Christina Agapakis is a postdoctoral researcher in the Department of Molecular, Cell, and Developmental Biology at UCLA interested in the structure, evolution, and design of microbial communities. Working with programs like Synthetic Aesthetics and the UCLA Art|Science Center, her research is collaborative and multidisciplinary, exploring the role of art and design in biological engineering and the microbial ecology of soil, skin, and cheese.
In addition to research and teaching in biological design, she blogs about synthetic biology’s history and future for Scientific American.
“Ultimately, the rate limiting factor for the future development of synthetic biology may actually be human creativity.”
-David Drubin et al. “Designing Biological Systems.”
Synthetic biology is often defined as the application of engineering principles to biology. Such a practice is intended to facilitate the future design of biological systems for a range of applications in the production of fuels, foods, materials, and medicines. Within this paradigm, designs of genetic systems built from modular parts start as prototypes (from the Greek πρωτος –“first” and τυπος –“impression”): simplified models meant to interrogate the value of such an approach and provide measurements and tools for the refinement of future engineered systems. But such prototypes also act as provocations, asking us to imagine a future where anything can be built with biology. The work of artists and designers exploring the potential of synthetic biology take such provocations further, creating scientific fictions in the form of narratives, objects, and films rather than the concluding sentences of journal articles. These design fictions question the role new biotechnologies will play in industries and in our everyday lives, imagining changes in the ways that we interact with our bodies and health as well as with consumer products, our homes, and our cities. These prototypes and provocations–by engineers and scientists or by artists and designers–can capture the imagination of wide audiences, influencing the design of new gene networks, the curation of gallery exhibitions, the founding, funding, and regulation of research institutions and startup companies, and existential fears about the hubris of attempting to control nature. In this talk I will use several examples of recent projects from artists and scientists to explore how creativity, narrative, the media, and provocative objects inspire the future of synthetic biologies.
Jim Ajioka is in the Dept. of Pathology at University of Cambridge. His research interests include the investigation of host-parasite interactions using Toxoplasma gondii as a model parasite and the construction of a whole-cell arsenic biosensor for use in the field. Functional genomic methods are used to understand how the parasite alters host signaling pathways for intracellular survival and replication.
A whole cell arsenic biosensor is being constructed to assess and map arsenic contamination of drinking water in South Asia. A disabled strain of Bacillus subtilis is being constructed as the chassis and a the arsenic operon used as the basis for construction of the arsenic sensing circuit. A range of signal amplifiers and pigment outputs are being tested and characterised to provide sensitivity at specific levels of arsenic.
Arkin is Division Director of the Physical Biosciences Division at the Lawrence Berkeley National Laboratory and a Full Professor in the Department of Bioengineering, U.C. Berkeley. He is Director of the Synthetic Biology Institute launched this year at Berkeley and Co-Director of the BIOFAB: International Open Facility Advancing Biotechnology (BIOFAB).
In addition, he directs the Joint Bioenergy Institute’s Bioinformatics Group and Berkeley Lab’s Virtual Institute of Microbial Stress. He is a Professor of Bioengineering at the University of California (UC), Berkeley and was an investigator with the Howard Hughes Medical Institute (HHMI) until 2007. Prof. Arkin has served on many academic and government committees including the US Air Force Science Advisory Board and the Defense Science Study Group.
The thrust of Arkin’s research has focused on developing the physical theory, computational tools and experimental approaches for understanding cellular processes.
Dr. Baldwin is a Reader in Biochemistry at Imperial College London. He has spent his career at the interface of the physical and life sciences, having done an undergraduate degree in Chemistry, he then moved into biochemistry for his PhD working on DNA-protein interactions.
Dr. Baldwin has continued to cross boundaries with other disciplines and more recently his interests have led him to engineering in the field of synthetic biology. He has been one of the advisors of the very successful Imperial College iGEM teams over the last few years. He has also been responsible for developing the training pipeline of synthetic biologists at Imperial College, having established the final year undergraduate module that is taught across the Life Science and Bioengineering Departments, and is Director of the MRes in Systems and Synthetic biology.
He has an active programme of research in DNA assembly, part characterisation and in vivo approaches to directed evolution for the creation of new bioparts.
Travis Bayer is a member of the faculty at Imperial College London where his group works in metabolic engineering, biocatalysis, and synthetic biology. The Bayer group is interested in understanding the evolution of metabolism and genetic regulation, interfacing living and non-living systems, and using biological technologies to enhance global health and sustainability.
Travis received a BS in Molecular Biology from the University of Texas at Austin, a PhD in Biochemistry from the California Institute of Technology, and was a postdoctoral scholar at the University of California, San Francisco before starting his group at Imperial in 2010. Travis has strong industrial collaborations and sits on the scientific advisory boards of synthetic biology startup companies.
Microbial fermentation has been exploited by humans for millenia for the production of food, fuel, and chemicals. Despite intense research efforts, the spectrum of compounds produced in this way is still limited to either naturally occuring fermentative pathways or shows low yields due to genetic regulatory contraints imposed by the host strain. I will discuss our efforts in designing synthetic metabolism and rewiring regulatory architectures in microbial cells to allow high yield production of compounds. As an exemplar, we have engineered a synthetic pathway to the plant hormone strigolactone as a step towards improving crop yield. The parasitic weed species of the Striga genus are among the major biotic stresses on crop yield in Africa, affecting staples such as maize, sorghum, rice, and cowpea. Striga seeds lie dormant in soil until they detect the plant hormone strigolactone, which induces seed germination and attachment of the weed to host roots. The application of strigolactone to farmland before planting can induce ‘suicidal’ germination of Striga seeds. However, the high cost of chemical synthesis of strigolactone has precluded the use of this strategy in the field. The low cost, microbial production of strigolactone can be used in a program of Striga eradication from arable land in Africa.
Wiebe E. Bijker is professor of Technology & Society at Maastricht University, The Netherlands. He was trained as a physicist and engineer (Delft), studied philosophy (Groningen) and has a PhD in sociology and history of technology (Twente). The volume “Social Construction of Technology” (1987, 2012), which he co-edited with Pinch and Hughes, was selected by the MIT staff as one of the 30 most influential books ever published by MIT Press.
His current research relates to questions about science and technology for development, ranging from nanotechnology to handloom weaving and from the vulnerability of technological cultures to integrating indogenous forms of knowledge into university teaching. Bijker is past president of the Society for Social Studies of Science; chairman of the Board of the Research Council “WOTRO””Science for Global Development”; member of the Board of the Rathenau Institute (the Dutch Technology Assessment Office); and member of the Health Council of the Netherlands. For more details, see: www.fdcw.unimaas.nl/staff/bijker.
All technologies are designed, and so are the products of synthetic biology. Designers make crucial choices that result in values being incorporated in technology, and which have implications for technology’s role in society. Since all designs are thus inevitably value-laden, Bijker will propose that we explicitly address this question of implicit values and social and political choices in designing technologies in general, and in synthetic biology in particular. He will argue that societies need to experiment with new ways of democratically dealing with emerging technologies (like synthetic biology), and will illustrate this with the societal dialogue in The Netherlands on nanotechnology (2009-2011).
Jane Calvert is a Reader in Science, Technology and Innovation Studies at the University of Edinburgh. She is particularly interested in the social dimensions of synthetic biology, including the role of social scientists in the field, attempts to make biology into an engineering discipline, and intellectual property and open source. Jane is part of the interdisciplinary EPSRC/NSF ‘Synthetic Aesthetics’ project, which brings together synthetic biology, social science, art and design.
She was a member of the Royal Academy of Engineering’s Working Party on Synthetic Biology, and the UK Synthetic Biology Roadmap Coordination Group. She is currently a member of the Nuffield Council of Bioethics Working Party on Emerging Biotechnologies, the Hastings Center Working Group on Ethical Issues in Synthetic Biology, and the BBSRC’s Bioscience and Society Panel.
Dr. Matthew Chang is an assistant professor of the School of Chemical and Biomedical Engineering at Nanyang Technological University (NTU) in Singapore. He received Ph.D. from the University of Maryland, USA, and B.S. from Seoul National University, Korea. His honors include the Scientific and Technological Achievement Award from U.S. Environmental Protection Agency.
Dr. Chang has published over 50 research articles in the fields of biochemical engineering and synthetic biology. His primary research interests are in the development of synthetic microbes for engineering applications.
Synthetic biology aims to engineer genetically modified biological systems that perform novel functions that do not exist in nature, with reusable, standard interchangeable biological parts. The use of these standard biological parts enables the exploitation of common engineering principles such as standardization, decoupling, and abstraction for synthetic biology. With this engineering framework in place, synthetic biology has the potential to make the construction of novel biological systems a predictable, reliable, systematic process. While the development of most biological systems remains largely ad hoc, recent efforts to implement an engineering framework in synthetic biology have provided long-awaited evidences that engineering principles can facilitate the construction of novel biological systems. In this talk, our recent efforts to develop therapeutic microbes with programmable functionalities will be presented. In particular, an emphasis will be placed on our development of synthetic probiotics, equipped with clinically relevant functionalities such as pathogen detection, antimicrobial molecule release, directed movement, and biofilm reduction, that showed effective antimicrobial activities against target human pathogens in in vitro and eukaryotic infection models. This development suggests the possibility that probiotics could potentially be engineered for prevention and treatment of target infectious diseases, which may provide an antimicrobial strategy that is complementary to current antibiotic therapies.
Jason Chin is a Programme Leader at the Medical Research Council Laboratory of Molecular Biology (MRC-LMB), where he is also Head of the Centre for Chemical & Synthetic Biology (CCSB). He is joint appointed at the University of Cambridge Department of Chemistry & is a fellow and director of studies in Natural Sciences at Trinity College. Jason was an undergraduate at Oxford with John Sutherland, obtained his PhD as a Fulbright grantee from Yale with Alanna Schepartz, and was a Damon Runyon Fellow at Scripps with Peter Schultz.
