must be light, stable and reliable at destination. Using traditional approaches, a lunar or Mars base would require either transporting a hefty store of metals or heavy manufacturing equipment and construction materials for in situ extraction; both would severely limit any other mission objectives. Long-term human space presence requires periodic replenishment, adding a massive cost overhead. Even robotic missions often sacrifice science goals for heavy radiation and thermal protection. Biology has the potential to solve these problems because life can replicate and repair itself, and perform a wide variety of chemical reactions including making food, fuel and materials. Synthetic biology enhances and expands life's evolved repertoire. Using organisms as feedstock, additive manufacturing through bioprinting will make possible the dream of producing bespoke tools, food, smart fabrics and even replacement organs on demand. This new approach and the resulting novel products will enable human exploration and settlement on Mars, while providing new manufacturing approaches for life on Earth. © 2016 The Author(s).

Synthetic biology meets bioprinting: enabling technologies for humans on Mars (and Earth)

PubMed Central

Rothschild, Lynn J.

2016-01-01

Human exploration off planet is severely limited by the cost of launching materials into space and by re-supply. Thus materials brought from Earth must be light, stable and reliable at destination. Using traditional approaches, a lunar or Mars base would require either transporting a hefty store of metals or heavy manufacturing equipment and construction materials for in situ extraction; both would severely limit any other mission objectives. Long-term human space presence requires periodic replenishment, adding a massive cost overhead. Even robotic missions often sacrifice science goals for heavy radiation and thermal protection. Biology has the potential to solve these problems because life can replicate and repair itself, and perform a wide variety of chemical reactions including making food, fuel and materials. Synthetic biology enhances and expands life's evolved repertoire. Using organisms as feedstock, additive manufacturing through bioprinting will make possible the dream of producing bespoke tools, food, smart fabrics and even replacement organs on demand. This new approach and the resulting novel products will enable human exploration and settlement on Mars, while providing new manufacturing approaches for life on Earth. PMID:27528764

Toxicological Implications of Released Particulate Matter during Thermal Decomposition of Nano-Enabled Thermoplastics

PubMed Central

Watson-Wright, Christa; Singh, Dilpreet; Demokritou, Philip

2017-01-01

Nano-enabled thermoplastics are part of the growing market of nano-enabled products (NEPs) that have vast utility in several industries and consumer goods. The use and disposal of NEPs at their end of life has raised concerns about the potential release of constituent engineered nanomaterials (ENMs) during thermal decomposition and their impact on environmental health and safety. To investigate this issue, industrially relevant nano-enabled thermoplastics including polyurethane, polycarbonate, and polypropylene containing carbon nanotubes (0.1 and 3% w/v, respectively), polyethylene containing nanoscale iron oxide (5% w/v), and ethylene vinyl acetate containing nanoscale titania (2 and 5% w/v) along with their pure thermoplastic matrices were thermally decomposed using the recently developed lab based Integrated Exposure Generation System (INEXS). The life cycle released particulate matter (called LCPM) was monitored using real time instrumentation, size fractionated, sampled, extracted and prepared for toxicological analysis using primary small airway epithelial cells to assess potential toxicological effects. Various cellular assays were used to assess reactive oxygen species and total glutathione as measurements of oxidative stress along with mitochondrial function, cellular viability, and DNA damage. By comparing toxicological profiles of LCPM released from polymer only (control) with nano-enabled LCPM, potential nanofiller effects due to the use of ENMs were determined. We observed associations between NEP properties such as the percent nanofiller loading, host matrix, and nanofiller chemical composition and the physico-chemical properties of released LCPM, which were linked to biological outcomes. More specifically, an increase in percent nanofiller loading promoted a toxicological response independent of increasing LCPM dose. Importantly, differences in host matrix and nanofiller composition were shown to enhance biological activity and toxicity of LCPM

Toxicological Implications of Released Particulate Matter during Thermal Decomposition of Nano-Enabled Thermoplastics.

PubMed

Watson-Wright, Christa; Singh, Dilpreet; Demokritou, Philip

2017-01-01

Nano-enabled thermoplastics are part of the growing market of nano-enabled products (NEPs) that have vast utility in several industries and consumer goods. The use and disposal of NEPs at their end of life has raised concerns about the potential release of constituent engineered nanomaterials (ENMs) during thermal decomposition and their impact on environmental health and safety. To investigate this issue, industrially relevant nano-enabled thermoplastics including polyurethane, polycarbonate, and polypropylene containing carbon nanotubes (0.1 and 3% w/v, respectively), polyethylene containing nanoscale iron oxide (5% w/v), and ethylene vinyl acetate containing nanoscale titania (2 and 5% w/v) along with their pure thermoplastic matrices were thermally decomposed using the recently developed lab based Integrated Exposure Generation System (INEXS). The life cycle released particulate matter (called LCPM) was monitored using real time instrumentation, size fractionated, sampled, extracted and prepared for toxicological analysis using primary small airway epithelial cells to assess potential toxicological effects. Various cellular assays were used to assess reactive oxygen species and total glutathione as measurements of oxidative stress along with mitochondrial function, cellular viability, and DNA damage. By comparing toxicological profiles of LCPM released from polymer only (control) with nano-enabled LCPM, potential nanofiller effects due to the use of ENMs were determined. We observed associations between NEP properties such as the percent nanofiller loading, host matrix, and nanofiller chemical composition and the physico-chemical properties of released LCPM, which were linked to biological outcomes. More specifically, an increase in percent nanofiller loading promoted a toxicological response independent of increasing LCPM dose. Importantly, differences in host matrix and nanofiller composition were shown to enhance biological activity and toxicity of LCPM

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

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

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

Towards a whole-cell modeling approach for synthetic biology

NASA Astrophysics Data System (ADS)

Purcell, Oliver; Jain, Bonny; Karr, Jonathan R.; Covert, Markus W.; Lu, Timothy K.

2013-06-01

Despite rapid advances over the last decade, synthetic biology lacks the predictive tools needed to enable rational design. Unlike established engineering disciplines, the engineering of synthetic gene circuits still relies heavily on experimental trial-and-error, a time-consuming and inefficient process that slows down the biological design cycle. This reliance on experimental tuning is because current modeling approaches are unable to make reliable predictions about the in vivo behavior of synthetic circuits. A major reason for this lack of predictability is that current models view circuits in isolation, ignoring the vast number of complex cellular processes that impinge on the dynamics of the synthetic circuit and vice versa. To address this problem, we present a modeling approach for the design of synthetic circuits in the context of cellular networks. Using the recently published whole-cell model of Mycoplasma genitalium, we examined the effect of adding genes into the host genome. We also investigated how codon usage correlates with gene expression and find agreement with existing experimental results. Finally, we successfully implemented a synthetic Goodwin oscillator in the whole-cell model. We provide an updated software framework for the whole-cell model that lays the foundation for the integration of whole-cell models with synthetic gene circuit models. This software framework is made freely available to the community to enable future extensions. We envision that this approach will be critical to transforming the field of synthetic biology into a rational and predictive engineering discipline.

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.

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.

Nano-imaging enabled via self-assembly

PubMed Central

McLeod, Euan; Ozcan, Aydogan

2014-01-01

SUMMARY Imaging object details with length scales below approximately 200 nm has been historically difficult for conventional microscope objective lenses because of their inability to resolve features smaller than one-half the optical wavelength. Here we review some of the recent approaches to surpass this limit by harnessing self-assembly as a fabrication mechanism. Self-assembly can be used to form individual nano- and micro-lenses, as well as to form extended arrays of such lenses. These lenses have been shown to enable imaging with resolutions as small as 50 nm half-pitch using visible light, which is well below the Abbe diffraction limit. Furthermore, self-assembled nano-lenses can be used to boost contrast and signal levels from small nano-particles, enabling them to be detected relative to background noise. Finally, alternative nano-imaging applications of self-assembly are discussed, including three-dimensional imaging, enhanced coupling from light-emitting diodes, and the fabrication of contrast agents such as quantum dots and nanoparticles. PMID:25506387

[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.

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.

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.

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.

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.

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 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

The PLOS ONE Synthetic Biology Collection: Six Years and Counting

PubMed Central

Peccoud, Jean; Isalan, Mark

2012-01-01

Since it was launched in 2006, PLOS ONE has published over fifty articles illustrating the many facets of the emerging field of synthetic biology. This article reviews these publications by organizing them into broad categories focused on DNA synthesis and assembly techniques, the development of libraries of biological parts, the use of synthetic biology in protein engineering applications, and the engineering of gene regulatory networks and metabolic pathways. Finally, we review articles that describe enabling technologies such as software and modeling, along with new instrumentation. In order to increase the visibility of this body of work, the papers have been assembled into the PLOS ONE Synthetic Biology Collection (www.ploscollections.org/synbio). Many of the innovative features of the PLOS ONE web site will help make this collection a resource that will support a lively dialogue between readers and authors of PLOS ONE synthetic biology papers. The content of the collection will be updated periodically by including relevant articles as they are published by the journal. Thus, we hope that this collection will continue to meet the publishing needs of the synthetic biology community. PMID:22916228

The PLOS ONE synthetic biology collection: six years and counting.

PubMed

Peccoud, Jean; Isalan, Mark

2012-01-01

Since it was launched in 2006, PLOS ONE has published over fifty articles illustrating the many facets of the emerging field of synthetic biology. This article reviews these publications by organizing them into broad categories focused on DNA synthesis and assembly techniques, the development of libraries of biological parts, the use of synthetic biology in protein engineering applications, and the engineering of gene regulatory networks and metabolic pathways. Finally, we review articles that describe enabling technologies such as software and modeling, along with new instrumentation. In order to increase the visibility of this body of work, the papers have been assembled into the PLOS ONE Synthetic Biology Collection (www.ploscollections.org/synbio). Many of the innovative features of the PLOS ONE web site will help make this collection a resource that will support a lively dialogue between readers and authors of PLOS ONE synthetic biology papers. The content of the collection will be updated periodically by including relevant articles as they are published by the journal. Thus, we hope that this collection will continue to meet the publishing needs of the synthetic biology community.

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.

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.

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.

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.

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: 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.

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.

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

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 Synthetic Biology Open Language (SBOL) provides a community standard for communicating designs in synthetic biology.

PubMed

Galdzicki, Michal; Clancy, Kevin P; Oberortner, Ernst; Pocock, Matthew; Quinn, Jacqueline Y; Rodriguez, Cesar A; Roehner, Nicholas; Wilson, Mandy L; Adam, Laura; Anderson, J Christopher; Bartley, Bryan A; Beal, Jacob; Chandran, Deepak; Chen, Joanna; Densmore, Douglas; Endy, Drew; Grünberg, Raik; Hallinan, Jennifer; Hillson, Nathan J; Johnson, Jeffrey D; Kuchinsky, Allan; Lux, Matthew; Misirli, Goksel; Peccoud, Jean; Plahar, Hector A; Sirin, Evren; Stan, Guy-Bart; Villalobos, Alan; Wipat, Anil; Gennari, John H; Myers, Chris J; Sauro, Herbert M

2014-06-01

The re-use of previously validated designs is critical to the evolution of synthetic biology from a research discipline to an engineering practice. Here we describe the Synthetic Biology Open Language (SBOL), a proposed data standard for exchanging designs within the synthetic biology community. SBOL represents synthetic biology designs in a community-driven, formalized format for exchange between software tools, research groups and commercial service providers. The SBOL Developers Group has implemented SBOL as an XML/RDF serialization and provides software libraries and specification documentation to help developers implement SBOL in their own software. We describe early successes, including a demonstration of the utility of SBOL for information exchange between several different software tools and repositories from both academic and industrial partners. As a community-driven standard, SBOL will be updated as synthetic biology evolves to provide specific capabilities for different aspects of the synthetic biology workflow.

[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.

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.

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 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: 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

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: 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.

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

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 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

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.

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.

US Competitiveness in Synthetic Biology

PubMed Central

2015-01-01

Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative—additional investments will expand markets—but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized. PMID:26690379

US Competitiveness in Synthetic Biology.

PubMed

Gronvall, Gigi Kwik

2015-01-01

Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative--additional investments will expand markets--but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized.

Peculiarities of hydration of Portland cement with synthetic nano-silica

NASA Astrophysics Data System (ADS)

Kotsay, Galyna

2017-12-01

Application of nano-materials in cement products significantly, improves their properties. Of course, the effectiveness of the materials depends on their quantity and the way they are introduced into the system. So far, amongst nano-materials used in construction, the most preferred was nano-silica. This research investigated the effect of synthetic precipitated nano-silica on the cement hydration as well as, on the physical and mechanical properties of pastes and mortars. Obtained results showed that admixture of nano-silica enhanced flexural and compressive strength of cement after 2 and 28 days, however, only when admixture made up 0.5% and 1.0%. On the other hand, the use of nano-silica in the amount 2% had some limitations, due to its ability to agglomerate, which resulted in deterioration of the rheological and mechanical properties.

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.

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.

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 ).

Space Synthetic Biology Project

NASA Technical Reports Server (NTRS)

Howard, David; Roman, Monsi; Mansell, James (Matt)

2015-01-01

Synthetic biology is an effort to make genetic engineering more useful by standardizing sections of genetic code. By standardizing genetic components, biological engineering will become much more similar to traditional fields of engineering, in which well-defined components and subsystems are readily available in markets. Specifications of the behavior of those components and subsystems can be used to model a system which incorporates them. Then, the behavior of the novel system can be simulated and optimized. Finally, the components and subsystems can be purchased and assembled to create the optimized system, which most often will exhibit behavior similar to that indicated by the model. The Space Synthetic Biology project began in 2012 as a multi-Center effort. The purpose of this project was to harness Synthetic Biology principals to enable NASA's missions. A central target for application was to Environmental Control & Life Support (ECLS). Engineers from NASA Marshall Space Flight Center's (MSFC's) ECLS Systems Development Branch (ES62) were brought into the project to contribute expertise in operational ECLS systems. Project lead scientists chose to pursue the development of bioelectrochemical technologies to spacecraft life support. Therefore, the ECLS element of the project became essentially an effort to develop a bioelectrochemical ECLS subsystem. Bioelectrochemical systems exploit the ability of many microorganisms to drive their metabolisms by direct or indirect utilization of electrical potential gradients. Whereas many microorganisms are capable of deriving the energy required for the processes of interest (such as carbon dioxide (CO2) fixation) from sunlight, it is believed that subsystems utilizing electrotrophs will exhibit smaller mass, volume, and power requirements than those that derive their energy from sunlight. In the first 2 years of the project, MSFC personnel conducted modeling, simulation, and conceptual design efforts to assist the

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.

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.

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

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.

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: 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

Synthetic Nanoelectronic Probes for Biological Cells and Tissue

PubMed Central

2013-01-01

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

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.

Micro/nano-fabrication technologies for cell biology.

PubMed

Qian, Tongcheng; Wang, Yingxiao

2010-10-01

Micro/nano-fabrication techniques, such as soft lithography and electrospinning, have been well-developed and widely applied in many research fields in the past decade. Due to the low costs and simple procedures, these techniques have become important and popular for biological studies. In this review, we focus on the studies integrating micro/nano-fabrication work to elucidate the molecular mechanism of signaling transduction in cell biology. We first describe different micro/nano-fabrication technologies, including techniques generating three-dimensional scaffolds for tissue engineering. We then introduce the application of these technologies in manipulating the physical or chemical micro/nano-environment to regulate the cellular behavior and response, such as cell life and death, differentiation, proliferation, and cell migration. Recent advancement in integrating the micro/nano-technologies and live cell imaging are also discussed. Finally, potential schemes in cell biology involving micro/nano-fabrication technologies are proposed to provide perspectives on the future research activities.

Micro/nano-fabrication technologies for cell biology

PubMed Central

Qian, Tongcheng

2012-01-01

Micro/nano-fabrication techniques, such as soft lithography and electrospinning, have been well-developed and widely applied in many research fields in the past decade. Due to the low costs and simple procedures, these techniques have become important and popular for biological studies. In this review, we focus on the studies integrating micro/nano-fabrication work to elucidate the molecular mechanism of signaling transduction in cell biology. We first describe different micro/nano-fabrication technologies, including techniques generating three-dimensional scaffolds for tissue engineering. We then introduce the application of these technologies in manipulating the physical or chemical micro/nano-environment to regulate the cellular behavior and response, such as cell life and death, differentiation, proliferation, and cell migration. Recent advancement in integrating the micro/nano-technologies and live cell imaging are also discussed. Finally, potential schemes in cell biology involving micro/nano-fabrication technologies are proposed to provide perspectives on the future research activities. PMID:20490938

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."

VisBOL: Web-Based Tools for Synthetic Biology Design Visualization.

PubMed

McLaughlin, James Alastair; Pocock, Matthew; Mısırlı, Göksel; Madsen, Curtis; Wipat, Anil

2016-08-19

VisBOL is a Web-based application that allows the rendering of genetic circuit designs, enabling synthetic biologists to visually convey designs in SBOL visual format. VisBOL designs can be exported to formats including PNG and SVG images to be embedded in Web pages, presentations and publications. The VisBOL tool enables the automated generation of visualizations from designs specified using the Synthetic Biology Open Language (SBOL) version 2.0, as well as a range of well-known bioinformatics formats including GenBank and Pigeoncad notation. VisBOL is provided both as a user accessible Web site and as an open-source (BSD) JavaScript library that can be used to embed diagrams within other content and software.

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.

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.

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 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."

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.

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

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.

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.

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.

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 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.

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.

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.

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…

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.

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.

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.

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

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.

Nano-enabled drug delivery: a research profile.

PubMed

Zhou, Xiao; Porter, Alan L; Robinson, Douglas K R; Shim, Min Suk; Guo, Ying

2014-07-01

Nano-enabled drug delivery (NEDD) systems are rapidly emerging as a key area for nanotechnology application. Understanding the status and developmental prospects of this area around the world is important to determine research priorities, and to evaluate and direct progress. Global research publication and patent databases provide a reservoir of information that can be tapped to provide intelligence for such needs. Here, we present a process to allow for extraction of NEDD-related information from these databases by involving topical experts. This process incorporates in-depth analysis of NEDD literature review papers to identify key subsystems and major topics. We then use these to structure global analysis of NEDD research topical trends and collaborative patterns, inform future innovation directions. This paper describes the process of how to derive nano-enabled drug delivery-related information from global research and patent databases in an effort to perform comprehensive global analysis of research trends and directions, along with collaborative patterns. Copyright © 2014 Elsevier Inc. All rights reserved.

Demonstration of a Nano-Enabled Space Power System

NASA Technical Reports Server (NTRS)

Raffaelle, Ryne; Hunter, Roger C.; Baker, Christopher

2017-01-01

The Nano-Enabled Space Power System will demonstrate power systems with nanomaterial-enhanced components as are placement for CubeSat power generation, transmission, and storage. Successful flights of these nano-power systems will accelerate the use of this revolutionary technology in the aerospace industry. The use of nano materials in solar cells, wire harnesses,and lithium ion batteries can increase the device performance without significantly altering the devices physical dimensions or the devices operating range (temperature,voltage, current). In many cases, the use of nanomaterials widens the viable range of operating conditions, such as increased depth of discharge of lithium ion batteries, tunable bandgaps in solar cells, and increased flexure tolerance of wire harnesses.

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.

Risks to health care workers from nano-enabled medical products.

PubMed

Murashov, Vladimir; Howard, John

2015-01-01

Nanotechnology is rapidly expanding into the health care industry. However, occupational safety and health risks of nano-enabled medical products have not been thoroughly assessed. This manuscript highlights occupational risk mitigation practices for nano-enabled medical products throughout their life cycle for all major workplace settings including (1) medical research laboratories, (2) pharmaceutical manufacturing facilities, (3) clinical dispensing pharmacies, (4) health care delivery facilities, (5) home health care, (6) health care support, and (7) medical waste management. It further identifies critical research needs for ensuring worker protection in the health care industry.

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.

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

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 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

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.

Mammalian Synthetic Biology: Time for Big MACs.

PubMed

Martella, Andrea; Pollard, Steven M; Dai, Junbiao; Cai, Yizhi

2016-10-21

The enabling technologies of synthetic biology are opening up new opportunities for engineering and enhancement of mammalian cells. This will stimulate diverse applications in many life science sectors such as regenerative medicine, development of biosensing cell lines, therapeutic protein production, and generation of new synthetic genetic regulatory circuits. Harnessing the full potential of these new engineering-based approaches requires the design and assembly of large DNA constructs-potentially up to chromosome scale-and the effective delivery of these large DNA payloads to the host cell. Random integration of large transgenes, encoding therapeutic proteins or genetic circuits into host chromosomes, has several drawbacks such as risks of insertional mutagenesis, lack of control over transgene copy-number and position-specific effects; these can compromise the intended functioning of genetic circuits. The development of a system orthogonal to the endogenous genome is therefore beneficial. Mammalian artificial chromosomes (MACs) are functional, add-on chromosomal elements, which behave as normal chromosomes-being replicating and portioned to daughter cells at each cell division. They are deployed as useful gene expression vectors as they remain independent from the host genome. MACs are maintained as a single-copy and can accommodate multiple gene expression cassettes of, in theory, unlimited DNA size (MACs up to 10 megabases have been constructed). MACs therefore enabled control over ectopic gene expression and represent an excellent platform to rapidly prototype and characterize novel synthetic gene circuits without recourse to engineering the host genome. This review describes the obstacles synthetic biologists face when working with mammalian systems and how the development of improved MACs can overcome these-particularly given the spectacular advances in DNA synthesis and assembly that are fuelling this research area.

[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.

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 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.

[Progress in synthetic biology of "973 Funding Program" in China].

PubMed

Chen, Guoqiang; Wang, Ying

2015-06-01

This paper reviews progresses made in China from 2011 in areas of "Synthetic Biology" supported by State Basic Research 973 Program. Till the end of 2014, 9 "synthetic biology" projects have been initiated with emphasis on "microbial manufactures" with the 973 Funding Program. Combined with the very recent launch of one project on "mammalian cell synthetic biology" and another on "plant synthetic biology", Chinese "synthetic biology" research reflects its focus on "manufactures" while not giving up efforts on "synthetic biology" of complex systems.

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).

Nanobiotechnology: synthetic biology meets materials science.

PubMed

Jewett, Michael C; Patolsky, Fernando

2013-08-01

Nanotechnology, the area of science focused on the control of matter in the nanometer scale, allows ground-breaking changes of the fundamental properties of matter that are often radically different compared to those exhibited by the bulk counterparts. In view of the fact that dimensionality plays a key role in determining the qualities of matter, the realization of the great potential of nanotechnology has opened the door to other disciplines such as life sciences and medicine, where the merging between them offers exciting new applications, along with basic science research. The application of nanotechnology in life sciences, nanobiotechnology, is now having a profound impact on biological circuit design, bioproduction systems, synthetic biology, medical diagnostics, disease therapy and drug delivery. This special issue is dedicated to the overview of how we are learning to control biopolymers and biological machines at the molecular- and nanoscale. In addition, it covers far-reaching progress in the design and synthesis of nanoscale materials, thus enabling the construction of integrated systems in which the component blocks are comparable in size to the chemical and biological entities under investigation. Copyright © 2013 Elsevier Ltd. 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.

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

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).

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.

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.

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.

Recent advances in synthetic biology of cyanobacteria.

PubMed

Sengupta, Annesha; Pakrasi, Himadri B; Wangikar, Pramod P

2018-05-09

Cyanobacteria are attractive hosts that can be engineered for the photosynthetic production of fuels, fine chemicals, and proteins from CO 2 . Moreover, the responsiveness of these photoautotrophs towards different environmental signals, such as light, CO 2 , diurnal cycle, and metals make them potential hosts for the development of biosensors. However, engineering these hosts proves to be a challenging and lengthy process. Synthetic biology can make the process of biological engineering more predictable through the use of standardized biological parts that are well characterized and tools to assemble them. While significant progress has been made with model heterotrophic organisms, many of the parts and tools are not portable in cyanobacteria. Therefore, efforts are underway to develop and characterize parts derived from cyanobacteria. In this review, we discuss the reported parts and tools with the objective to develop cyanobacteria as cell factories or biosensors. We also discuss the issues related to characterization, tunability, portability, and the need to develop enabling technologies to engineer this "green" chassis.

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.

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.

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 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.

Nano-biosensors in cellular and molecular biology.

PubMed

Moradi, Sajad; Khaledian, Salar; Abdoli, Mohadese; Shahlaei, Mohsen; Kahrizi, Danial

2018-04-30

Detection and quantification of various biological and non-biological species today is one of the most important pillars of all experimental sciences, especially sciences related to human health. This may apply to a chemical in the factory wastewater or to identify a cancer cell in a person's body, it may be apply to trace a useful industrial microorganism or human or plant pathogenic microorganisms. In this regard, scientists from various sciences have always striven to design and provide tools and techniques for identifying and quantifying as accurately as possible to trace various analyte types with greater precision and specificity. Nano science, which has flourished in recent years and is nowadays widely used in all fields of science, also has a unique place in the design and manufacture of sensors and this, in addition to the new and special characteristics of nanoparticles, is due to the ability of nano-devices to penetrate into very tiny places to track the species. On the other hand, due to the high specificity of biological molecules in identifying and connecting to their receptors that have evolved over millions of years, Scientists are now trying to design hybrid devices using nano science and biology, called Nano-biosensors So that they can trace and quantify target molecules in very small amounts and in inaccessible places, such as within the organs and even the cells.