He became an EMBO Young Investigator in 2005 and a tenured group leader in 2007. He was awarded the Francis Crick Prize by the Royal Society and the Royal Society of Chemistry’s Corday Morgan Prize. He was also awarded the EMBO Gold Medal and elected to EMBO membership in 2010. He is the inaugural recipient of the Louis-Jeantet Young Investigator Career Award.
The information for synthesizing the molecules that allow organisms to survive and replicate is encoded in genomic DNA. In the cell, DNA is copied to messenger RNA, and triplet codons (64) in the messenger RNA are decoded – in the process of translation – to synthesize polymers of the natural 20 amino acids. This process (DNA RNA protein) describes the central dogma of molecular biology and is conserved in terrestrial life. We are interested in re-writing the central dogma to create organisms that synthesize proteins containing unnatural amino acids and polymers composed of monomer building blocks beyond the 20 natural amino acids. I will discuss our invention and synthetic evolution of new ‘orthogonal’ translational components (including ribosomes and aminoacyl- tRNA synthetases) to address the major challenges in re-writing the central dogma of biology. I will discuss the application of the approaches we have developed for incorporating unnatural amino acids into proteins and investigating and synthetically controlling diverse biological processes, with a particular emphasis on understanding the role of post-translational modifications.
King L Chow
King Chow is Professor of Life Science and Biomedical Engineering at the Hong Kong University of Science and Technology. He holds the positions of Associate Dean of Students, Academic Director of the Common Core Program, Director of the Molecular Biomedical Sciences Program and Associate Director of the Bioengineering Program at HKUST.
His research focuses on molecular genetics, neural development and evolutionary biology. He first brought synthetic biology to Hong Kong through organizing the SB4.0 in 2008. He led the iGEM Asia regional competition in the year 2011 and 2012, and advised the HKUST teams for the past five years. He is active in teaching broad areas in life science disciplines and general science education at undergraduate and postgraduate level, earning him the School of Science Teaching Award and the Michael G. Gale Medal of distinguished teaching at HKUST.
Lionel Clarke, as Team Leader, Biodomain and Open Innovation, is engaged in the planning and delivery of strategic research programmes to Shell across the “Biodomain” (“Biofuels and other biotechnology applications”), deploying internal and external resources — including academic and industrial partnerships. He is based at the Shell Technology Centre Thornton, UK.
His extensive experience in Shell taking innovative ideas for better fuels from laboratory to market ranges from the worldwide replacement of leaded gasoline to the introduction of cleaner, improved performance fuels. His considerable expertise and interest in advanced bio-fuels stems from early first-hand experience designing fuels for Brazil. Prior to joining Shell, he studied at Imperial College, followed by research fellowships at the Cavendish Laboratory Cambridge and Grenoble. He chaired the UK Synthetic Biology Roadmap coordination group during 2012 and is now co-Chairman of the UK Synthetic Biology Leadership Council.
James J. Collins is an Investigator of the Howard Hughes Medical Institute, and a William F. Warren Distinguished Professor, University Professor, Professor of Biomedical Engineering, Professor of Medicine and Director of the Center for Synthetic Biology at Boston University. He is also a core founding faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard University.
His research group works in synthetic biology and systems biology, with a particular focus on using network biology approaches to study antibiotic action, bacterial defense mechanisms, and the emergence of resistance. He has received numerous awards and honors, including a Rhodes Scholarship, a MacArthur “Genius” Award, an NIH Director’s Pioneer Award, a Sanofi-Institut Pasteur Award, as well as several teaching awards.
Professor Collins is an elected member of the National Academy of Engineering, the Institute of Medicine, and the American Academy of Arts & Sciences, and a charter fellow of the National Academy of Inventors.
Synthetic biology is bringing together engineers and biologists to design and construct biological circuits out of proteins, genes and other bits of DNA, and to use these circuits to rewire and reprogram organisms. These re-engineered organisms are going to change our lives in the coming years, leading to cheaper drugs, “green” means to fuel our car and clean our environment, and targeted therapies to attack “superbugs” and diseases such as cancer. In this talk, we highlight recent efforts to create synthetic gene networks and programmable cells, and discuss a variety of synthetic biology applications in biomedicine, with a particular focus on infectious diseases.
Dr. Junbiao Dai received his Bachelors of Science from Nanjing University in 1993. He received his Master of Science in Biology in 2000 from Tsinghua Univeristy and his PhD in Molecular, Cellular and Developmental Biology in 2006 from Iowa State University. After receiving his PhD he was a post-doctoral fellow at the Johns Hopkins University School of Medicine. He is currently an Associate Professor in School of Life Sciences at Tsinghua University.
His research interests lie in genetics, genomics and system biology using budding yeast as a model system, with emphasis on histone modifications, chromatin biology and synthetic biology. He’s one of the key members in synthetic yeast consortium and leading a team to synthesize the largest yeast chromosome, chromosome XII.
Recent advances in DNA synthesis technology have enabled the construction of not only the genetic circuits or pathways, but also the entire genome in an organism, leading to the new era of genome engineering. To further our understanding of the eukaryotic genome, an international synthetic yeast genome project, Sc2.0 was initiated. Work on 8 of the 16 Sc2.0 chromosomes has been begun by teams in the U.S., China and the U.K. Among the yeast chromosomes, Chr XII is the largest one, which contains about one million base pairs of DNA plus more than 100 copies of the 9.1kb ribosome DNA (rDNA) repeat. Here we describe our strategies to synthesize this giant chromosome. To facilitate the assembly of the synthetic chromosome, we explore the “awesome power” of homologous recombination in budding yeast. Instead of synthesizing the mega-chunks as designed before, we developed an over-lapping integration strategy. In addition, laborious DNA extraction/cloning procedures were substituted by new “one pot” in vitro assembly method, leading to the fast and efficient replacement of the endogenous chromosome. Furthermore, we will discuss multiple designs applied to the rDNA repeats, trying to further our understanding of this specific DNA region.
Lord Ara Darzi
Professor the Lord Darzi of Denham PC, KBE, FMedSci, HonFREng
Lord Darzi holds the Paul Hamlyn Chair of Surgery at Imperial College and is an Honorary Consultant Surgeon at the Imperial College Healthcare NHS Trust and the Royal Marsden NHS Trust Hospitals. In October 2010 he was appointed as Director for the Institute of Global Health Innovation at Imperial College. In 2012 Lord Darzi took up the role of Chair, Imperial College Health Partners.
He was knighted for his services in medicine and surgery in 2002. Lord Darzi was introduced to the United Kingdom’s House of Lords in 2007 as Professor the Lord Darzi of Denham and appointed Parliamentary Under-Secretary of State at the Department of Health. He relinquished this role in July 2009. Under appointment (July 2009 – March 2013) as United Kingdom’s Global Ambassador for Health and Life Sciences Lord Darzi took an active international role in outlining and shaping healthcare policy. Lord Darzi was appointed as a member of Her Majesty’s Most Honourable Privy Council in June 2009. Recently, Lord Darzi was elected as Fellow of the Royal Society.
Innovation has delivered incalculable benefits to billions of people. But the demands of this century will require even greater change because many health systems are rapidly becoming unsustainable. Not only does the non-communicable disease epidemic threaten to overwhelm health services. The costs of care are also rising, and this at a time when many countries face perhaps a decade of fiscal consolidation. In his talk, Professor Darzi will discuss these drivers of innovation, arguing that more of the same will not be enough to restore health systems’ sustainability: fundamentally new ways of delivering care will need to be found that are at once better and cheaper. Although this is clearly a challenge that has not yet been met, Professor Darzi will point to innovations from the emerging world with the potential to reshape health services in developed countries. A key part of the answer will be to close the gap between what we know and what we do—and focus on the uptake of innovations every bit as much as on the basic research which gives rise to them.
Engineering and Physical Sciences Research Council (EPSRC)
Victor de Lorenzo
Victor de Lorenzo is a Spanish Chemist and Microbiologist. He works at the National Centre of Biotechnology (CNB-CSIC) in Madrid, where he is employed since 1996 after successive postdocs at the University of California (Berkeley), the University of Geneva and the Federal Center of Biotechnology (Braunschweig).
His research exploits advanced molecular biology and genetic engineering of microorganisms for the sake of biomonitoring, bioremediation – and wherever possible, valorization of chemical pollution in the Environment. He is a member of the European Molecular Biology Organisation (EMBO), the American Academy of Microbiology (AAM) and the European Academy of Microbiology (EAM).
One of his longstanding interests is the development of standardized molecular tools for deep genetic and genomic refactoring of Gram-negative microorganisms, in particular Pseudomonas putida. He is currently trying to develop an all-prokaryotic artificial immune system based on parts and devices mined from environmental bacteria.
The prokaryotic world is the largest reservoir of enzymatic activities in the Biosphere, but the vast majority of this treasure trove has not yet been exploited. To overcome this state of affairs new conceptual and material tools, as well as understanding of a large number of fundamental biological processes (e. g. metabolism) are required. Key aspects include optimization of a limited number of genomic and biochemical chasses compatible with environmental applications, standardization of methods of physical assembly of DNA constructs, development of genetic tools for deployment and stable maintenance of the implanted traits and adjustment of the engineered property to the genetic and biochemical background of the host. In this context, we have developed a large number of molecular tools for designing strains of the soil bacterium Pseudomonas putida aimed at biosensing and / or biodegradation of recalcitrant chemicals that are environmental pollutants. This multi-tiered effort involves [i] editing and streamlining of the existing genome for deletion of non-desirable segments (eg prophages) and enhancement of beneficial functions (eg stress tolerance), [ii] adoption of the so called Standard European Vector Architecture (SEVA) format for analysis, construction and deployment of genetic constructs in Gram-negative bacteria other than E. coli and [iii] development of fusion partners for targeting expression of given proteins to various cell compartments. The value of such standards (as well as their shortcomings) will be exemplified in our efforts to biodegrade anaerobically the environmental pollutants 1,3-dichloroprop-1-ene with a heavily engineered P. putida strain.