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.

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.

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).

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.

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.

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.

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.

[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.

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

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

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.

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.

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.

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).

Synthetic biology engineering of biofilms as nanomaterials factories.

PubMed

Nguyen, Peter Q

2017-06-15

Bottom-up fabrication of nanoscale materials has been a significant focus in materials science for expanding our technological frontiers. This assembly concept, however, is old news to biology - all living organisms fabricate themselves using bottom-up principles through a vast self-organizing system of incredibly complex biomolecules, a marvelous dynamic that we are still attempting to unravel. Can we use what we have gleaned from biology thus far to illuminate alternative strategies for designer nanomaterial manufacturing? In the present review article, new synthetic biology efforts toward using bacterial biofilms as platforms for the synthesis and secretion of programmable nanomaterials are described. Particular focus is given to self-assembling functional amyloids found in bacterial biofilms as re-engineerable modular nanomolecular components. Potential applications and existing challenges for this technology are also explored. This novel approach for repurposing biofilm systems will enable future technologies for using engineered living systems to grow artificial nanomaterials. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

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.

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

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.

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.

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

A Versatile Microfluidic Device for Automating Synthetic Biology.

PubMed

Shih, Steve C C; Goyal, Garima; Kim, Peter W; Koutsoubelis, Nicolas; Keasling, Jay D; Adams, Paul D; Hillson, Nathan J; Singh, Anup K

2015-10-16

New microbes are being engineered that contain the genetic circuitry, metabolic pathways, and other cellular functions required for a wide range of applications such as producing biofuels, biobased chemicals, and pharmaceuticals. Although currently available tools are useful in improving the synthetic biology process, further improvements in physical automation would help to lower the barrier of entry into this field. We present an innovative microfluidic platform for assembling DNA fragments with 10× lower volumes (compared to that of current microfluidic platforms) and with integrated region-specific temperature control and on-chip transformation. Integration of these steps minimizes the loss of reagents and products compared to that with conventional methods, which require multiple pipetting steps. For assembling DNA fragments, we implemented three commonly used DNA assembly protocols on our microfluidic device: Golden Gate assembly, Gibson assembly, and yeast assembly (i.e., TAR cloning, DNA Assembler). We demonstrate the utility of these methods by assembling two combinatorial libraries of 16 plasmids each. Each DNA plasmid is transformed into Escherichia coli or Saccharomyces cerevisiae using on-chip electroporation and further sequenced to verify the assembly. We anticipate that this platform will enable new research that can integrate this automated microfluidic platform to generate large combinatorial libraries of plasmids and will help to expedite the overall synthetic biology process.

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

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.

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

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

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 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.

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.

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.

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 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

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.

Macroporous nanowire nanoelectronic scaffolds for synthetic tissues

NASA Astrophysics Data System (ADS)

Tian, Bozhi; Liu, Jia; Dvir, Tal; Jin, Lihua; Tsui, Jonathan H.; Qing, Quan; Suo, Zhigang; Langer, Robert; Kohane, Daniel S.; Lieber, Charles M.

2012-11-01

The development of three-dimensional (3D) synthetic biomaterials as structural and bioactive scaffolds is central to fields ranging from cellular biophysics to regenerative medicine. As of yet, these scaffolds cannot electrically probe the physicochemical and biological microenvironments throughout their 3D and macroporous interior, although this capability could have a marked impact in both electronics and biomaterials. Here, we address this challenge using macroporous, flexible and free-standing nanowire nanoelectronic scaffolds (nanoES), and their hybrids with synthetic or natural biomaterials. 3D macroporous nanoES mimic the structure of natural tissue scaffolds, and they were formed by self-organization of coplanar reticular networks with built-in strain and by manipulation of 2D mesh matrices. NanoES exhibited robust electronic properties and have been used alone or combined with other biomaterials as biocompatible extracellular scaffolds for 3D culture of neurons, cardiomyocytes and smooth muscle cells. Furthermore, we show the integrated sensory capability of the nanoES by real-time monitoring of the local electrical activity within 3D nanoES/cardiomyocyte constructs, the response of 3D-nanoES-based neural and cardiac tissue models to drugs, and distinct pH changes inside and outside tubular vascular smooth muscle constructs.

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.

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.

Mimicking biological stress-strain behaviour with synthetic elastomers

NASA Astrophysics Data System (ADS)

Vatankhah-Varnosfaderani, Mohammad; Daniel, William F. M.; Everhart, Matthew H.; Pandya, Ashish A.; Liang, Heyi; Matyjaszewski, Krzysztof; Dobrynin, Andrey V.; Sheiko, Sergei S.

2017-09-01

Despite the versatility of synthetic chemistry, certain combinations of mechanical softness, strength, and toughness can be difficult to achieve in a single material. These combinations are, however, commonplace in biological tissues, and are therefore needed for applications such as medical implants, tissue engineering, soft robotics, and wearable electronics. Present materials synthesis strategies are predominantly Edisonian, involving the empirical mixing of assorted monomers, crosslinking schemes, and occluded swelling agents, but this approach yields limited property control. Here we present a general strategy for mimicking the mechanical behaviour of biological materials by precisely encoding their stress-strain curves in solvent-free brush- and comb-like polymer networks (elastomers). The code consists of three independent architectural parameters—network strand length, side-chain length and grafting density. Using prototypical poly(dimethylsiloxane) elastomers, we illustrate how this parametric triplet enables the replication of the strain-stiffening characteristics of jellyfish, lung, and arterial tissues.

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.

Biological effects of a nano red elemental selenium.

PubMed

Zhang, J S; Gao, X Y; Zhang, L D; Bao, Y P

2001-01-01

A novel selenium form, nano red elemental selenium (Nano-Se) was prepared by adding bovine serum albumin to the redox system of selenite and glutathione. Nano-Se has a 7-fold lower acute toxicity than sodium selenite in mice (LD(50) 113 and 15 mg Se/kg body weight respectively). In Se-deficient rat, both Nano-Se and selenite can increase tissue selenium and GPx activity. The biological activities of Nano-Se and selenite were compared in terms of cell proliferation, enzyme induction and protection against free racial-mediated damage in human hepatoma HepG2 cells. Nano-Se and selenite are similarly cell growth inhibited and stimulated synthesis of glutathione peroxidase (GPx), phospholipid hydroperoxide glutathione peroxidase (PHGPx) and thioredoxin reductase (TR). When HepG2 cells were co-treated with selenium and glutathione, Nano-Se showed less pro-oxidative effects than selenite, as measured by cell growth. These results demonstrate that Nano-Se has a similar bioavailability in the rat and antioxidant effects on cells.

An Implementation-Focused Bio/Algorithmic Workflow for Synthetic Biology.

PubMed

Goñi-Moreno, Angel; Carcajona, Marta; Kim, Juhyun; Martínez-García, Esteban; Amos, Martyn; de Lorenzo, Víctor

2016-10-21

As synthetic biology moves away from trial and error and embraces more formal processes, workflows have emerged that cover the roadmap from conceptualization of a genetic device to its construction and measurement. This latter aspect (i.e., characterization and measurement of synthetic genetic constructs) has received relatively little attention to date, but it is crucial for their outcome. An end-to-end use case for engineering a simple synthetic device is presented, which is supported by information standards and computational methods and focuses on such characterization/measurement. This workflow captures the main stages of genetic device design and description and offers standardized tools for both population-based measurement and single-cell analysis. To this end, three separate aspects are addressed. First, the specific vector features are discussed. Although device/circuit design has been successfully automated, important structural information is usually overlooked, as in the case of plasmid vectors. The use of the Standard European Vector Architecture (SEVA) is advocated for selecting the optimal carrier of a design and its thorough description in order to unequivocally correlate digital definitions and molecular devices. A digital version of this plasmid format was developed with the Synthetic Biology Open Language (SBOL) along with a software tool that allows users to embed genetic parts in vector cargoes. This enables annotation of a mathematical model of the device's kinetic reactions formatted with the Systems Biology Markup Language (SBML). From that point onward, the experimental results and their in silico counterparts proceed alongside, with constant feedback to preserve consistency between them. A second aspect involves a framework for the calibration of fluorescence-based measurements. One of the most challenging endeavors in standardization, metrology, is tackled by reinterpreting the experimental output in light of simulation results, allowing

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

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.

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

In vivo analysis of biocompatibility and vascularization of the synthetic bone grafting substitute NanoBone.

PubMed

Abshagen, K; Schrodi, I; Gerber, T; Vollmar, B

2009-11-01

One of the major challenges in the application of bone substitutes is adequate vascularization and biocompatibility of the implant. Thus, the temporal course of neovascularization and the microvascular inflammatory response of implants of NanoBone (fully synthetic nanocrystalline bone grafting material) were studied in vivo by using the mouse dorsal skinfold chamber model. Angiogenesis, microhemodynamics, and leukocyte-endothelial cell interaction were analyzed repetitively after implantation in the center and in the border zone of the implant up to 15 days. Both NanoBone granules and plates exhibited high biocompatibility comparable to that of cancellous bone, as indicated by a lack of venular leukocyte activation after implantation. In both synthetic NanoBone groups, signs of angiogenesis could be observed even at day 5 after implantation, whereas granules showed higher functional vessel density compared with NanoBone plates. The angiogenic response of the cancellous bone was markedly accelerated in the center of the implant tissue. Histologically, implant tissue showed an ingrowth of vascularized fibrous tissue into the material combined with an increased number of foreign-body giant cells. In conclusion, NanoBone, particularly in granular form, showed high biocompatibility and high angiogenic response, thus improving the healing of bone defects. Our results underline that, beside the composition and nanostructure, the macrostructure is also of importance for the incorporation of the biomaterial by the host tissue. (c) 2008 Wiley Periodicals, Inc.

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.

Ecological assessment of nano-enabled supercapacitors for automotive applications

NASA Astrophysics Data System (ADS)

Weil, M.; Dura, H.; Shimon, B.; Baumann, M.; Zimmermann, B.; Ziemann, S.; Lei, C.; Markoulidis, F.; Lekakou, T.; Decker, M.

2012-09-01

New materials on nano scale have the potential to overcome existing technical barriers and are one of the most promising key technologies to enable the decoupling of economic growth and resource consumption. Developing these innovative materials for industrial applications means facing a complex quality profile, which includes among others technical, economic, and ecological aspects. So far the two latter aspects are not sufficiently included in technology development, especially from a life cycle point of view. Supercapacitors are considered a promising option for electric energy storage in hybrid and full electric cars. In comparison with presently used lithium based electro chemical storage systems supercapacitors possess a high specific power, but a relatively low specific energy. Therefore, the goal of ongoing research is to develop a new generation of supercapacitors with high specific power and high specific energy. To reach this goal particularly nano materials are developed and tested on cell level. In the presented study the ecological implications (regarding known environmental effects) of carbon based nano materials are analysed using Life Cycle Assessment (LCA). Major attention is paid to efficiency gains of nano particle production due to scaling up of such processes from laboratory to industrial production scales. Furthermore, a developed approach will be displayed, how to assess the environmental impact of nano materials on an automotive system level over the whole life cycle.

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

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.

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.

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.

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.

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

Nano-enabled tribological thin film coatings: global patent scenario.

PubMed

Sivudu, Kurva S; Mahajan, Yashwant R; Joshi, Shrikant V

2014-01-01

The aim of this paper is to present current status and future prospects of nano-enabled tribological thin film coatings based on worldwide patent landscape analysis. The study also presents an overview of technological trends by carrying out state-of-the-art literature analysis, including survey of corporate websites. Nanostructured tribological coatings encompass a wide spectrum of nanoscale microstructures, including nanocrystalline, nanolayered, nano-multilayered, nanocomposite, nanogradient structures or their unique combinations, which are composed of single or multi-component phases. The distinct microstructural features of the coatings impart outstanding tribological properties combined with multifunctional attributes to the coated components. Their unique combination of remarkable properties make them ideal candidates for a wide range of applications in diverse fields such as cutting and metalworking tools, biomedical devices, automotive engine components, wear parts, hard disc drives etc. The patent landscape analysis has revealed that nano-enabled tribological thin film coatings have significant potential for commercial applications in view of the lion's share of corporate industry in patenting activity. The largest patent portfolio is held by Japan followed by USA, Germany, Sweden and China. The prominent players involved in this field are Mitsubishi Materials Corp., Sandvik Aktiebolag, Hitachi Ltd., Sumitomo Electric Industries Ltd., OC Oerlikon Corp., and so on. The outstanding potential of nanostructured thin film tribological coatings is yet to be fully unravelled and, therefore, immense opportunities are available in future for microstructurally engineered novel coatings to enhance their performance and functionality by many folds.

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.

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

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.

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.

Metabolic modelling in the development of cell factories by synthetic biology

PubMed Central

Jouhten, Paula

2012-01-01

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

Synthetic fossilization of soft biological tissues and their shape-preserving transformation into silica or electron-conductive replicas

DOE PAGES

Townson, Jason L.; Lin, Yu-Shen; Chou, Stanley S.; ...

2014-12-08

Structural preservation of complex biological systems from the subcellular to whole organism level in robust forms, enabling dissection and imaging while preserving 3D context, represents an enduring grand challenge in biology. Here we report a simple immersion method for structurally preserving intact organisms via conformal stabilization within silica. This self-limiting process, which we refer to as silica bioreplication, occurs by condensation of water-soluble silicic acid proximally to biomolecular interfaces throughout the organism. Conformal nanoscopic silicification of all biomolecular features imparts structural rigidity enabling the preservation of shape and nano-to-macroscale dimensional features upon drying to form a biocomposite and further highmore » temperature oxidative calcination to form silica replicas or reductive pyrolysis to form electrically conductive carbon replicas of complete organisms. Ultimately, the simplicity and generalizability of this approach should facilitate efforts in biological preservation and analysis and could enable the development of new classes of biomimetic composite materials.« less

[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.

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).

Fourier transform Raman spectroscopy of synthetic and biological calcium phosphates.

PubMed

Sauer, G R; Zunic, W B; Durig, J R; Wuthier, R E

1994-05-01

Fourier-transform (FT) Raman spectroscopy was used to characterize the organic and mineral components of biological and synthetic calcium phosphate minerals. Raman spectroscopy provides information on biological minerals that is complimentary to more widely used infrared methodologies as some infrared-inactive vibrational modes are Raman-active. The application of FT-Raman technology has, for the first time, enabled the problems of high sample fluorescence and low signal-to-noise that are inherent in calcified tissues to be overcome. Raman spectra of calcium phosphates are dominated by a very strong band near 960 cm-1 that arises from the symmetric stretching mode (v1) of the phosphate group. Other Raman-active phosphate vibrational bands are seen at approximately 1075 (v3), 590 (v4), and 435 cm-1 (v2). Minerals containing acidic phosphate groups show additional vibrational modes. The different calcium phosphate mineral phases can be distinguished from one another by the relative positions and shapes of these bands in the Raman spectra. FT-Raman spectra of nascent, nonmineralized matrix vesicles (MV) show a distinct absence of the phosphate v1 band even though these structures are rich in calcium and phosphate. Similar results were seen with milk casein and synthetic Ca-phosphatidyl-serine-PO4 complexes. Hence, the phosphate and/or acidic phosphate ions in these noncrystalline biological calcium phosphates is in a molecular environment that differs from that in synthetic amorphous calcium phosphate. In MV, the first distinct mineral phase to form contained acidic phosphate bands similar to those seen in octacalcium phosphate. The mineral phase present in fully mineralized MV was much more apatitic, resembling that found in bones and teeth.(ABSTRACT TRUNCATED AT 250 WORDS)

NanoSIMS for biological applications: Current practices and analyses

DOE PAGES

Nunez, Jamie R.; Renslow, Ryan S.; Cliff, III, John B.; ...

2017-09-27

Secondary ion mass spectrometry (SIMS) has become an increasingly utilized tool in biologically-relevant studies. Of these, high lateral resolution methodologies using the NanoSIMS 50/50L have been especially powerful within many biological fields over the past decade. Here, we provide a review of this technology, sample preparation and analysis considerations, examples of recent biological studies, data analysis, and current outlooks. Specifically, we offer an overview of SIMS and development of the NanoSIMS. We describe the major experimental factors that should be considered prior to NanoSIMS analysis and then provide information on best practices for data analysis and image generation, which includesmore » an in-depth discussion of appropriate colormaps. Additionally, we provide an open-source method for data representation that allows simultaneous visualization of secondary electron and ion information within a single image. Lastly, we present a perspective on the future of this technology and where we think it will have the greatest impact in near future.« less

NanoSIMS for biological applications: Current practices and analyses

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

Nunez, Jamie R.; Renslow, Ryan S.; Cliff, III, John B.

Secondary ion mass spectrometry (SIMS) has become an increasingly utilized tool in biologically-relevant studies. Of these, high lateral resolution methodologies using the NanoSIMS 50/50L have been especially powerful within many biological fields over the past decade. Here, we provide a review of this technology, sample preparation and analysis considerations, examples of recent biological studies, data analysis, and current outlooks. Specifically, we offer an overview of SIMS and development of the NanoSIMS. We describe the major experimental factors that should be considered prior to NanoSIMS analysis and then provide information on best practices for data analysis and image generation, which includesmore » an in-depth discussion of appropriate colormaps. Additionally, we provide an open-source method for data representation that allows simultaneous visualization of secondary electron and ion information within a single image. Lastly, we present a perspective on the future of this technology and where we think it will have the greatest impact in near future.« less

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.

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.

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.

[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.

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).

Synthetic biology: applying biological circuits beyond novel therapies.

PubMed

Dobrin, Anton; Saxena, Pratik; Fussenegger, Martin

2016-04-18

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

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.

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.

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.

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.

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).

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.

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.

BioPartsBuilder: a synthetic biology tool for combinatorial assembly of biological parts.

PubMed

Yang, Kun; Stracquadanio, Giovanni; Luo, Jingchuan; Boeke, Jef D; Bader, Joel S

2016-03-15

Combinatorial assembly of DNA elements is an efficient method for building large-scale synthetic pathways from standardized, reusable components. These methods are particularly useful because they enable assembly of multiple DNA fragments in one reaction, at the cost of requiring that each fragment satisfies design constraints. We developed BioPartsBuilder as a biologist-friendly web tool to design biological parts that are compatible with DNA combinatorial assembly methods, such as Golden Gate and related methods. It retrieves biological sequences, enforces compliance with assembly design standards and provides a fabrication plan for each fragment. BioPartsBuilder is accessible at http://public.biopartsbuilder.org and an Amazon Web Services image is available from the AWS Market Place (AMI ID: ami-508acf38). Source code is released under the MIT license, and available for download at https://github.com/baderzone/biopartsbuilder joel.bader@jhu.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

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 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 .

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.

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

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.

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

[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.

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.

MIDAS: A Modular DNA Assembly System for Synthetic Biology.

PubMed

van Dolleweerd, Craig J; Kessans, Sarah A; Van de Bittner, Kyle C; Bustamante, Leyla Y; Bundela, Rudranuj; Scott, Barry; Nicholson, Matthew J; Parker, Emily J

2018-04-20

A modular and hierarchical DNA assembly platform for synthetic biology based on Golden Gate (Type IIS restriction enzyme) cloning is described. This enabling technology, termed MIDAS (for Modular Idempotent DNA Assembly System), can be used to precisely assemble multiple DNA fragments in a single reaction using a standardized assembly design. It can be used to build genes from libraries of sequence-verified, reusable parts and to assemble multiple genes in a single vector, with full user control over gene order and orientation, as well as control of the direction of growth (polarity) of the multigene assembly, a feature that allows genes to be nested between other genes or genetic elements. We describe the detailed design and use of MIDAS, exemplified by the reconstruction, in the filamentous fungus Penicillium paxilli, of the metabolic pathway for production of paspaline and paxilline, key intermediates in the biosynthesis of a range of indole diterpenes-a class of secondary metabolites produced by several species of filamentous fungi. MIDAS was used to efficiently assemble a 25.2 kb plasmid from 21 different modules (seven genes, each composed of three basic parts). By using a parts library-based system for construction of complex assemblies, and a unique set of vectors, MIDAS can provide a flexible route to assembling tailored combinations of genes and other genetic elements, thereby supporting synthetic biology applications in a wide range of expression hosts.

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.

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.

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...

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.

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.

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

Synthetic biology to access and expand nature’s chemical diversity

PubMed Central

Smanski, Michael J.; Zhou, Hui; Claesen, Jan; Shen, Ben; Fischbach, Michael; Voigt, Christopher A.

2016-01-01

Bacterial genomes encode the biosynthetic potential to produce hundreds of thousands of complex molecules with diverse applications, from medicine to agriculture and materials. Economically accessing the potential encoded within sequenced genomes promises to reinvigorate waning drug discovery pipelines and provide novel routes to intricate chemicals. This is a tremendous undertaking, as the pathways often comprise dozens of genes spanning as much as 100+ kiliobases of DNA, are controlled by complex regulatory networks, and the most interesting molecules are made by non-model organisms. Advances in synthetic biology address these issues, including DNA construction technologies, genetic parts for precision expression control, synthetic regulatory circuits, computer aided design, and multiplexed genome engineering. Collectively, these technologies are moving towards an era when chemicals can be accessed en mass based on sequence information alone. This will enable the harnessing of metagenomic data and massive strain banks for high-throughput molecular discovery and, ultimately, the ability to forward design pathways to complex chemicals not found in nature. PMID:26876034

Synthetic Biology and the Search for Extraterrestrial Life

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2015-01-01

"Are we alone?" is one of the primary questions of astrobiology, and whose answer defines our significance in the universe. Unfortunately, this quest is hindered by the fact that we have only one confirmed example of life, that of earth. While this is enormously helpful in helping to define the minimum envelope for life, it strains credulity to imagine that life, if it arose multiple times, has not taken other routes. To help fill this gap, our lab has begun using synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - as an enabling technology. One theme, the "Hell Cell" project, focuses on creating artificial extremophiles in order to push the limits for Earth life, and to understand how difficult it is for life to evolve into extreme niches. In another project, 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.

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.

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

PubMed

Lai, Hung-En; Moore, Simon; Polizzi, Karen; Freemont, Paul

2018-01-01

Development of advanced synthetic biology tools is always in demand since they act as a platform technology to enable rapid prototyping of biological constructs in a high-throughput manner. EcoFlex is a modular cloning (MoClo) kit for Escherichia coli and is based on the Golden Gate principles, whereby Type IIS restriction enzymes (BsaI, BsmBI, BpiI) are used to construct modular genetic elements (biological parts) in a bottom-up approach. Here, we describe a collection of plasmids that stores various biological parts including promoters, RBSs, terminators, ORFs, and destination vectors, each encoding compatible overhangs allowing hierarchical assembly into single transcription units or a full-length polycistronic operon or biosynthetic pathway. A secondary module cloning site is also available for pathway optimization, in order to limit library size if necessary. Here, we show the utility of EcoFlex using the violacein biosynthesis pathway as an example.

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.

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

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.

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.

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

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 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

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.

[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.

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.

Specifications of Standards in Systems and Synthetic Biology.

PubMed

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

2015-09-04

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

Developing a Synthetic Biology Toolkit for Comamonas testosteroni, an Emerging Cellular Chassis for Bioremediation.

PubMed

Tang, Qiang; Lu, Ting; Liu, Shuang-Jiang

2018-06-12

Synthetic biology is rapidly evolving into a new phase that emphasizes real-world applications such as environmental remediation. Recently, Comamonas testosteroni has become a promising chassis for bioremediation due to its natural pollutant-degrading capacity; however, its application is hindered by the lack of fundamental gene expression tools. Here, we present a synthetic biology toolkit that enables rapid creation of functional gene circuits in C. testosteroni. We first built a shuttle system that allows efficient circuit construction in E. coli and necessary phenotypic testing in C. testosteroni. Then, we tested a set of wildtype inducible promoters, and further used a hybrid strategy to create engineered promoters to expand expression strength and dynamics. Additionally, we tested the T7 RNA Polymerase-P T7 promoter system and reduced its leaky expression through promoter mutation for gene expression. By coupling random library construction with FACS screening, we further developed a synthetic T7 promoter library to confer a wider range of expression strength and dynamic characteristics. This study provides a set of valuable tools to engineer gene circuits in C. testosteroni, facilitating the establishment of the organism as a useful microbial chassis for bioremediation purposes.

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).

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.

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.

[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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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 cascades are enabled by combining biocatalysts with artificial metalloenzymes

NASA Astrophysics Data System (ADS)

Köhler, V.; Wilson, Y. M.; Dürrenberger, M.; Ghislieri, D.; Churakova, E.; Quinto, T.; Knörr, L.; Häussinger, D.; Hollmann, F.; Turner, N. J.; Ward, T. R.