Domitilla Del Vecchio
Domitilla Del Vecchio received the Ph. D. degree in Control and Dynamical Systems from CalTech, Pasadena, and the Laurea degree in Electrical Engineering from the University of Rome at Tor Vergata in 2005 and 1999, respectively. From 2006 to 2010, she was an Assistant Professor in the Department of Electrical Engineering and Computer Science and in the Center for Computational Medicine and Bioinformatics at the University of Michigan, Ann Arbor.
In 2010, she joined the Department of Mechanical Engineering and the Laboratory for Information and Decision Systems (LIDS) at the Massachusetts Institute of Technology (MIT), where she is currently the W. M. Keck Career Development Associate Professor in Biomedical Engineering. She is a recipient of the Donald P. Eckman Award from the American Automatic Control Council (2010), the NSF Career Award (2007), the Crosby Award, University of Michigan (2007), the American Control Conference Best Student Paper Award (2004), and the Bank of Italy Fellowship (2000).
The ability to accurately predict a network’s behavior from that of the composing modules is a major challenge in systems and synthetic biology due to individual modules exhibiting context-dependent behavior. One leading cause of context-dependence is retroactivity, a phenomenon similar to loading that affects the dynamic performance of a module upon connection to other modules. Retroactivity is particularly daunting for synthetic biology, in which working modules often fail to function as predicted once interacting with each other. Here, we illustrate analysis and design techniques to mitigate this problem along with experimental demonstrations. First, we introduce a simple analysis framework, conceptually analogous to Thevenin’s electrical circuit theory, which accounts for retroactivity to quantitatively predict how a module’s behavior will change after interconnection with other systems. Experiments carried both in yeast and E. coli validate this theory and demonstrate that retroactivity substantially deteriorates the dynamic response of gene circuits. To solve this problem, we introduce a load driver device to connect a circuit to a variable number of systems (load) in such a way that the circuit output is reliably transmitted to the load while preserving the unloaded system performance. The load driver design is based on fast regulatory elements that reach quasi-steady state quickly in response to slow changing inputs (principle of time-scale separation). These fast elements are in sufficiently high concentrations such that the quasi-steady state is unaffected by load. We built and experimentally tested in Saccharomyces cerevisae an instance of a load driver with circuitry based on (fast) phosphotransfer reactions. We first built and tested several transcriptional regulatory networks and demonstrated that their responses were severely impaired due to load. We then demonstrated that incorporation of our load driver restored response dynamics, thus remedying the load problem.
Douglas Densmore received his Ph.D. in electrical engineering from the University of California, Berkeley. He worked as a postdoctoral research fellow at SynBERC and the Joint BioEnergy Institute.
Densmore’s research centers on extracting design techniques from electronic design automation and applying them to the design of synthetic biological systems. The Clotho unified tool set – a two-time winner of the “best software tool” at the International Genetically Engineered Machines Competition – captures many of these research concepts. He received the National Science Foundation’s CAREER Award and the ECE Award for Excellence in Teaching at BU, and he is currently a junior faculty fellow in the Hariri Institute for Computing and Computational Science and Engineering at BU. He is also the co-founder and president of the Nona Research Foundation for open source synthetic biology software.
In this talk, I will outline an example of how starting with a high level specification of a desired synthetic genetic circuit, a fully realized DNA sequence can be produced with minimum human interaction in an academic environment. Key to this process is the formalized expression of primitive building blocks, functional equivalence, assembly plan optimization, data persistence, and liquid handling protocol generation. In addition, I will hypothesize on how this process can be scaled to industrial settings and outline the current software ecosystems I see emerging in the field.
Tom Ellis is a lecturer (Assistant Professor) in the Department of Bioengineering at Imperial College London and leads the Ellis Lab at the Centre for Synthetic Biology and Innovation (CSynBI). His research focuses on developing the tools and methods to rewire gene expression and to enable the future design and assembly of synthetic microbial genomes. This research is being utilised in CSynBI on projects on intrinsic containment and for biofuel and antibiotic biosynthesis.
Ellis was an undergraduate at Oxford University and received his PhD from the University of Cambridge. Following two years in commercial drug discovery, he was a postdoctoral fellow with James J Collins at Boston University. At Imperial College, he leads the UK contribution to the Sc2.0 Synthetic Yeast genome project and co-organises undergraduate synthetic biology teaching.
As we construct the first synthetic eukaryotic genome with the Sc2.0 consortium, how do we plan to add new functions to the minimal genomes that are created? While much larger, our own genome contains less than 23,000 genes, yet it encodes for many of the most complex systems we know. The key to this immense complexity is gene regulation, and recent work has estimated that the human genome contains nearly 4 million switches that control where and when the genes are turned on and off in a myriad of ways. Engineering composable switches is the key to bringing designed complexity to synthetic biology. To do this we are taking a bottom-up approach; using bioinformatics tools to first identify minimal promoter sequences and then using these as the framework to rationally engineer dozens of new synthetic switches. Starting in S. cerevisiae, we have developed a workflow to rapidly generate promoter libraries during the process of DNA assembly. Mutation then guides where we target these promoters with a combinatorial TAL-Effector library that offers 1-to-1 repression of the intended gene. Wiring these synthetic switches together in increasingly large constructs enables us to understand the current limiting factors for engineering complexity – orthogonality, noise, burden and genetic instability – and guides us to generate new designs that account for these factors.
Director, International Liaison Office
Office of Naval Research, Global
Professor Paul Freemont is co-founder and co-director of the EPSRC Centre for Synthetic Biology and Innovation at Imperial College London. The Centre is the first of its kind in the UK and aims to develop an foundational technologies to enable synthetic biology research in application areas like biosensors, bioprocessing, metabolic and genome engineering. Previous to this he was head of the Division of Molecular Biosciences, and head of the Centre for Structural Biology having joined Imperial from Cancer Research UK London Research Institute where he was a Principal Scientist and director of the Macromolecular Structure and Function laboratory.
His research interests focuses on understanding the molecular mechanisms of macromolecular assemblies associated with human disease and is author of over 150 peer-reviewed scientific publications. His research in synthetic biology focuses on in vitro foundational technologies and biosensing. He is co-founder of a spin out company Equinox Pharma Ltd and holds a number of external positions including chair of the Diamond Light Source Scientific Advisory Committee and member MRC Molecular and Cellular Medicines Board.
Emma Frow is a Lecturer in Science & Technology Studies at the University of Edinburgh, and Associate Director of the ESRC Genomics Policy & Research Forum. She is a sociologist of science, and one of her core research interests relates to how standards are developed and used as tools of governance in contemporary biosciences.
Emma is a Principal Investigator for the European Commission ST-FLOW project on standardization in synthetic biology, and a researcher in the UK Flowers Consortium concerned with developing infrastructure for synthetic biology. Emma was also a coordinator of the UK Synthetic Biology Standards Network from 2008-2011, and has been a Human Practices advisor and judge for the iGEM competition since 2008. Originally trained as a bioscientist, she has a PhD in biochemistry from the University of Cambridge, and worked at Nature before moving up to Edinburgh in 2006.
Standardization is a key principle being brought from engineering into the field of synthetic biology. Within the synthetic biology community there are several ongoing attempts to develop and implement standards, according to a range of different typologies. In this talk I want to take a step back and focus on some key characteristics of standards, and the roles they play in our daily lives as researchers, policymakers, and citizens. Drawing on examples from within and outside synthetic biology, I will show how standards are fundamentally both technical and social instruments that bridge the worlds of things and people. As well as being important technical instruments for achieving reliability, predictability and control in engineered systems, standards are also associated with social and political institutions of power, accountability, credibility, and trust. Indeed, standardization has become a key form of governance in modern societies, and its implications reach far beyond laboratory practice. During their development, standards require a theory or imagination of how they will be used; in their implementation, standards are necessarily always partial, vulnerable to resistance, and open to revision. These characteristics have implications for how the synthetic biology community chooses to approach practices of standardization – what kinds of values might we strive to build into standards for synthetic biology (technical standards, safety standards, ownership standards, and so on) that could help to promote ‘biotechnology in the public interest’? And whose expertise should be involved to develop standards that are effective and equitable?
Martin Fussenegger is Professor of Biotechnology and Bioengineering at the Department of Biosystems Science and Engineering (D-BSSE) of ETH Zurich and at the University of Basel. He graduated with Werner Arber at the Biocenter of the University of Basel (1992), obtained his Ph.D. in Medical Microbiology (1994) at the Max Planck Institute of Biology and continued his postdoctoral studies on host-pathogen interactions at the Max Planck Institute of Infection Biology.
He joined the ETH Institute of Biotechnology (1996), and received his habilitation in 2000, and became Swiss National Science Foundation Professor of Molecular Biotechnology in 2002, prior to being awarded a Chair in Biotechnology and Bioengineering at the ETH Institute for Chemical and Bioengineering in 2004. On a presidential mission, he moved to Basel in 2008 to build up the D-BSSE. He is a fellow of the American Institute for Medical and Biological Engineering and member of Swiss Academy of Engineering Sciences.
Michele S. Garfinkel is the Manager of the Science Policy Programme at the European Molecular Biology Organization in Heidelberg, Germany. Her work focuses on societal concerns for the introduction of new biological technologies, scientific publishing, and the responsible conduct of research.