2013-02-01

Enzymatic catalysis and homogeneous catalysis offer complementary means to address synthetic challenges, both in chemistry and in biology. Despite its attractiveness, the implementation of concurrent cascade reactions that combine an organometallic catalyst with an enzyme has proven challenging because of the mutual inactivation of both catalysts. To address this, we show that incorporation of a d6-piano stool complex within a host protein affords an artificial transfer hydrogenase (ATHase) that is fully compatible with and complementary to natural enzymes, thus enabling efficient concurrent tandem catalysis. To illustrate the generality of the approach, the ATHase was combined with various NADH-, FAD- and haem-dependent enzymes, resulting in orthogonal redox cascades. Up to three enzymes were integrated in the cascade and combined with the ATHase with a view to achieving (i) a double stereoselective amine deracemization, (ii) a horseradish peroxidase-coupled readout of the transfer hydrogenase activity towards its genetic optimization, (iii) the formation of L-pipecolic acid from L-lysine and (iv) regeneration of NADH to promote a monooxygenase-catalysed oxyfunctionalization reaction.

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

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

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.

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.

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.

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.

Synthetic biology: a Jewish view.

PubMed

Glick, Shimon

2012-01-01

The discipline of synthetic biology may be one of the most dramatic advances of the past few decades. It represents a radical upgrading of humankind's ability to manipulate the world in which we live. The potential for benefits to society is enormous, but the risks for deliberate abuse or dangerous miscalculations are no less great. There are serious ethical issues, legitimate concerns for biosafety, and fears of bioterrorism. The ethical dilemmas posed are new and challenging and are being addressed by various groups and commissions. The present paper presents a Jewish approach to some of the ethical issues posed by this new technology. Judaism traditionally looks favorably on man as a co-creator with God and encourages research for the benefit of humankind. Thus it would have a positive attitude towards the current goals of synthetic biology. But in the Jewish tradition man is also charged with stewardship over nature and is admonished to preserve and nurture, not just to exploit and destroy. In line with the Presidential Commission on Bioethics, it would support a carefully weighed balance between the precautionary and the "proactionary" approaches.

[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.

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

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

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.

A novel bio-mimicking, planar nano-edge microelectrode enables enhanced long-term neural recording

NASA Astrophysics Data System (ADS)

Wijdenes, Pierre; Ali, Hasan; Armstrong, Ryden; Zaidi, Wali; Dalton, Colin; Syed, Naweed I.

2016-10-01

Our inability to accurately monitor individual neurons and their synaptic activity precludes fundamental understanding of brain function under normal and various pathological conditions. However, recent breakthroughs in micro- and nano-scale fabrication processes have advanced the development of neuro-electronic hybrid technology. Among such devices are three-dimensional and planar electrodes, offering the advantages of either high fidelity or longer-term recordings respectively. Here, we present the next generation of planar microelectrode arrays with “nano-edges” that enable long-term (≥1 month) and high fidelity recordings at a resolution 15 times higher than traditional planar electrodes. This novel technology enables better understanding of brain function and offers a tremendous opportunity towards the development of future bionic hybrids and drug discovery devices.

Elemental and isotopic imaging of biological samples using NanoSIMS.

PubMed

Kilburn, Matt R; Clode, Peta L

2014-01-01

With its low detection limits and the ability to analyze most of the elements in the periodic table, secondary ion mass spectrometry (SIMS) represents one of the most versatile in situ analytical techniques available, and recent developments have resulted in significant advantages for the use of imaging mass spectrometry in biological and biomedical research. Increases in spatial resolution and sensitivity allow detailed interrogation of samples at relevant scales and chemical concentrations. Advances in dynamic SIMS, specifically with the advent of NanoSIMS, now allow the tracking of stable isotopes within biological systems at subcellular length scales, while static SIMS combines subcellular imaging with molecular identification. In this chapter, we present an introduction to the SIMS technique, with particular reference to NanoSIMS, and discuss its application in biological and biomedical research.

Experimental Demonstration of Printed Graphene Nano-flakes Enabled Flexible and Conformable Wideband Radar Absorbers.

PubMed

Huang, Xianjun; Pan, Kewen; Hu, Zhirun

2016-12-07

In this work, we have designed, fabricated and experimentally characterized a printed graphene nano-flakes enabled flexible and conformable wideband radar absorber. The absorber covers both X (8-12 GHz) and Ku (12-18 GHz) bands and is printed on flexible substrate using graphene nano-flakes conductive ink through stencil printing method. The measured results show that an effective absorption (above 90%) bandwidth spans from 10.4 GHz to 19.7 GHz, namely a 62% fraction bandwidth, with only 2 mm thickness. The flexibility of the printed graphene nano-flakes enables the absorber conformably bending and attaching to a metal cylinder. The radar cross section (RCS) of the cylinder with and without absorber attachment has been compared and excellent absorption has been obtained. Only 3.6% bandwidth reduction has been observed comparing to that of un-bended absorber. This work has demonstrated unambiguously that printed graphene can provide flexible and conformable wideband radar absorption, which extends the graphene's application to practical RCS reductions.

Experimental Demonstration of Printed Graphene Nano-flakes Enabled Flexible and Conformable Wideband Radar Absorbers

PubMed Central

Huang, Xianjun; Pan, Kewen; Hu, Zhirun

2016-01-01

In this work, we have designed, fabricated and experimentally characterized a printed graphene nano-flakes enabled flexible and conformable wideband radar absorber. The absorber covers both X (8–12 GHz) and Ku (12–18 GHz) bands and is printed on flexible substrate using graphene nano-flakes conductive ink through stencil printing method. The measured results show that an effective absorption (above 90%) bandwidth spans from 10.4 GHz to 19.7 GHz, namely a 62% fraction bandwidth, with only 2 mm thickness. The flexibility of the printed graphene nano-flakes enables the absorber conformably bending and attaching to a metal cylinder. The radar cross section (RCS) of the cylinder with and without absorber attachment has been compared and excellent absorption has been obtained. Only 3.6% bandwidth reduction has been observed comparing to that of un-bended absorber. This work has demonstrated unambiguously that printed graphene can provide flexible and conformable wideband radar absorption, which extends the graphene’s application to practical RCS reductions. PMID:27924823

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

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.

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.

[Promoting efficiency of microbial extracellular electron transfer by synthetic biology].

PubMed

Li, Feng; Song, Hao

2017-03-25

Electroactive bacteria, including electrigenic bacteria (exoelectrogens) and electroautotrophic bacteria, implement microbial bioelectrocatalysis processes via bi-directional exchange of electrons and energy with environments, enabling a wide array of applications in environmental and energy fields, including microbial fuel cells (MFC), microbial electrolysis cells (MEC), microbial electrosynthesis (MES) to produce electricity and bulk fine chemicals. However, the low efficiency in the extracellular electron transfer (EET) of exoelectrogens and electrotrophic microbes limited their industrial applications. Here, we reviewed synthetic biology approaches to engineer electroactive microorganisms to break the bottleneck of their EET pathways, to achieve higher efficiency of EET of a number of electroactive microorganisms. Such efforts will lead to a breakthrough in the applications of these electroactive microorganisms and microbial electrocatalysis systems.

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.

Analog synthetic biology.

PubMed

Sarpeshkar, R

2014-03-28

We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations.

Analog synthetic biology

PubMed Central

Sarpeshkar, R.

2014-01-01

We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog–digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA–protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations. PMID:24567476

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

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…

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).

Could Nano-Structured Materials Enable the Improved Pressure Vessels for Deep Atmospheric Probes?

NASA Technical Reports Server (NTRS)

Srivastava, D.; Fuentes, A.; Bienstock, B.; Arnold, J. O.

2005-01-01

A viewgraph presentation on the use of Nano-Structured Materials to enable pressure vessel structures for deep atmospheric probes is shown. The topics include: 1) High Temperature/Pressure in Key X-Environments; 2) The Case for Use of Nano-Structured Materials Pressure Vessel Design; 3) Carbon based Nanomaterials; 4) Nanotube production & purification; 5) Nanomechanics of Carbon Nanotubes; 6) CNT-composites: Example (Polymer); 7) Effect of Loading sequence on Composite with 8% by volume; 8) Models for Particulate Reinforced Composites; 9) Fullerene/Ti Composite for High Strength-Insulating Layer; 10) Fullerene/Epoxy Composite for High Strength-Insulating Layer; 11) Models for Continuous Fiber Reinforced Composites; 12) Tensile Strength for Discontinuous Fiber Composite; 13) Ti + SWNT Composites: Thermal/Mechanical; 14) Ti + SWNT Composites: Tensile Strength; and 15) Nano-structured Shell for Pressure Vessels.

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

On Beyond Star Trek: Synthetic Biology and the Future of Space Exploration

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2017-01-01

A turtle carries its own habitat. While it is reliable, it costs energy. NASA makes the same trade-off when it transports habitats and other structures needed to lunar and planetary surfaces increasing upmass, and affecting other mission goals. Long-term human space presence requires periodic replenishment, adding a massive cost overhead. Even robotic missions often sacrifice science goals for heavy radiation and thermal protection. Biology has the potential to solve these problems because it can replicate and repair itself, and do a wide variety of chemical reactions including making food, fuel and materials. Synthetic biology enhances and expands life's evolved repertoire. Using organisms as feedstock, additive manufacturing could make possible the dream of producing bespoke tools, food, smart fabrics and even replacement organs on demand. Imagine what new products can be enabled by such a technology, on earth or beyond!

Synthetic biology of antimicrobial discovery.

PubMed

Zakeri, Bijan; Lu, Timothy K

2013-07-19

Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug-resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery.

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.

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.

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…

Fabrication, Characterization, and Biological Activity of Avermectin Nano-delivery Systems with Different Particle Sizes

NASA Astrophysics Data System (ADS)

Wang, Anqi; Wang, Yan; Sun, Changjiao; Wang, Chunxin; Cui, Bo; Zhao, Xiang; Zeng, Zhanghua; Yao, Junwei; Yang, Dongsheng; Liu, Guoqiang; Cui, Haixin

2018-01-01

Nano-delivery systems for the active ingredients of pesticides can improve the utilization rates of pesticides and prolong their control effects. This is due to the nanocarrier envelope and controlled release function. However, particles containing active ingredients in controlled release pesticide formulations are generally large and have wide size distributions. There have been limited studies about the effect of particle size on the controlled release properties and biological activities of pesticide delivery systems. In the current study, avermectin (Av) nano-delivery systems were constructed with different particle sizes and their performances were evaluated. The Av release rate in the nano-delivery system could be effectively controlled by changing the particle size. The biological activity increased with decreasing particle size. These results suggest that Av nano-delivery systems can significantly improve the controllable release, photostability, and biological activity, which will improve efficiency and reduce pesticide residues.

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.

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.

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.

Multiplexed genome engineering and genotyping methods applications for synthetic biology and metabolic engineering.

PubMed

Wang, Harris H; Church, George M

2011-01-01

Engineering at the scale of whole genomes requires fundamentally new molecular biology tools. Recent advances in recombineering using synthetic oligonucleotides enable the rapid generation of mutants at high efficiency and specificity and can be implemented at the genome scale. With these techniques, libraries of mutants can be generated, from which individuals with functionally useful phenotypes can be isolated. Furthermore, populations of cells can be evolved in situ by directed evolution using complex pools of oligonucleotides. Here, we discuss ways to utilize these multiplexed genome engineering methods, with special emphasis on experimental design and implementation. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

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.

Synthetic biology of antimicrobial discovery

PubMed Central

Zakeri, Bijan; Lu, Timothy K.

2012-01-01

Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251

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

Toward responsible development and effective risk management of nano-enabled products in the U.S. construction industry

NASA Astrophysics Data System (ADS)

West, Gavin H.; Lippy, Bruce E.; Cooper, Michael R.; Marsick, Daniel; Burrelli, Leonard G.; Griffin, Kelsey N.; Segrave, Alan M.