Previously she was a policy analyst at the J. Craig Venter Institute, where she worked on societal issues related to the emerging technologies of genomics, particularly synthetic biology. She has also done policy research as a staff member at the American Association for the Advancement of Science, primarily on human stem cell research policy. As a research fellow at Columbia University’s Center for Science, Policy & Outcomes she worked on biomedical research policy.
Michele holds an AB in Genetics from the University of California, a PhD in Microbiology from the University of Washington, and an MA in Science, Technology, and Public Policy from the George Washington University.
Alexandra Daisy Ginsberg
Alexandra Daisy Ginsberg is an artist, designer and writer, exploring the implications of emerging technologies, and seeking new roles for design. As Design Fellow on Synthetic Aesthetics (Stanford University/University of Edinburgh), she has curated an international project investigating the ‘design of nature’, developing novel modes of collaboration and critical discourse between art, design and synthetic biology. The project will be published in 2014 by MIT Press.
Daisy studied Architecture at the University of Cambridge (MA), design at Harvard University and MA Design Interactions at the Royal College of Art, London. Her work has been exhibited and published internationally, including MoMA New York, the Art Institute of Chicago, the Israel Museum and the National Museum of China. Daisy publishes, teaches and lectures internationally.
In 2011, her collaborative work E.chromi was nominated for Designs of The Year and Index Awards, and she won the World Technology Award for Design. Daisy received the first London Design Medal for Emerging Talent in 2012.
As Director Operations for Synthetic Biology, Marcus Graf is responsible for the entire production of synthetic genes in Regensburg, Germany including all downstream services and biosecurity and biosafety compliance. This incorporates the ISO 9001:2008 certified processes of design, the syntheses and the quality control of genes, gene libraries and expression vectors as well as plasmid DNA production.
As cofounder of the previous GENEART AG, now fully owned by Lifetechnologies Inc, Marcus Graf achieved a double digit volume growth year over year in gene synthesis reaching more than 5.0M basepairs per month in output. He is also a founding member of the International Gene Synthesis Consortium (IGSC) that strives to set and constantly improve biosecurity standards of the gene synthesis industry. The ICGS companies together represent more than 80% of commercial gene synthesis capacity world-wide.
Gene synthesis at increasing scale is a foundational suite of technologies and capabilities, advancing diverse research and industrial applications in synthetic biology engineering of living systems. Gene synthesis is a typical “dual-use” technology, simultaneously applicable for greater good and fulfillment of the promise of synthetic biology while potentially misused or intentionally designed for nefarious purposes. As current national and global guidelines, regulations or oversight are either in early development or don’t yet exist, awareness among community stakeholders regarding dual-use issues and the related need for effective biosecurity protocols is high. The leading synthetic gene providers proactively formed the IGSC in 2009, developing and implementing “The Harmonized Protocol”, a common parameter set for sequence homology-based gene order screening and customer information analysis among IGSC member companies. The Harmonized Protocol was in large part mirrored in the development of the Screening Framework Guidance for Providers of Synthetic Double-Stranded DNAb published in 2010. Since this time, membership in the IGSC has grown and the consortium enjoys continued regular engagement and collaboration among its members and with regulatory, policy, enforcement and academic stakeholders across and beyond the synthetic biology community. The common tools and implemented biosecurity screening processes used by the IGSC for compliance with national law, including export control regulations and international guidelines will be described. Development and implementation of a common and shared biosecurity sequence database and flag alert system operating in the context of member companies’ order process and supporting decision guidance by safety officers and informaticians to effectively resolve a concern sequence order or customer profile will be presented.
Matthew Harsh is an Assistant Professor in the Centre for Engineering in Society at Concordia University in Montreal. He holds a BSc in Materials Science and Engineering from Northwestern University. As a Marshall Scholar, he earned an MSc and PhD in Science and Technology Studies from the University of Edinburgh.
Much of his research is about how new and emerging technologies can improve livelihoods in Africa. His current research topics include: civil society involvement in policy making for genetically-modified crops in Kenya; equity implications of nanotechnology applications for water, energy and agri-food in South Africa; engineering education and social entrepreneurship in developing countries; and the affects of political unrest on research and education in Kenya.
He is Senior Producer of ‘Brother Time’, a documentary about political unrest after the 2007 Kenyan election. His work can be found in the Journal of International Development, Science and Public Policy, and Development and Change.
Given growing food insecurity, countries in sub-Saharan Africa are increasingly using advanced biotechnologies and genetic modification to develop new crops. Innovation surrounding new and emerging biotechnologies is complicated not only because of technical capacities, but also because of the diversity of organizations and institutions involved with different priorities and strategies. Using a systems of innovation approach, this presentation analyzes several agricultural biotechnology projects in Kenya. It demonstrates that while these projects have facilitated new connections between organizations and new knowledge pathways critical to innovation, the projects result in innovation for its own sake – valuing the process of innovation over the intended benefits, in this case improved livelihoods of farmers. Researchers, companies and civil society organizations need to partner in new ways in order to better incorporate the needs and values of farmers into biotechnology innovation.
Jim Haseloff is a plant biologist working at the University of Cambridge. His scientific interests are focused on the engineering of plant morphogenesis, using microscopy, molecular genetic, computational and synthetic biology techniques. (see www.haseloff-lab.org) He and his group have developed new approaches to RNA engineering, quantitative imaging and gene expression in plants, and promote the potential of Synthetic Biology as a tool to engineer new feedstocks for sustainable use. (see www.synbio.org.uk)
Synthetic Biology has great potential as a tool for the engineering of multicellular organisms. (1) The greatest diversity of cell types and biochemical specialisation is found in multicellular systems, (2) the molecular basis of cell fate determination is increasingly well understood, and (3) it is feasible to consider creating new tissues or organs with specialized biosynthetic or storage functions by remodelling the distribution of existing cell types. Of all multicellular systems, plants are the obvious first target for this type of approach. Plants possess indeterminate and modular body plans, have a wide spectrum of biosynthetic activities, can be genetically manipulated, and are widely used in crop systems for production of biomass, food, polymers, drugs and fuels.
Current GM crops generally possess new traits conferred by single genes, and expression results in the production of a new metabolic or regulatory activity within the context of normal development. However, cultivated plant varieties often have enlarged flowers, fruit organs or seed, and are morphologically very different from their wild-type ancestors. The next generation of transgenic crops will contain small gene networks that confer self-organizing properties, with the ability to reshape patterns of plant metabolism and growth, and the prospect of producing neomorphic structures suited to bio production.
We have developed a battery of computational, imaging and genetic tools to allow clear visualisation of individual cells inside living plant tissues and have the means to reprogram them. These techniques are well suited to study of simple experimental systems such as the lower plant Marchantia polymorpha and surrogate microbial populations. These types of simple systems are becoming increasingly important to explore the next generation of genetic circuits with self-organising properties.
Philipp Holliger is a program leader at the MRC Laboratory of Molecular Biology (MRC-LMB) in Cambridge, UK. Phil graduated at ETH Zürich with Steve Benner before moving to the Cambridge Centre for Protein Engineering (CPE), for his Ph.D. and postdoctoral fellowship with Sir Greg Winter. In 2000, he joined the MRC-LMB as a tenure-track and was appointed program leader in 2005. His research interests span the fields of chemical biology, synthetic biology and directed evolution.
Synthetic biology seeks to probe fundamental aspects of biological form and function by construction (i.e. resynthesis) rather than deconstruction (analysis). Synthesis thus complements reductionist and analytic studies of life, and allows novel approaches towards fundamental biological questions.
We have been exploiting the synthesis paradigm to explore the chemical etiology of the genetic apparatus shared by all life on earth. Specifically, we ask why information storage and propagation in biological systems is based on just two types of nucleic acids, DNA and RNA. Is the chemistry of life’s genetic system based on chance or necessity? Does it reflect a “frozen accident”, imposed at the origin of life, or are DNA and RNA functionally superior to simple alternatives.
I’ll present progress towards in the synthesis, replication and evolution of such alternative genetic polymers (XNA) . Such synthetic genetic polymers expand the central dogma and conclusively address questions such as the capacity of genetic polymers other than DNA and RNA for information storage, heredity and evolution.
The work also opens up an entirely new field of “synthetic genetics” concerned with exploration of the informational, structural, and catalytic potential of these novel polymers. Synthetic genetics will not only advance our understanding of the parameters and precise chemical logic of molecular information encoding and retrieval but promises to provide a rich source of ligands, catalysts, and nanostructures with tailor-made chemistries for manifold applications ranging from medicine to material science .
Farren Isaacs is Assistant Professor of Molecular, Cellular and Developmental Biology and Systems Biology Institute at Yale University. He received a B.S.E in Bioengineering from the University of Pennsylvania and his Ph.D. from the Biomedical Engineering Department and Bioinformatics Program at Boston University. In his Ph.D., he pioneered the development of synthetic RNA components capable of probing and programming cellular function.
As a research fellow in the Genetics at Harvard, he then invented enabling technologies for genome engineering, including MAGE (Multiplex Automated Genome Engineering) and CAGE (Conjugative Assembly Genome Engineering). His research is focused on developing foundational genomic and cellular engineering technologies with the goal of developing new genetic codes, and engineered cells that serve as factories for chemical, drug and biofuel production.
He has recently been named a “rising young star of science” by Genome Technology Magazine and a Beckman Young Investigator by the Arnold and Mabel Beckman Foundation.