2016-02-01

The global construction sector is experiencing major improvements to building materials used in large quantities through commercial applications of nanotechnology. Nano-enabled construction products hold great promise for energy efficiency and resource conservation, but risk assessments lag as new products emerge. This paper presents results from an inventory, survey, and exposure assessment conducted by the authors and explores these findings in the broader context of evolving research trends and responsible development of nanotechnology. An inventory of 458 reportedly nano-enabled construction products provided insight into product availability, potential exposures, and deficiencies in risk communication that are barriers to adoption of proactive safety measures. Seasoned construction trainers surveyed were largely unaware of the availability of nano-enabled construction products. Exposure assessment demonstrated the effectiveness of ventilation to reduce exposures during mechanical abrasion of photocatalytic tiles containing titanium dioxide (TiO2). Dissociated particles of TiO2 just above the nanoscale (138 nm) were detected in the debris collected during cutting of the tiles, but measurements were below recommended exposure limits for TiO2. Exposure assessments remain scarce, and toxicological understanding primarily pertains to unincorporated nanomaterials; less is known about the occupational risks of nano-enabled construction products across their life cycle. Further research is needed to characterize and quantify exposure to debris released from nanocomposite materials for realistic risk assessment, and to ascertain how nanocomposite matrices, fillers, and degradation forces interact to affect release dynamics. Improving risk communication strategies and implementing safe work practices will cultivate responsible development of nanotechnology in construction, as will multidisciplinary research efforts.

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.

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: 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

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

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: 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.

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.

High molecular weight DNA assembly in vivo for synthetic biology applications.

PubMed

Juhas, Mario; Ajioka, James W

2017-05-01

DNA assembly is the key technology of the emerging interdisciplinary field of synthetic biology. While the assembly of smaller DNA fragments is usually performed in vitro, high molecular weight DNA molecules are assembled in vivo via homologous recombination in the host cell. Escherichia coli, Bacillus subtilis and Saccharomyces cerevisiae are the main hosts used for DNA assembly in vivo. Progress in DNA assembly over the last few years has paved the way for the construction of whole genomes. This review provides an update on recent synthetic biology advances with particular emphasis on high molecular weight DNA assembly in vivo in E. coli, B. subtilis and S. cerevisiae. Special attention is paid to the assembly of whole genomes, such as those of the first synthetic cell, synthetic yeast and minimal genomes.

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.

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 for pharmaceutical drug discovery

PubMed Central

Trosset, Jean-Yves; Carbonell, Pablo

2015-01-01

Synthetic biology (SB) is an emerging discipline, which is slowly reorienting the field of drug discovery. For thousands of years, living organisms such as plants were the major source of human medicines. The difficulty in resynthesizing natural products, however, often turned pharmaceutical industries away from this rich source for human medicine. More recently, progress on transformation through genetic manipulation of biosynthetic units in microorganisms has opened the possibility of in-depth exploration of the large chemical space of natural products derivatives. Success of SB in drug synthesis culminated with the bioproduction of artemisinin by microorganisms, a tour de force in protein and metabolic engineering. Today, synthetic cells are not only used as biofactories but also used as cell-based screening platforms for both target-based and phenotypic-based approaches. Engineered genetic circuits in synthetic cells are also used to decipher disease mechanisms or drug mechanism of actions and to study cell–cell communication within bacteria consortia. This review presents latest developments of SB in the field of drug discovery, including some challenging issues such as drug resistance and drug toxicity. PMID:26673570

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

[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.

Nanotechnologies for Composite Structures- From Nanocomposites to Multifunctional Nano-Enabled Fibre Reinforced Composites for Spacecrafts

NASA Astrophysics Data System (ADS)

Kostopoulos, Vassilis; Vavouliotis, Antonios; Baltopoulos, Athanasios; Sotiririadis, George; Masouras, Athanasios; Pambaguian, Laurent

2014-06-01

The past decade, extensive efforts have been invested in understanding the nano-scale and revealing the capabilities offered by nanotechnology products to structural materials. Nevertheless, a major issue faced lately more seriously due to the interest of industry is on how to incorporate these nano-species into the final composite structure through existing manufacturing processes and infrastructure. In this work, we present the experience obtained from the latest nanotechnology research activities supported by ESA. The paper focuses on prepreg composite manufacturing technology and addresses:- Approaches for nano-enabling of composites- Up-scaling strategies towards final structures- Latest results on performance of nano-enabledfiber reinforced compositesSeveral approaches for the utilization of nanotechnology products in structural composite structures have been proposed and are reviewed, in short along with respective achieved results. A variety of nano-fillers has been proposed and employed, individually or in combination in hybrid forms, to approach the desired performance. A major part of the work deals with the up-scaling routes of these technologies to reach final products and industrial scales and processes while meeting end-user performance.

Engineering genetic circuit interactions within and between synthetic minimal cells

NASA Astrophysics Data System (ADS)

Adamala, Katarzyna P.; Martin-Alarcon, Daniel A.; Guthrie-Honea, Katriona R.; Boyden, Edward S.

2017-05-01

Genetic circuits and reaction cascades are of great importance for synthetic biology, biochemistry and bioengineering. An open question is how to maximize the modularity of their design to enable the integration of different reaction networks and to optimize their scalability and flexibility. One option is encapsulation within liposomes, which enables chemical reactions to proceed in well-isolated environments. Here we adapt liposome encapsulation to enable the modular, controlled compartmentalization of genetic circuits and cascades. We demonstrate that it is possible to engineer genetic circuit-containing synthetic minimal cells (synells) to contain multiple-part genetic cascades, and that these cascades can be controlled by external signals as well as inter-liposomal communication without crosstalk. We also show that liposomes that contain different cascades can be fused in a controlled way so that the products of incompatible reactions can be brought together. Synells thus enable a more modular creation of synthetic biology cascades, an essential step towards their ultimate programmability.

Synthetic Biology of Polyhydroxyalkanoates (PHA).

PubMed

Meng, De-Chuan; Chen, Guo-Qiang

Microbial polyhydroxyalkanoates (PHA) are a family of biodegradable and biocompatible polyesters which have been extensively studied using synthetic biology and metabolic engineering methods for improving production and for widening its diversity. Synthetic biology has allowed PHA to become composition controllable random copolymers, homopolymers, and block copolymers. Recent developments showed that it is possible to establish a microbial platform for producing not only random copolymers with controllable monomers and their ratios but also structurally defined homopolymers and block copolymers. This was achieved by engineering the genome of Pseudomonas putida or Pseudomonas entomophiles to weaken the β-oxidation and in situ fatty acid synthesis pathways, so that a fatty acid fed to the bacteria maintains its original chain length and structures when incorporated into the PHA chains. The engineered bacterium allows functional groups in a fatty acid to be introduced into PHA, forming functional PHA, which, upon grafting, generates endless PHA variety. Recombinant Escherichia coli also succeeded in producing efficiently poly(3-hydroxypropionate) or P3HP, the strongest member of PHA. Synthesis pathways of P3HP and its copolymer P3HB3HP of 3-hydroxybutyrate and 3-hydroxypropionate were assembled respectively to allow their synthesis from glucose. CRISPRi was also successfully used to manipulate simultaneously multiple genes and control metabolic flux in E. coli to obtain a series of copolymer P3HB4HB of 3-hydroxybutyrate (3HB) and 4-hydroxybutyrate (4HB). The bacterial shapes were successfully engineered for enhanced PHA accumulation.

Genomics-Based Discovery of Plant Genes for Synthetic Biology of Terpenoid Fragrances: A Case Study in Sandalwood oil Biosynthesis.

PubMed

Celedon, J M; Bohlmann, J

2016-01-01

Terpenoid fragrances are powerful mediators of ecological interactions in nature and have a long history of traditional and modern industrial applications. Plants produce a great diversity of fragrant terpenoid metabolites, which make them a superb source of biosynthetic genes and enzymes. Advances in fragrance gene discovery have enabled new approaches in synthetic biology of high-value speciality molecules toward applications in the fragrance and flavor, food and beverage, cosmetics, and other industries. Rapid developments in transcriptome and genome sequencing of nonmodel plant species have accelerated the discovery of fragrance biosynthetic pathways. In parallel, advances in metabolic engineering of microbial and plant systems have established platforms for synthetic biology applications of some of the thousands of plant genes that underlie fragrance diversity. While many fragrance molecules (eg, simple monoterpenes) are abundant in readily renewable plant materials, some highly valuable fragrant terpenoids (eg, santalols, ambroxides) are rare in nature and interesting targets for synthetic biology. As a representative example for genomics/transcriptomics enabled gene and enzyme discovery, we describe a strategy used successfully for elucidation of a complete fragrance biosynthetic pathway in sandalwood (Santalum album) and its reconstruction in yeast (Saccharomyces cerevisiae). We address questions related to the discovery of specific genes within large gene families and recovery of rare gene transcripts that are selectively expressed in recalcitrant tissues. To substantiate the validity of the approaches, we describe the combination of methods used in the gene and enzyme discovery of a cytochrome P450 in the fragrant heartwood of tropical sandalwood, responsible for the fragrance defining, final step in the biosynthesis of (Z)-santalols. © 2016 Elsevier Inc. All rights reserved.

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.

Synthetic Biology Guides Biofuel Production

PubMed Central

Connor, Michael R.; Atsumi, Shota

2010-01-01

The advancement of microbial processes for the production of renewable liquid fuels has increased with concerns about the current fuel economy. The development of advanced biofuels in particular has risen to address some of the shortcomings of ethanol. These advanced fuels have chemical properties similar to petroleum-based liquid fuels, thus removing the need for engine modification or infrastructure redesign. While the productivity and titers of each of these processes remains to be improved, progress in synthetic biology has provided tools to guide the engineering of these processes through present and future challenges. PMID:20827393

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.

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.

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

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.

Mapping the Emergence of Synthetic Biology

PubMed Central

2016-01-01

In this paper, we apply an original scientometric analyses to a corpus comprising synthetic biology (SynBio) publications in Thomson Reuters Web of Science to characterize the emergence of this new scientific field. Three results were drawn from this empirical investigation. First, despite the exponential growth of publications, the study of population level statistics (newcomers proportion, collaboration network structure) shows that SynBio has entered a stabilization process since 2010. Second, the mapping of textual and citational networks shows that SynBio is characterized by high heterogeneity and four different approaches: the central approach, where biobrick engineering is the most widespread; genome engineering; protocell creation; and metabolic engineering. We suggest that synthetic biology acts as an umbrella term allowing for the mobilization of resources, and also serves to relate scientific content and promises of applications. Third, we observed a strong intertwinement between epistemic and socio-economic dynamics. Measuring scientific production and impact and using structural analysis data, we identified a core set of mostly American scientists. Biographical analysis shows that these central and influential scientists act as “boundary spanners,” meaning that their importance to the field lies not only in their academic contributions, but also in their capacity to interact with other social spaces that are outside the academic sphere. PMID:27611324

[Application of synthetic biology in environmental remediation].

PubMed

Tang, Hongzhi; Wang, Weiwei; Zhang, Lige; Huang, Ling; Lu, Xinyu; Xu, Ping

2017-03-25

Environmental problems are the most serious challenges in the 21st century. With the rapid development of modern industry and agriculture, ecological and environmental deterioration have become the most important factors to restrict the sustainable development of social economy. Microbial cells have strong ability for environmental remediation, but their evolution speed is slower than the speed of emerging pollutants. Therefore, the treatment using the synthetic biology is in urgent need. Full understanding of the microbial degradation characteristics (pathways) of refractory organic pollutants with the help of abundant microbial and gene resources in China is important. Using synthetic biology to redesign and transform the existing degrading strain will be used to degrade particular organic pollutants or multiple organic pollutants. For the complex pollutants, such as wastewater, based on the establishment of metabolic or regulation or resistance related gene modules of typical organic pollutants, artificial flora could be designed to solve the complex pollutants. The rational design and construction of engineering bacteria for typical environmental organic pollutants can effectively promote microbial catabolism of emerging contaminants, providing technical support for environmental remediation in China.

New Frontiers in Synthetic Biology for Spaceflight

NASA Technical Reports Server (NTRS)

Galazka, Jonathan M.

2017-01-01

Exploration of the solar system is constrained by the cost of moving mass off Earth. Producing materials in situ will reduce the mass that must be delivered from earth. CO2 is abundant on Mars and manned spacecraft. On the ISS, NASA reacts excess CO2 with H2 to generate CH4 and H2O using the Sabatier System. The resulting water is recovered into the ISS, but the methane is vented to space. Thus, there is a capability need for systems that convert methane into valuable materials. Methanotrophic bacteria consume methane but these are poor synthetic biology platforms. Thus, there is a knowledge gap in utilizing methane in a robust and flexible synthetic biology platform. The yeast Pichia pastoris is a refined microbial factory that is used widely by industry because it efficiently secretes products. Pichia could produce a variety of useful products in space. Pichia does not consume methane but robustly consumes methanol, which is one enzymatic step removed from methane. Our goal is to engineer Pichia to consume methane thereby creating a powerful methane-consuming microbial factory.

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

Multi-functional photonic crystal sensors enabled by biological silica (Conference Presentation)

NASA Astrophysics Data System (ADS)

Wang, Alan X.