A defining cellular engineering challenge is the development of high-throughput and automated methodologies for precise manipulation of genomes. To address these challenges, we develop methods for versatile genome modification and evolution of cells. Multiplex automated genome engineering (MAGE) simultaneously targets many locations on the chromosome for modification in a single cell or across a population of cells, thus producing combinatorial genomic diversity. Conjugative assembly genome engineering (CAGE) facilitates the large-scale assembly of many modified genomes. Our methods treat the chromosome as both an editable and evolvable template and are capable of fundamentally re-engineering genomes from the nucleotide to the megabase scale. I will present one application of MAGE to generate combinatorial genomic variants from a complex pool of synthetic DNA to diversify target genes in order to optimize biosynthetic pathways. Then, I will also describe the integration of MAGE and CAGE to engineer a Genomically Recoded Organism (GRO), replacing all 321 UAG stop codons with the synonymous UAA stop codon in E. coli. This work increases the toolbox for genomic and cellular engineering with the goal of expanding the functional repertoire of organisms.
Dr. Alfonso Jaramillo, Institute of Systems and Synthetic Biology (France), is a senior research scientist at CNRS and group leader of the Synth-Bio group. He held previously a tenured faculty position at Ecole Polytechnique (the top higher education college in France according to most rankings). He holds a PhD in Theoretical Physics (1999) and a Habilitation in molecular biology (2007).
He directs a microbiology lab (equipped with in house automated microscopy and microfabrication fab) that currently employs 10 researchers. He has published 61 papers and refereed conference proceedings, and he is currently member of several editorial boards. He has participated in 6 EU-funded consortia in Synthetic Biology and he has co-ordinated 2 of them.
The reprogramming of cells with novel behavior involves the engineering of synthetic circuits manipulating of DNA, RNA and/or proteins, which requires targeting nucleic acids with high specificity. RNA is an ideal molecule to be used as molecular interaction domains able to recognize other RNA or DNA. Unfortunately, RNA stability and function depends critically on global interactions, which often prevents a modular design strategy. This is particularly relevant when designing allosteric conformations in the RNA to create switching behavior. Such design could be done using computational methods. For this, we show how using standard secondary structure methods can already produce RNA switches working in E. coli if we incorporate evolutionary computation algorithms. There, we automatically optimize the sequences of a RNA circuit by minimizing their interaction activation and formation energies. Such objective function implements known RNA stability and kissing loop mechanisms. The recent engineering of self-assembly DNA interaction pathways in vitro by computational algorithms could not be extended to RNA in living cells until now. Here we report a general de novo RNA circuit design approach, where we have experimentally validated in E. coli fully synthetic RNAs displaying switching behavior. We also show in E. coli that our riboregulatory devices can be combined with known functional RNA fragments (such as ribozymes and aptamers) to create complex RNA circuits in bacteria. We also characterized their in vivo RNA dynamics by using microfluidics time-lapse microscopy to track single-cells. Our work provides a new paradigm to design functional RNAs circuits by only relying on RNA stability and RNA-RNA interactions.
Roman Jerala Department of Biotechnology @National institute of Chemistry in Ljubljana, Slovenia
BSc and PhD in chemistry (1993), University of Ljubljana, Slovenia postdoc U.Virginia 1994-1995 since 2002 head of Department of biotechnology, NIC since 2009 director of synthetic biology area at Centre of excellence EN-FIST
Research interests: – synthetic biology (iGEM team leader since 2006): mammalian cell engineering, information processing in cells, medical applications, bionanomaterials – molecular mechanisms of innate immunity
Proteins are able to perform versatile functions due to the variability of aminoacid side chains and their tertiary structures that evolved through complex cooperative interactions. De novo protein fold design is still very challenging. We devised a strategy to design self-assembling polypeptide nanostructured polyhedra, based on orthogonal coiled-coil dimerizing mudular segments. We designed end experimentally demonstrated formation of the tetrahedron that self-assembles from a single polypeptide chain comprising 12 concatenated coiled-coil-forming segments connected by flexible peptide hinges. Path of the polypeptide chain is guided by the defined order of segments that traverse each of the 6 edges of the tetrahedron exactly twice, forming coiled-coil dimers with their corresponding partner segments. WE demonstrated formation of discrete particles in agreement with designed shape using CD, DLS, imaing by electron microscopy and AFM. Coincidence of the polypeptide termini in the same vertex was demonstrated by reconstitution of the split fluorescent protein by the polypeptide with the correct tetrahedral topology, while polypeptides with a deleted or scrambled segment order fail to self-assemble correctly. This design platform provides the basis for construction of new topological polypeptide folds based on the set of orthogonal interacting polypeptide segments.
Gyoo Yeol Jung
Gyoo Yeol Jung is an Associate Professor of Department of Chemical Engineering as well as Head of Interdisciplinary School of Bioscience and Bioengineering, POSTECH of Korea. He received his Ph.D. degree from Seoul National University of Korea and did his postdoc research at MIT with professor Greg Stephanopoulos.
His research is focused on Synthetic Biology and Genetic Analysis System. He published a number of papers in the premier journals including Science and Nature Communications. Dr. Jung is an Associate Editor of Biotechnology and Bioprocess Engineering and editor of Electrophoresis and Journal of Biological Engineering.
Metabolic Engineering aims to purposeful design or redesign biological system for the production of commercially valuable chemicals such as biofuels, platform chemicals and biologically active compounds. To achieve the successful design or redesign of the biological systems, robustness of naturally occurring biological systems has to be relieved so that cells can be easily redesigned. Although extremely huge efforts have been made to find genetic target to improve metabolic function of the microorganisms, there still exists the additional room for the non-rational approach. Currently, typical approach for metabolic engineering uses both rational approach as well as non-rational methods such as combinatorial and evolutionary methods. One of the most critical problems of metabolic engineering is especially robustness of the biological systems. Bacterial cells are generally evolved at the various levels from DNA to protein for maintaining their robustness against the changing circumstances. Therefore, general strategy to modify cellular physiology depending the robustness or flexibility of the biological systems should be required. In this study, we developed intracellular metabolite sensor named “riboselector” to regulate metabolic distribution will be presented. The potentials of the platform technology developed in this study for the application to the production of biofuels and commodity chemicals.
Linda Kahl is a legal scholar at Stanford University, where she leads the Ownership, Sharing, Access, and Innovation Systems (OASIS) project for SynBERC, a multi-university NSF Synthetic Biology Engineering Research Center. Originally trained as a research scientist, Linda received her Ph.D. in biochemistry and cell biology from Princeton University, and worked as an independent consultant for numerous biotechnology companies, pharmaceutical companies, and research institutes in the areas of molecular diagnostics, infectious diseases, cancer research, biomarker discovery, genomics, and medical economics.
Linda’s interests led her to study intellectual property law and she received her J.D., magna cum laude, from Santa Clara University. She has been admitted to law practice in California and before the U.S. Patent and Trademark Office. Her current research focuses on how intellectual property rights might be adapted and applied to best support innovation in synthetic biology and biotechnology, more broadly.
Realizing constructive applications of synthetic biology requires the continued development of enabling technologies as well as policies and practices to ensure these technologies remain accessible for research and commercial development. Because the field of synthetic biology spans a wide range of disciplines – from engineering and biology to mathematics and computer science – the technologies considered “enabling” by synthetic biology researchers are expected to cover a broad range. We surveyed a community of self-identified practitioners engaged in synthetic biology research in order to obtain their opinions and experiences with technologies that support the engineering of biological systems. The results of our survey show the technologies enabling synthetic biology research are evolving, with shifts in the use of physical assembly methods and software tools, widespread use of public registries, and early adoption of functional composition and data exchange standards. Many technologies are widely accessible, at least for research use, either by virtue of being in the public domain or through legal tools such as non-exclusive licensing. However, broad access to technologies for commercial purposes presents more of a challenge. Because useful applications of synthetic biology may embody multiple patented inventions, it will be important to create structures for managing property rights that will promote access to the foundational technologies needed for commercial development of synthetic biology products and services. Moreover, because synthetic biology research and development is conducted across multiple institutions in many countries, it will be important to adopt policies and practices that promote cross-institutional and transnational exchange of ideas, data, and technology. By monitoring the enabling technologies of synthetic biology and addressing the property rights, licensing practices, and regulatory policies covering those technologies, our hope is that the field will be better able to reach its full potential to promote human health and preserve the environment.
Jay Keasling received his B.S. in Chemistry and Biology from the University of Nebraska in 1986; his Ph. D. in Chemical Engineering from the University of Michigan in 1991; and did post-doctoral work in Biochemistry at Stanford University from 1991-1992. Keasling joined the Department of Chemical Engineering at the University of California, Berkeley as an assistant professor in 1992, where he is currently the Hubbard Howe Distinguished Professor of Biochemical Engineering. Keasling is also a professor in the Department of Bioengineering at Berkeley, a Sr. Faculty Scientist and Associate Laboratory Director of the Lawrence Berkeley National Laboratory and Chief Executive Officer of the Joint BioEnergy Institute.
Dr. Keasling’s research focuses on engineering microorganisms for environmentally friendly synthesis of small molecules or degradation of environmental contaminants. Keasling’s laboratory has engineered bacteria and yeast to produce polymers, a precursor to the anti-malarial drug artemisinin, and advanced biofuels and soil microorganisms to accumulate uranium and to degrade nerve agents.
Professor Kitney is Professor of BioMedical Systems Engineering; Chairman of the Institute of Systems and Synthetic Biology; and Co-Director of the EPSRC National Centre for Synthetic Biology and Innovation. He has published over 300 papers in the fields of synthetic biology, mathematical modelling, biomedical information systems, and medical imaging. Kitney was Chair of The Royal Academy of Engineering Inquiry into Synthetic Biology – Synthetic Biology: scope, applications and implications, published in May 2009.
Kitney was a member of the British Government’s working group on the development of a Roadmap for synthetic biology for the UK and a member of The Royal Society’s Working Party on Synthetic Biology. He is a member of the British Government’s Leadership Council for Synthetic Biology and a member of the group developing a strategy for synthetic biology for the EU. With Professor Paul Freemont and other colleagues, he has been responsible for six highly successful Imperial College iGEM teams.
Project Managment Jülich, Division Biotechnology, EU und Internationales
Forschungszentrum Jülich GmbH
Radha Krishnakumar, PhD. Synthetic Biology and Bioenergy, J.Craig Venter Institute, 9704, Medical Center Drive, Rockville, MD 20850
In February of 2013, scientists and policy analysts from the J. Craig Venter Institute and SynBERC held a workshop on Intrinsic Biocontainment, focusing primarily on the state of science of biocontainment of synthetic and engineered organisms and its future possibilities. The objective of this workshop was to discuss biocontainment alternatives for engineered organisms used in both contained facilities and intended for release into the environment. In this session, a synopsis of the proceedings of this workshop will be presented, including a review of the history of biocontainment and methods currently in use, and advantages and limitations of the approaches in progress. The categories of methods that were discussed included self-destruct mechanisms and kill switches, engineered metabolic limitations including auxotrophy and complex circuits, and rewriting of the genetic code through the addition of non-standard amino acids and XNAs. I will also discuss some of the overarching questions raised during the workshop regarding the evolutionary and ecological traits of synthetic and engineered microorganisms, as well as some fundamental questions concerning the stability of synthetic and engineered circuits and genomes.
Stephen Laderman, Ph.D. is Director of the Molecular Tools Laboratory at Agilent Laboratories. He directs R&D programs aimed at inventing and developing leading-edge measurement solutions for research and diagnostics. His Lab applies biology, chemistry, and computer science expertise to the investigation and development of novel reagents, assay protocols, and computational methods that enable new methods in emerging fields within molecular cellular biology, molecular medicine and synthetic biology.
After receiving his A.B. from Wesleyan University in physics and his Ph.D. from Stanford University in Materials Science and Engineering, Laderman joined Hewlett-Packard Laboratories in 1984 as a member of technical staff, subsequently holding a variety of research and management positions there and in technology intensive businesses. In 1996, he headed a new project team made up of chemists and biologists devoted to the development and application of HP’s first DNA microarray products.
In 2005, Laderman received Agilent Laboratories’ highest award, the Barney Oliver Prize for Innovation.
Dr. Wolfgang Laux, Industrialization Coordinator for Major Products and New Chemical Entities with Sanofi Chimie since 2006. In this position, the mission is to evaluate, propose and coordinate the installation of industrial development plans allowing IA Chemistry & Biotechnologies group to meet requirements in active ingredients production. Head of the semi-synthetic Artemsinin project team since Feb 2012 with the objective to finish the industrialization and bring the new product to the market (validation and registration).
2000 to 2006: Project Manager in process development. PhD from Johann Wolfgang Goethe University in Frankfurt (Germany) on enantioselective synthesis of Hydroxyphosphonates. Postdoctoral Fellow in Montpellier (France) and Stony Brook (SUNY) with a Feodor-Lynen Research Stipend of the Alexander von Humboldt-Foundation.
The realization of the semisynthetic artemisinin project is a success story for global teamwork between industry, academia and nonprofit-organizations and shows examplary how an innovation on labscale becomes an industrial reality contributing to global health. Global demand for artemisinin, the key ingredient of artemisinin-based combination therapies (ACTs), has increased since the World Health Organization identified ACTs as the most effective malaria treatment available. Because the existing botanical supply of artemisinin – derived from the sweet wormwood plant – is inconsistent, having multiple sources of high-quality artemisinin will strengthen the artemisinin supply chain, contribute to a more stable price, and ultimately ensure greater availability of treatment to people suffering from malaria. The development of a new commercial-scale alternative manufacturing process to produce a complementary source of artemisinin started nine years ago, led by OneWorld Health, and funded by the Bill & Melinda Gates Foundation. The project built upon pioneering synthetic biology work done at the University of California, Berkeley (UC Berkeley), and involved a team of public and private partners, including Sanofi and the synthetic biology innovator, Amyris, Inc., to take the project from laboratory research to commercialization. This innovative industrial process to produce semisynthetic artemisinin consists in the production of artemisinic acid through fermentation – which is performed by Huvepharma, in Bulgaria – followed by a synthetic transformation of the artemisinic acid into artemisinin via photochemistry, which is performed by Sanofi in (Garessio, Italy). The realization of this project is a pivotal milestone in the fight against malaria, which affects about 300 million people every year and was responsible for more than 650,000 deaths in 2010.
Sang Yup Lee
Sang Yup Lee received B.S. in Chem. E. from Seoul National University, and Ph.D. in Chem. E. from Northwestern University. Currently, he is Distinguished Professor, Dean of KAIST Institutes, and Director of Center for Systems and Synthetic Biotechnology, BioProcess Engineering Research Center, and Bioinformatics Research Center at KAIST.
He has published more than 430 journal papers, and numerous patents. He received many awards, including the National Order of Merit, Citation Classic Award, Elmer Gaden Award, Merck Metabolic Engineering Award, ACS Marvin Johnson Award, SIMB Charles Thom Award, and Amgen Biochemical Engineering Award. He is currently Fellow of AAAS, American Academy of Microbiology, Society for Industrial Microbiology and Biotechnology, American Institute of Chemical Engineers, Korean Academy of Science and Technology, and National Academy of Engineering of Korea.
He is also Foreign Associate of National Academy of Engineering USA, Editor-in-Chief of Biotechnology Journal, and editor and board member of many journals.
Bio-based production of chemicals, fuels and materials by microbial fermentation of non-food renewable biomass has become increasingly important due to our increasing concerns on the limited fossil resources and environmental problems. In order to improve the performance of naturally isolated microorganisms, metabolic engineering needs to be performed. Rapid advances in systems biology and synthetic biology are enabling us to approach biological and biotechnological problems at systems level with abilities to finely design and control the metabolic and regulatory circuits. Thus, it is now becoming possible to perform metabolic engineering at the systems level. In this lecture, I will present the general strategies for systems metabolic engineering of microorganisms for the efficient production of chemicals, fuels and materials. The use of synthetic small regulatory RNAs to engineer metabolism at the systems-level will also be described. Several examples on redesigning cellular metabolism for the production of various chemicals and materials will be described. [This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries and by the Intelligent Synthetic Biology Center through the Global Frontier Program from the Ministry of Education, Science and Technology through the National Research Foundation of Korea.]
Suzanne Lee is the Founder and Director of BIOCOUTURE LTD, a pioneering and unique consultancy focused on bringing emergent biomaterials, biodesign and biofabrication to future consumer products. BIOCOUTURE clients span two worlds. By partnering with key material innovators and global brands we’re visioneering how a bio-designed future will look, feel and function. We believe synthetic biology offers solutions to today’s sustainability challenges as well as envisioning radical new product types and functionality.
The BIOCOUTURE clothing project has received worldwide media attention featuring in many design books and journals, most recently in William Myers 2012 book ‘Biodesign: nature, science, creativity’. Suzanne is author of the groundbreaking text ‘Fashioning The Future: tomorrow’s wardrobe’ published by Thames & Hudson. She speaks and consults internationally and is a TED Senior Fellow.
‘Haute Couture’ refers to the well-defined standards in custom dressmaking. Design and construction are hand-executed ensuring the unique specifications of each customer are met. Nineteenth century couturier, Charles Frederick Worth, was revolutionary for combining individual tailoring with standardisation enabling accurate duplication of designs around the world. Couture’s personalised, precise tuning of desired characteristics seems to share striking synergies with synthetic biology.
Materials engineered from scratch offer radical visions to our contemporary search for more sustainable solutions. The ultimate flexibility and creativity of design and construction allows for unprecedented, elegant efficiencies. What new opportunities and challenges do the ability to engineer novel organisms present? Can couture biology meet our nutritional, wellbeing, material, social, environmental and economic needs?
What does the world of synthetic biology mean for tomorrow’s designers when design, materials and manufacture are no longer discrete fields?
Tim Lu, M.D., Ph.D. is an Assistant Professor leading the Synthetic Biology Group in the Research Laboratory of Electronics and the Department of Electrical Engineering and Computer Science and the Department of Biological Engineering at MIT. He is a core member of the MIT Synthetic Biology Center and a co-founder of Sample6 Technologies, a Boston-based company that is delivering a revolutionary microbial diagnostic based on synthetic-biology-derived technologies.
Tim’s research at MIT focuses on engineering integrated memory and computational circuits in living cells using analog and digital principles, applying synthetic biology to tackle important medical and industrial problems, and building living biomaterials that heterogeneously integrate biotic and abiotic functionalities.
Natural biological systems incorporate both living and non-living components to achieve a diversity of functions. For example, bone is composed of osteoclasts and osteoblasts which can sense external signals and remodel the extracellular matrix to change mechanical characteristics. Bacterial biofilms synthesize proteins, nucleic acids, and polysaccharides to build hydrated extracellular matrices that protect them from outside insults.
Inspired by natural systems and leveraging the tools of synthetic biology, we present our efforts to engineer living biomaterials that incorporate living cells containing synthetic gene circuits with non-living extracellular materials. Central to this idea is the ability to endow the cellular aspects of living biomaterials with novel computational functions. Here, we describe scalable frameworks for constructing synthetic gene networks that implement digital and analog computation paradigms and integrated memory devices. Digital systems are useful for performing cellular decision-making and logic and can be constructed with concomitant DNA-encoded memory using libraries of orthogonal recombinases. Analog systems are useful for achieving wide-dynamic-range biosensing and complex mathematical functions. We shall present our efforts to create analog circuit motifs that perform wide-dynamic-range logarithmic transformations, addition, subtraction, multiplication, division, and power laws.