2017-02-01

Diatoms are microalgae found in every habitat where water is present. They produce 40% of the ocean's yearly production of organic carbon and 20% of the oxygen that we breathe. Their abundance and wide distribution make them ideal materials for a wide range of applications as living organisms. In our previous work, we have demonstrated that diatom biosilica with self-assembled silver nanoparticles (Ag NPs) can be used as ultra-sensitive, low-cost substrates for surface-enhanced Raman scattering (SERS) sensing. The enhancement comes from the photonic crystal enhancement of diatom frustules that could improve the hot-spots of Ag NPs. In this work, we report the unique micro-fluidic flow, analyte concentration effect, and thin layer chromatography (TLC) on diatom biosilica, which enables selection, separation, detection, and analysis of complex chemical and biological samples. Particularly, we show that the microscopic fluidic flow induced by the evaporation of liquid droplet can concentrate the analyte and achieve label-free sensing of single molecule detection of R6G and label-free sensing of 4.5×10-17g trinitrotoluene (TNT) from only 200 nano-liter solution. We also demonstrated a facile method for instant on-site separation and detection of analytes by TLC in tandem with SERS spectroscopy using high density diatom thin film. This lab-on-chip technology has been successfully applied for label-free detection of polycyclic aromatic hydrocarbons from human plasma and histamine from salmon fish. Our research suggests that such cost-effective, multi-functional photonic crystal sensors enabled by diatom biosilica opens a new route for lab-on-chip systems and possess significant engineering potentials for chemical and biological sensing.

Two sides of the same coin? The (techno)epistemic cultures of systems and synthetic biology.

PubMed

Kastenhofer, Karen

2013-06-01

Systems and synthetic biology both emerged around the turn of this century as labels for new research approaches. Although their disciplinary status as well as their relation to each other is rarely discussed in depth, now and again the idea is invoked that both approaches represent 'two sides of the same coin'. The following paper focuses on this general notion and compares it with empirical findings concerning the epistemic cultures prevalent in the two contexts. Drawing on interviews with researchers from both fields, on participatory observation in conferences and courses and on documentary analysis, this paper delineates differences and similarities, incompatibilities and blurred boundaries. By reconstructing systems and synthetic biology's epistemic cultures, this paper argues that they represent two 'communities of vision', encompassing heterogeneous practices. Understanding the relation of the respective visions of understanding nature and engineering life is seen as indispensible for the characterisation of (techno)science in more general terms. Depending on the conceptualisation of understanding and construction (or: science and engineering), related practices such as in silico modelling for enhancing understanding or enabling engineering can either be seen as incommensurable or 'two sides of one coin'. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

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 biology. Genomically encoded analog memory with precise in vivo DNA writing in living cell populations.

PubMed

Farzadfard, Fahim; Lu, Timothy K

2014-11-14

Cellular memory is crucial to many natural biological processes and sophisticated synthetic biology applications. Existing cellular memories rely on epigenetic switches or recombinases, which are limited in scalability and recording capacity. In this work, we use the DNA of living cell populations as genomic "tape recorders" for the analog and distributed recording of long-term event histories. We describe a platform for generating single-stranded DNA (ssDNA) in vivo in response to arbitrary transcriptional signals. When coexpressed with a recombinase, these intracellularly expressed ssDNAs target specific genomic DNA addresses, resulting in precise mutations that accumulate in cell populations as a function of the magnitude and duration of the inputs. This platform could enable long-term cellular recorders for environmental and biomedical applications, biological state machines, and enhanced genome engineering strategies. Copyright © 2014, American Association for the Advancement of Science.

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

Fundamental plant biology enabled by the space shuttle.

PubMed

Paul, Anna-Lisa; Wheeler, Ray M; Levine, Howard G; Ferl, Robert J

2013-01-01

The relationship between fundamental plant biology and space biology was especially synergistic in the era of the Space Shuttle. While all terrestrial organisms are influenced by gravity, the impact of gravity as a tropic stimulus in plants has been a topic of formal study for more than a century. And while plants were parts of early space biology payloads, it was not until the advent of the Space Shuttle that the science of plant space biology enjoyed expansion that truly enabled controlled, fundamental experiments that removed gravity from the equation. The Space Shuttle presented a science platform that provided regular science flights with dedicated plant growth hardware and crew trained in inflight plant manipulations. Part of the impetus for plant biology experiments in space was the realization that plants could be important parts of bioregenerative life support on long missions, recycling water, air, and nutrients for the human crew. However, a large part of the impetus was that the Space Shuttle enabled fundamental plant science essentially in a microgravity environment. Experiments during the Space Shuttle era produced key science insights on biological adaptation to spaceflight and especially plant growth and tropisms. In this review, we present an overview of plant science in the Space Shuttle era with an emphasis on experiments dealing with fundamental plant growth in microgravity. This review discusses general conclusions from the study of plant spaceflight biology enabled by the Space Shuttle by providing historical context and reviews of select experiments that exemplify plant space biology science.

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.

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.

A novel melittin nano-liposome exerted excellent anti-hepatocellular carcinoma efficacy with better biological safety.

PubMed

Mao, Jie; Liu, Shujun; Ai, Min; Wang, Zhuo; Wang, Duowei; Li, Xianjing; Hu, Kaiyong; Gao, Xinghua; Yang, Yong

2017-03-20

Melittin is the main effective component of bee venom and has extensive biological functions; however, serious side effects have restricted its clinical application. Preclinical and clinical studies showed that the main adverse events were allergic reaction and pain at the administration site. To decrease the toxicity, we prepared melittin nano-liposomes by encapsulating melittin with poloxamer 188 and explored the inhibitory activities on liver cancer together with biological safety. Here, we showed that melittin nano-liposomes significantly inhibited the survival of hepatocellular carcinoma (HCC) cells in vitro and prominently suppressed the growth of subcutaneous and orthotopic HCC transplantation tumors in vivo. It was important that it induced less inflammation and allergy in mice compared with melittin. Overall, melittin nano-liposomes would have a better application in HCC therapy due to its significant anti-tumor activity and better biological safety.

Metabolomics, Standards, and Metabolic Modeling for Synthetic Biology in Plants

PubMed Central

Hill, Camilla Beate; Czauderna, Tobias; Klapperstück, Matthias; Roessner, Ute; Schreiber, Falk

2015-01-01

Life on earth depends on dynamic chemical transformations that enable cellular functions, including electron transfer reactions, as well as synthesis and degradation of biomolecules. Biochemical reactions are coordinated in metabolic pathways that interact in a complex way to allow adequate regulation. Biotechnology, food, biofuel, agricultural, and pharmaceutical industries are highly interested in metabolic engineering as an enabling technology of synthetic biology to exploit cells for the controlled production of metabolites of interest. These approaches have only recently been extended to plants due to their greater metabolic complexity (such as primary and secondary metabolism) and highly compartmentalized cellular structures and functions (including plant-specific organelles) compared with bacteria and other microorganisms. Technological advances in analytical instrumentation in combination with advances in data analysis and modeling have opened up new approaches to engineer plant metabolic pathways and allow the impact of modifications to be predicted more accurately. In this article, we review challenges in the integration and analysis of large-scale metabolic data, present an overview of current bioinformatics methods for the modeling and visualization of metabolic networks, and discuss approaches for interfacing bioinformatics approaches with metabolic models of cellular processes and flux distributions in order to predict phenotypes derived from specific genetic modifications or subjected to different environmental conditions. PMID:26557642

Synthetic biology strategies toward heterologous phytochemical production.

PubMed

Kotopka, Benjamin J; Li, Yanran; Smolke, Christina D

2018-06-13

Covering: 2006 to 2018Phytochemicals are important sources for the discovery and development of agricultural and pharmaceutical compounds, such as pesticides and medicines. However, these compounds are typically present in low abundance in nature, and the biosynthetic pathways for most phytochemicals are not fully elucidated. Heterologous production of phytochemicals in plant, bacterial, and yeast hosts has been pursued as a potential approach to address sourcing issues associated with many valuable phytochemicals, and more recently has been utilized as a tool to aid in the elucidation of plant biosynthetic pathways. Due to the structural complexity of certain phytochemicals and the associated biosynthetic pathways, reconstitution of plant pathways in heterologous hosts can encounter numerous challenges. Synthetic biology approaches have been developed to address these challenges in areas such as precise control over heterologous gene expression, improving functional expression of heterologous enzymes, and modifying central metabolism to increase the supply of precursor compounds into the pathway. These strategies have been applied to advance plant pathway reconstitution and phytochemical production in a wide variety of heterologous hosts. Here, we review synthetic biology strategies that have been recently applied to advance complex phytochemical production in heterologous hosts.

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

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

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

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

Synthetic Biology and the Gut Microbiome.

PubMed

Dou, Jennifer; Bennett, Matthew R

2018-05-01

The gut microbiome plays a crucial role in maintaining human health. Functions performed by gastrointestinal microbes range from regulating metabolism to modulating immune and nervous system development. Scientists have attempted to exploit this importance through the development of engineered probiotics that are capable of producing and delivering small molecule therapeutics within the gut. However, existing synthetic probiotics are simplistic and fail to replicate the complexity and adaptability of native homeostatic mechanisms. In this review, the ways in which the tools and approaches of synthetic biology have been applied to improve the efficacy of therapeutic probiotics, and the ways in which they might be applied in the future is discussed. Simple devices, such as a bistable switches and integrase memory arrays, have been successfully implemented in the mammalian gut, and models for targeted delivery in this environment have also been developed. In the future, it will be necessary to introduce concepts such as logic-gating and biocontainment mechanisms into synthetic probiotics, as well as to expand the collection of relevant biosensors. Ideally, this will bring us closer to a reality in which engineered therapeutic microbes will be able to accurately diagnose and effectively respond to a variety of disease states. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Thermal decomposition of nano-enabled thermoplastics: Possible environmental health and safety implications

PubMed Central

Sotiriou, Georgios A.; Singh, Dilpreet; Zhang, Fang; Chalbot, Marie-Cecile G.; Spielman-Sun, Eleanor; Hoering, Lutz; Kavouras, Ilias G.; Lowry, Gregory V.; Wohlleben, Wendel; Demokritou, Philip

2015-01-01

Nano-enabled products (NEPs) are currently part of our life prompting for detailed investigation of potential nano-release across their life-cycle. Particularly interesting is their end-of-life thermal decomposition scenario. Here, we examine the thermal decomposition of a widely used NEP, namely thermoplastic nanocomposites, and assess the properties of the byproducts (released aerosol and residual ash) and possible environmental health and safety implications. We focus on establishing a fundamental understanding on the effect of thermal decomposition parameters, such as polymer matrix, nanofiller properties, decomposition temperature, on the properties of byproducts using a recently-developed lab-based experimental integrated platform. Our results indicate that thermoplastic polymer matrix strongly influences size and morphology of released aerosol, while there was minimal but detectable nano-release, especially when inorganic nanofillers were used. The chemical composition of the released aerosol was found not to be strongly influenced by the presence of nanofiller at least for the low, industry-relevant loadings assessed here. Furthermore, the morphology and composition of residual ash was found to be strongly influenced by the presence of nanofiller. The findings presented here on thermal decomposition/incineration of NEPs raise important questions and concerns regarding the potential fate and transport of released engineered nanomaterials in environmental media and potential environmental health and safety implications. PMID:26642449

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

The Chemo-Biological Outreach of Nano-Biomaterials: Implications for Tissue Engineering and Regenerative Medicine.

PubMed

Kumar, Pradeep; Choonara, Yahya E; Khan, Riaz A; Pillay, Viness

2017-01-01

Nanobiomaterials can be defined as materials interacting with and influencing the biological microenvironment at a nanointerface. Recently the basic as well as applied research related to nanobiomaterials - a conjugation of nano-, material- and life-sciences - has immensely evolved for therapeutics and related biotechnology areas. The current overview focused on the potential of nanobiomaterial-based substrates towards the generation of biocompatible surfaces, tissue engineering architectures, and regenerative medicine. Emphasis was given to chemomolecular functionalization of nanobiomaterials, nanobiomaterial composites, and morphomechanically modified nanoarchetypes and their inherent chemo-biological interaction with the biological microenvironment. Additionally, recent developments in nanobiomaterial substrate design and structure, chemo-biological interface related bio-systems uses and further evolving applications in health care, therapeutics and nanomedicine were discussed herein. Furthermore, a special emphasis was placed on the nano-chemo-biological interactions inherent to various nanobiomaterial substrates in close vicinity with biological systems. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Nanofiller Presence Enhances Polycyclic Aromatic Hydrocarbon (PAH) Profile on Nanoparticles Released during Thermal Decomposition of Nano-enabled Thermoplastics: Potential Environmental Health Implications.