Ultimately, our goal with these platforms is to integrate synthetic gene circuits in living cells with abiotic materials to build heterogoenous living biomaterials with the ability to sense and respond to environmental conditions, self-assemble multiscale structures with tunable mechanical properties, repair themselves, and achieve new interfaces between living and non-living systems.
Claire is Senior Research Fellow in the Department of Social Science, Health & Medicine at King’s College London. She conducts social science research on biosciences and biotechnology, and for the last four years her work has focused on synthetic biology. Her current research takes place within the EPSRC-funded Centre for Synthetic Biology and Innovation (CSynBI), where she plays a key role in the implementation of responsible research and innovation.
She wrote a report for the Royal Society in 2011 about the transnational governance of synthetic biology, was in 2012 a member of the coordination group that produced the UK Synthetic Biology Roadmap, convened by the UK Department for Business, Innovation and Skills, and is a member of the expert group Observatoire de la Biologie de Synthèse convened by the French Ministry for Higher Education and Research.
Esteban Martinez Garcia
Esteban Martínez García obtained his Ph.D. at Universidad Complutense in Madrid in 2001, where he worked on stationary phase in bacteria. After that, he moved to the US for postdoctoral positions, first, in Roberto Kolter’s lab at the Harvard Medical School working on comparative genomics of Pseudomonas aeruginosa, and then at Kevin Foster’s lab at Harvard University working on the social interactions of P. aeruginosa.
In 2008, he returned to Spain, where he is currently in Victor de Lorenzo’s lab at Centro Nacional de Biotecnología in Madrid. His work is focused on developing standard genetic tools and in the modification of the adhesive properties of Pseudomonas putida, to re-programme its stickiness, with the final aim of engineering artificial communities.
The prokaryotic world is the largest reservoir of enzymatic activities in the Biosphere, but the vast majority of this treasure trove has not yet been exploited. To overcome this state of affairs new conceptual and material tools, as well as understanding of a large number of fundamental biological processes (e. g. metabolism) are required. Key aspects include optimization of a limited number of genomic and biochemical chasses compatible with environmental applications, standardization of methods of physical assembly of DNA constructs, development of genetic tools for deployment and stable maintenance of the implanted traits and adjustment of the engineered property to the genetic and biochemical background of the host. In this context, we have developed a large number of molecular tools for designing strains of the soil bacterium Pseudomonas putida aimed at biosensing and / or biodegradation of recalcitrant chemicals that are environmental pollutants. This multi-tiered effort involves [i] editing and streamlining of the existing genome for deletion of non-desirable segments (eg prophages) and enhancement of beneficial functions (eg stress tolerance), [ii] adoption of the so called Standard European Vector Architecture (SEVA) format for analysis, construction and deployment of genetic constructs in Gram-negative bacteria other than E. coli and [iii] development of fusion partners for targeting expression of given proteins to various cell compartments. The value of such standards (as well as their shortcomings) will be exemplified in our efforts to engineer P. putida strains for various applied purposes.
Vitor Martins dos Santos
Vítor Martins dos Santos holds the Chair for Systems and Synthetic Biology at the Wageningen University, The Netherlands, is the Director of the Wageningen Centre for Systems Biology and President of the Dutch Society of Biotechnology. He received a doctorate on environmental bioprocess engineering at Wageningen University. He did a post-doc in the Dept. of Molecular Biology of the Spanish Research Council (CSIC) in Granada, Spain and moved subsequently to the German National Centre for Biotechnology where he built the Systems and Synthetic Biology research group.
He has coordinated and participated in numerous national and international projects in Systems and Synthetic Biology and has been involved in advising science and governance policies, and has carried out intense research in the field. A major thrust of his research is the streamlining of microbial chassis and (computer-assisted) re-programming of cellular behaviour for medical, industrial and environmental applications.
We report on the construction of a genome-streamlined bacterium cell endowed with assembled genetic circuits for the production of high added-value aromatics and bioplastics. We developed and validated experimentally a genome-scale, model framework of the metabolism and transport of the biocatalytic chassis, Pseudomonas putida. Predictions pin-pointed interventions that, once implemented in-vivo through combinations of mutants and feeding strategies, enabled re-programming of carbon metabolism for a stark increase in the production of high-value precursors of bioplastics and fine-chemicals. To simplify and stabilize the chassis, we streamlined the 6-megabase genome through a newly developed excision method based on the combination of customized mini-transposons and the FLP-FRT site-specific recombination system. After 4 cycles, we shed 8% of the genome, thereby simplifying cellular wiring with no negative impact on the fitness. Genome-wide analyses of the streamlined chassis – through combined mathematical modelling and experiments – yielded new insights into the metabolism and regulation of this industrial bacterium. In parallel, we developed and experimentally validated a detailed dynamic model of the circuit coded by the pWW0 plasmid (a plug-and-play circuit for the biotransformation of aromatics). The model revealed that the architecture of the key regulatory node of the promoter system Ps/Pr can discriminate between alternative and competing carbon sources, which is of utmost relevance for biocatalyis of aromatic-derived fine chemicals. The study of the interplay between the biocatalytic circuit and the metabolic wiring of the chassis revealed unexpected mechanisms that control the expression of the “plugged-in” circuit. This workflow generated a streamlined bacterial factory, devoid of unnecessary gene complements and undesired cross-talk, thereby enabling a higher degree of control and, hence re-programming, by plugging-and-playing at will.
Dr. Mathews is the Assistant Director for Science Programs for the Johns Hopkins Berman Institute of Bioethics, an Assistant Professor in the Department of Pediatrics, and Affiliate Faculty in the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine. Dr. Mathews earned her BS in Biology from the Pennsylvania State University and PhD in genetics from Case Western Reserve University, where she earned a concurrent Master’s degree in bioethics. She completed post-doctoral fellowships in both genetics, and bioethics and health policy.
Within the Berman Institute, Dr. Mathews is responsible for overseeing the Stem Cell Policy and Ethics program and the Program in Ethics and Brain Sciences, as well as other Institute initiatives in policy and ethics related to biomedical research and emerging technologies, including genetics and synthetic biology. Dr. Mathews’s research interests focus on the intersection of science, ethics and public policy.
Just as the founders of a scientific field are responsible for laying the experimental groundwork for that field, so too do they have a responsibility for laying the ethics and governance groundwork. As synthetic biology grows and matures as a field, it can learn from other areas of biomedicine about how early decisions can shape downstream development and use. In this talk, I will draw on the experience of the regenerative medicine and genetics communities for lessons for today’s synthetic biologists.
Head of Strategy: Genomics, Data and Technologies
Biotechnology & Biological Sciences Research Council (BBSRC)
Holly Million is the Executive Director of the BioBricks Foundation. She has been a nonprofit management consultant for two decades, working for such organizations as Interplast, SFJAZZ, KTEH Public Television, Goodwill, Amnesty International, and others. Million is a staunch champion of democracy and the common good who has dedicated her life to the nonprofit sector.
As a consultant, teacher, writer, and filmmaker, Million has educated and empowered people to solve problems and make the world a better place. At the BioBricks Foundation, Million’s focus has been to help shape the organization as a force to promote biotechnology in the public interest.
Dr. Héctor Ricardo Morbidoni, Principal investigator, Dept. of Microbiology, School of Medical Sciences, National University of Rosario. Argentina Education: Pharmacy, Biochemistry, Industrial Microbiology (National University of Buenos Aires, Argentina), Ph.D. Biological Sciences (National University of Rosario, Argentina).
Areas of interest: Mycobacterial physiology and molecular biology, mechanisms of action of anti-tubercular drugs, mycobacterial mechanisms of resistance, Bacteriophage molecular biology and biotechnological applications, biosensors
Milan Mrksich is the Henry Wade Rogers Professor at Northwestern University, with appointments in Biomedical Engineering, Chemistry and Cell & Molecular Biology. He attended the University of Illinois, earning a BS degree in Chemistry, his PhD at Caltech and was an American Cancer Society Postdoctoral Fellow Harvard University before joining the faculty at the University of Chicago as an Assistant Professor in 1996.
Among his many honors are the Camille Dreyfus Teacher-Scholar Award (2000), the TR100 Young Innovator Award (2002), ACS Arthur C. Cope Young Scholar Award (2003), and election to the American Association for the Advancement of Science (2006). His research program lies at the intersection of chemistry, materials and biology and emphasizes the design and preparation of materials for applications in chemical biology and bioanalytical science. He has served on the Scientific Advisory Boards of several life sciences companies.
The reactions of molecules in the cell occur in highly non-uniform settings. Enzymes, cofactors, and substrates are rarely present at uniform concentrations throughout the cell but rather are spatially organized into regions of high and low concentration. These concentration profiles and the ways in which they are temporally regulated are essential to the normal operation of the reaction networks that underlie cell function. Yet, mechanistic studies of the unique factors that stem from spatio-temporal structuring of reactants are challenging. This seminar will describe a model system wherein enzymes act on immobilized substrates, with several unusual features. We show that a kinase which can associate with the phosphopeptide it generates will display an autocatalytic reaction profile. Further, the reaction generates spatial patterns of the product and shows an initial rate that varies with geometrical pattern, but not the ratio, of substrate and product. When reactions are performed in the presence of an opposing phosphatase, the direction of the phosphorylation reaction shows a dependence on the density of the substrate. This last observation points to a new motif for regulating phosphorylation events at the cell membrane and we engineer cells that display a kinase-dependent transmembrane signaling event in response to clustering of a chimeric receptor. This work provides an example of the unique features that derive from biochemical reactions in non-uniform environments.