PubMed

Singh, Dilpreet; Schifman, Laura Arabella; Watson-Wright, Christa; Sotiriou, Georgios A; Oyanedel-Craver, Vinka; Wohlleben, Wendel; Demokritou, Philip

2017-05-02

Nano-enabled products are ultimately destined to reach end-of-life with an important fraction undergoing thermal degradation through waste incineration or accidental fires. Although previous studies have investigated the physicochemical properties of released lifecycle particulate matter (called LCPM) from thermal decomposition of nano-enabled thermoplastics, critical questions about the effect of nanofiller on the chemical composition of LCPM still persist. Here, we investigate the potential nanofiller effects on the profiles of 16 Environmental Protection Agency (EPA)-priority polycyclic aromatic hydrocarbons (PAHs) adsorbed on LCPM from thermal decomposition of nano-enabled thermoplastics. We found that nanofiller presence in thermoplastics significantly enhances not only the total PAH concentration in LCPM but most importantly also the high molecular weight (HMW, 4-6 ring) PAHs that are considerably more toxic than the low molecular weight (LMW, 2-3 ring) PAHs. This nano-specific effect was also confirmed during in vitro cellular toxicological evaluation of LCPM for the case of polyurethane thermoplastic enabled with carbon nanotubes (PU-CNT). LCPM from PU-CNT shows significantly higher cytotoxicity compared to PU which could be attributed to its higher HMW PAH concentration. These findings are crucial and make the case that nanofiller presence in thermoplastics can significantly affect the physicochemical and toxicological properties of LCPM released during thermal decomposition.

Modular electron transfer circuits for synthetic biology

PubMed Central

Agapakis, Christina M

2010-01-01

Electron transfer is central to a wide range of essential metabolic pathways, from photosynthesis to fermentation. The evolutionary diversity and conservation of proteins that transfer electrons makes these pathways a valuable platform for engineered metabolic circuits in synthetic biology. Rational engineering of electron transfer pathways containing hydrogenases has the potential to lead to industrial scale production of hydrogen as an alternative source of clean fuel and experimental assays for understanding the complex interactions of multiple electron transfer proteins in vivo. We designed and implemented a synthetic hydrogen metabolism circuit in Escherichia coli that creates an electron transfer pathway both orthogonal to and integrated within existing metabolism. The design of such modular electron transfer circuits allows for facile characterization of in vivo system parameters with applications toward further engineering for alternative energy production. PMID:21468209

Nano-Enabled Approaches to Chemical Imaging in Biosystems

DOE PAGES

Retterer, Scott T.; Morrell-Falvey, Jennifer L.; Doktycz, Mitchel John

2018-02-28

Understanding and predicting how biosystems function require knowledge about the dynamic physicochemical environments with which they interact and alter by their presence. Yet, identifying specific components, tracking the dynamics of the system, and monitoring local environmental conditions without disrupting biosystem function present significant challenges for analytical measurements. Nanomaterials, by their very size and nature, can act as probes and interfaces to biosystems and offer solutions to some of these challenges. At the nanoscale, material properties emerge that can be exploited for localizing biomolecules and making chemical measurements at cellular and subcellular scales. Here, we review advances in chemical imaging enabledmore » by nanoscale structures, in the use of nanoparticles as chemical and environmental probes, and in the development of micro- and nanoscale fluidic devices to define and manipulate local environments and facilitate chemical measurements of complex biosystems. As a result, integration of these nano-enabled methods will lead to an unprecedented understanding of biosystem function.« less

Nano-Enabled Approaches to Chemical Imaging in Biosystems

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

Retterer, Scott T.; Morrell-Falvey, Jennifer L.; Doktycz, Mitchel John

Understanding and predicting how biosystems function require knowledge about the dynamic physicochemical environments with which they interact and alter by their presence. Yet, identifying specific components, tracking the dynamics of the system, and monitoring local environmental conditions without disrupting biosystem function present significant challenges for analytical measurements. Nanomaterials, by their very size and nature, can act as probes and interfaces to biosystems and offer solutions to some of these challenges. At the nanoscale, material properties emerge that can be exploited for localizing biomolecules and making chemical measurements at cellular and subcellular scales. Here, we review advances in chemical imaging enabledmore » by nanoscale structures, in the use of nanoparticles as chemical and environmental probes, and in the development of micro- and nanoscale fluidic devices to define and manipulate local environments and facilitate chemical measurements of complex biosystems. As a result, integration of these nano-enabled methods will lead to an unprecedented understanding of biosystem function.« less

Suture, synthetic, or biologic in contaminated ventral hernia repair.

PubMed

Bondre, Ioana L; Holihan, Julie L; Askenasy, Erik P; Greenberg, Jacob A; Keith, Jerrod N; Martindale, Robert G; Roth, J Scott; Liang, Mike K

2016-02-01

Data are lacking to support the choice between suture, synthetic mesh, or biologic matrix in contaminated ventral hernia repair (VHR). We hypothesize that in contaminated VHR, suture repair is associated with the lowest rate of surgical site infection (SSI). A multicenter database of all open VHR performed at from 2010-2011 was reviewed. All patients with follow-up of 1 mo and longer were included. The primary outcome was SSI as defined by the Centers for Disease Control and Prevention. The secondary outcome was hernia recurrence (assessed clinically or radiographically). Multivariate analysis (stepwise regression for SSI and Cox proportional hazard model for recurrence) was performed. A total of 761 VHR were reviewed for a median (range) follow-up of 15 (1-50) mo: there were 291(38%) suture, 303 (40%) low-density and/or mid-density synthetic mesh, and 167(22%) biologic matrix repair. On univariate analysis, there were differences in the three groups including ethnicity, ASA, body mass index, institution, diabetes, primary versus incisional hernia, wound class, hernia size, prior VHR, fascial release, skin flaps, and acute repair. The unadjusted outcomes for SSI (15.1%; 17.8%; 21.0%; P = 0.280) and recurrence (17.8%; 13.5%; 21.5%; P = 0.074) were not statistically different between groups. On multivariate analysis, biologic matrix was associated with a nonsignificant reduction in both SSI and recurrences, whereas synthetic mesh associated with fewer recurrences compared to suture (hazard ratio = 0.60; P = 0.015) and nonsignificant increase in SSI. Interval estimates favored biologic matrix repair in contaminated VHR; however, these results were not statistically significant. In the absence of higher level evidence, surgeons should carefully balance risk, cost, and benefits in managing contaminated ventral hernia repair. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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.

Hybrid biological, electron beam and zero-valent nano iron treatment of recalcitrant metalworking fluids.

PubMed

Thill, Patrick G; Ager, Duane K; Vojnovic, Borivoj; Tesh, Sarah J; Scott, Thomas B; Thompson, Ian P

2016-04-15

Hybrid approaches for the remediation and detoxification of toxic recalcitrant industrial wastewater were investigated. The focus was waste metalworking fluid, which was selected as a representative model of other waste streams that are toxic, recalcitrant and that require more sustainable routes of safe disposal. The hybrid approaches included biodegradation, electron beam irradiation and zero-valent nano iron advanced oxidation processes that were employed individually and in sequence employing a factorial design. To compare process performance operationally exhausted and pristine metalworking fluid were compared. Sequential hybrid electron beam irradiation, biological, nanoscale zero-valent iron and biological treatment lead to synergistic detoxification and degradation of both recalcitrant streams, as determined by complementary surrogates and lead to overall improved COD removal of 92.8 ± 1.4% up from 85.9 ± 3.4% for the pristine metalworking fluid. Electron beam pre-treatment enabled more effective biotreatment, achieving 69.5 ± 8% (p = 0.005) and 24.6 ± 4.8% (p = 0.044) COD reductions. Copyright © 2016. Published by Elsevier Ltd.

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

PubMed

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 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. © 2014 A. M. Campbell et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

"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.

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.

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

Chemotactic synthetic vesicles: Design and applications in blood-brain barrier crossing.

PubMed

Joseph, Adrian; Contini, Claudia; Cecchin, Denis; Nyberg, Sophie; Ruiz-Perez, Lorena; Gaitzsch, Jens; Fullstone, Gavin; Tian, Xiaohe; Azizi, Juzaili; Preston, Jane; Volpe, Giorgio; Battaglia, Giuseppe

2017-08-01

In recent years, scientists have created artificial microscopic and nanoscopic self-propelling particles, often referred to as nano- or microswimmers, capable of mimicking biological locomotion and taxis. This active diffusion enables the engineering of complex operations that so far have not been possible at the micro- and nanoscale. One of the most promising tasks is the ability to engineer nanocarriers that can autonomously navigate within tissues and organs, accessing nearly every site of the human body guided by endogenous chemical gradients. We report a fully synthetic, organic, nanoscopic system that exhibits attractive chemotaxis driven by enzymatic conversion of glucose. We achieve this by encapsulating glucose oxidase alone or in combination with catalase into nanoscopic and biocompatible asymmetric polymer vesicles (known as polymersomes). We show that these vesicles self-propel in response to an external gradient of glucose by inducing a slip velocity on their surface, which makes them move in an extremely sensitive way toward higher-concentration regions. We finally demonstrate that the chemotactic behavior of these nanoswimmers, in combination with LRP-1 (low-density lipoprotein receptor-related protein 1) targeting, enables a fourfold increase in penetration to the brain compared to nonchemotactic systems.

Chemotactic synthetic vesicles: Design and applications in blood-brain barrier crossing

PubMed Central

Joseph, Adrian; Contini, Claudia; Cecchin, Denis; Nyberg, Sophie; Ruiz-Perez, Lorena; Gaitzsch, Jens; Fullstone, Gavin; Tian, Xiaohe; Azizi, Juzaili; Preston, Jane; Volpe, Giorgio; Battaglia, Giuseppe

2017-01-01

In recent years, scientists have created artificial microscopic and nanoscopic self-propelling particles, often referred to as nano- or microswimmers, capable of mimicking biological locomotion and taxis. This active diffusion enables the engineering of complex operations that so far have not been possible at the micro- and nanoscale. One of the most promising tasks is the ability to engineer nanocarriers that can autonomously navigate within tissues and organs, accessing nearly every site of the human body guided by endogenous chemical gradients. We report a fully synthetic, organic, nanoscopic system that exhibits attractive chemotaxis driven by enzymatic conversion of glucose. We achieve this by encapsulating glucose oxidase alone or in combination with catalase into nanoscopic and biocompatible asymmetric polymer vesicles (known as polymersomes). We show that these vesicles self-propel in response to an external gradient of glucose by inducing a slip velocity on their surface, which makes them move in an extremely sensitive way toward higher-concentration regions. We finally demonstrate that the chemotactic behavior of these nanoswimmers, in combination with LRP-1 (low-density lipoprotein receptor–related protein 1) targeting, enables a fourfold increase in penetration to the brain compared to nonchemotactic systems. PMID:28782037

Ultimate computing. Biomolecular consciousness and nano Technology

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

Hameroff, S.R.

1987-01-01

The book advances the premise that the cytoskeleton is the cell's nervous system, the biological controller/computer. If indeed cytoskeletal dynamics in the nanoscale (billionth meter, billionth second) are the texture of intracellular information processing, emerging ''NanoTechnologies'' (scanning tunneling microscopy, Feynman machines, von Neumann replicators, etc.) should enable direct monitoring, decoding and interfacing between biological and technological information devices. This in turn could result in important biomedical applications and perhaps a merger of mind and machine: Ultimate Computing.

Multi-scale Observation of Biological Interactions of Nanocarriers: from Nano to Macro

PubMed Central

Jin, Su-Eon; Bae, Jin Woo; Hong, Seungpyo

2010-01-01

Microscopic observations have played a key role in recent advancements in nanotechnology-based biomedical sciences. In particular, multi-scale observation is necessary to fully understand the nano-bio interfaces where a large amount of unprecedented phenomena have been reported. This review describes how to address the physicochemical and biological interactions of nanocarriers within the biological environments using microscopic tools. The imaging techniques are categorized based on the size scale of detection. For observation of the nano-scale biological interactions of nanocarriers, we discuss atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). For the micro to macro-scale (in vitro and in vivo) observation, we focus on confocal laser scanning microscopy (CLSM) as well as in vivo imaging systems such as magnetic resonance imaging (MRI), superconducting quantum interference devices (SQUIDs), and IVIS®. Additionally, recently developed combined techniques such as AFM-CLSM, correlative Light and Electron Microscopy (CLEM), and SEM-spectroscopy are also discussed. In this review, we describe how each technique helps elucidate certain physicochemical and biological activities of nanocarriers such as dendrimers, polymers, liposomes, and polymeric/inorganic nanoparticles, thus providing a toolbox for bioengineers, pharmaceutical scientists, biologists, and research clinicians. PMID:20232368

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