Dr. Sarah Munro is a bioengineer in the Biosystems and Biomaterials Division of the Material Measurement Laboratory at the National Institute of Standards and Technology (NIST). She develops reference materials, data, and methods to provide confidence in biological measurements.
Her current research efforts include analysis of RNA external spike-in controls for method validation in RNA sequencing gene expression measurements, integration of functional genomics measurements to design new proteome reference materials, and development of new technical programs in metrology to support synthetic biology applications. She completed a National Research Council postdoctoral research associate award term at NIST and earned her Ph.D. in Biological and Environmental Engineering from Cornell University.
In the Biosystems and Biomaterials Division at NIST we develop measurement science infrastructure – standards, data, methods, and technology – to support characterization of complex biological systems and biomaterials. We’ve recently begun to consider measurement science needs in synthetic biology. A major focus of our research is development of standards for genome-scale measurements. Through the External RNA Controls Consortium we’ve developed a certified reference material for RNA spike-in control mixtures to use in gene expression measurements. These spike-in controls and the open-source analysis methods we’ve created provide the capability to assess technical performance of gene expression measurements. Through the Genome in a Bottle consortium we are currently developing whole genome reference materials and analysis methods. Synthetic biology is one focus of our new research partnership with Stanford University and private sector affiliates, the Advances in Biomedical Measurement Science (ABMS) program.
Richard M. Murray received the B.S. degree in Electrical Engineering from California Institute of Technology in 1985 and the M.S. and Ph.D. degrees in Electrical Engineering and Computer Sciences from the University of California, Berkeley, in 1988 and 1991, respectively. He is currently the Thomas E. and Doris Everhart Professor of Control & Dynamical Systems and Bioengineering at Caltech.
Murray’s research is in the application of feedback and control to networked systems, with applications in biology and autonomy. Current projects include analysis and design biomolecular feedback circuits; specification, design and synthesis of networked control systems; and novel architectures for control using slow computing.
We are developing a set of “biomolecular breadboards” to create a systematic, engineering-oriented approach to synthesizing biomolecular circuits that involves developing, modeling, and debugging a sequence of prototype devices, each at increasing levels of complexity and each allowing the incorporation of increasingly realistic operating environments for either in vitro or in vivo applications. Our goal is to reduce the iteration time for multiple prototype circuit designs to no more than a day and to design and implement novel, working circuits in cells in as little as a week. I will focus on our work on using cell-free extracts for this purpose and summarize some of our recent results in modeling, prototyping, debugging and implementing biocircuits using this breadboarding framework.
Birger Lindberg Møller
Birger Lindberg Møller obtained his PhD and DSc from the University of Copenhagen in 1975 and 1984. He is Professor at the Plant Biochemistry Laboratory at the University of Copenhagen. In the period 1998-2008 he served as Head of Center for Molecular Plant Physiology (PlaCe) founded by the Danish National Research Foundation. In 2008, he was appointed Director of the research centre “Pro-Active Plants” supported by the Villum Foundation and in 2010, Director of the Center for Synthetic Biology funded by the Danish Ministry of Science.
In 2011 he became Director of the section for “Plant Pathway Discovery” in the Novo Nordisk Foundation Center for BioSustainability. One of his main research interests within synthetic biology is the design of light driven production systems for the synthetis of bio-active natural plant products like structurally complex diterpenoids.
Photosynthetic organisms are able to use solar energy and carbon dioxide for the production of organic compounds. Based on initial formation and subsequent turn-over of carbohydrates, plants channel energy flux and carbon into specific biosynthetic pathways to optimize growth and development and adapts to abiotic and biotic environmental challenges by producing bioactive defense compounds. Several of these compounds are structurally complex and highly valuable pharmaceuticals used in the treatment of serious human diseases like cancer. Unfortunately such compounds are typically produced in small amounts by plants and sometimes also in plant species difficult to grow on a commercial scale. Most of the pathways responsible for the formation of the compounds involve cytochrome P450 catalyzed key steps difficult to copy using organic chemical synthesis. Using the “share-your- parts” principle of synthetic biology, we have now succeeded in breaking the evolutionary compartmentalization of energy generation and production of bioactive compounds. As proof-of-concept, we have relocated the entire P450 dependent pathway for the cyanogenic glucoside dhurrin to the chloroplast. The P450s were incorporated into the thylakoid membranes and shown to be driven by the reducing power generated by photosystem I with reduced ferredoxin as the direct electron donor to the P450s. Likewise, it was possible to directly incorporate P450s into the photosystem I reaction center complex by using some of the small subunits of this complex as membrane anchors instead of the native P450 anchors with the long term goal of building a supra-molecular enzyme complex catalysing light driven synthesis of pharmaceuticals and other interesting bioactive molecules. The production systems are being developed and optimised using transient expression in tobacco as the experimental system followed by stable transformation of cyanobacteria and moss strains grown in closed photobioreactors. Key target compounds are structurally complex diterpenoids.
- TED talk: http://www.youtube.com/watch?v=6oiWJOTydWA
- Redirecting Photosynthetic Reducing Power toward Bioactive Natural Product Synthesis A.Z. Nielsen, B. Ziersen, K. Jensen, L.M. Lassen, C.E. Olsen, B.L. Møller, and P.E. Jensen: ACS Synth. Biol., February 19, 2013 DOI: 10.1021/sb300128r
After receiving his Ph.D. in Hamburg (1986) and serving on the faculty of the Philosophy Department at the University of South Carolina (1988-2002), Alfred Nordmann became Professor of Philosophy and History of Science at Darmstadt Technical University.
His current focus is on the development of a comprehensive philosophy of technoscience that reflects recent changes in the culture of science and the changing relationship of science, technology, nature and society. Since 2000 Nordmann has been studying philosophical and societal dimensions of nanoscience and converging technologies, climate engineering and synthetic biology.
In order to address the question of “Responsible Innovation” we have to ask in which ways Synthetic Biology is innovative in the first place: Are we looking at ways to responsibly redesign the biosphere, to responsibly bioengineer particular organismic structures? Or is SynBio innovative in how it shapes a new generation of researchers or in its adoption of new design processes or methods for knowledge production? The notion of “responsible representation” foregrounds intellectual honesty regarding the values and commitments that inform the adoption of research methods and research goals. If SynBio is defined mostly by its “innovative mind-set”, what is the cultural meaning of this mind-set and what are the associated questions of responsibility towards science, history, society, and the next generation of researchers? Among the examples to be discussed: What is the meaning of and how can one take responsibility for the Feynman-maxim “What I cannot create, I do not understand”?
Carlos Olguin heads the Bio/Nano/Programmable Matter Group at Autodesk Research. Formed three years ago, Carlos leads the 18-member group investigating the design spaces enabled by matter programming across domains and scales by collaborating with researchers around the world to co-envision the paradigms and tools needed to establish a robust scale-free body of knowledge of design.
Carlos is an interdisciplinary designer with more than 13 years of combined experience in domains such as design tools for 2D and 3D modeling, learning, GIS, risk management, network service brokerage, web search experience, online emergent social phenomena, and systems/synthetic biology. Carlos holds an MS in Information Networking from Carnegie Mellon and a B.Sc. in Electronics and Communications from ITESM Campus Monterrey (Mexico).
Carlos has also studied telecommunications at the Institute National des Telecommunications in Evry, France, and taken accredited courses in Systems Biology at the University of Gothenburg and Columbia University.
Professor Anne Osbourn leads the Institute Strategic Programme on Understanding and Exploiting Plant and Microbial Metabolism at John Innes and is also an Associate Research Director of the Centre. Her research focuses on plant-derived natural products – function, synthesis and metabolic diversification. Anne’s group works with crop and model plants, and uses a wide range of multidisciplinary approaches including genetics, genomics, computational biology, cell biology, protein and small molecule biochemistry.
An important advance from the Osbourn laboratory has been the discovery that genes for specialized metabolic pathways are organized in ‘operon-like’ clusters in plant genomes, a finding that has opened up new opportunities for elucidation of new pathways and chemistries through genome mining.
Anne is a member of an international synthetic biology consortium jointly funded by the Engineering and Physical Sciences Research Council (UK) and the National Science Foundation (US) that aims to develop methods for directed evolution of metabolic pathways using recombinase-based multi-gene assembly platforms. She has also developed and co-ordinates the Science, Art and Writing (SAW) initiative, a cross-curricular science education programme for schools (www.sawtrust.org).
Plants produce a tremendous array of natural products (many of which are specialised metabolites associated with particular species), including medicines, flavours, fragrances, pigments and insecticides. The vast majority of this metabolic diversity is as yet untapped, despite its huge potential value for humankind. So far, research into natural products for the development of drugs, antibiotics and other useful chemicals has tended to focus on microbes, where genome sequencing has revolutionised natural product discovery through mining for gene clusters for new metabolic pathways. Identifying novel natural product pathways in plants is extremely difficult because plant genomes are much larger and more complex than those of microbes. However, the recent discovery that genes for some types of plant natural product pathways are organised as physical clusters is now enabling systematic mining of plant genomes in the quest for new pathways and chemistries. Improved understanding of the genomic organization and regulation of different types of specialized metabolic pathways will shed light on the mechanisms underpinning pathway and genome evolution. It will also open up unprecedented opportunities for exploiting Nature’s chemical toolkit.
Qi Ouyang, Chang-Jiang special Professor at Peking University, China. Director of the Institute of Condense Matter Physics, School of Physics; associate director of the Center for Quantitative Biology, School of Advanced Interdisciplinary Studies, Peking University. Professor Qi Ouyang is specialized on the nonlinear dynamics and pattern formation research in reaction-diffusion system.
From 1996, he started to study biophysics related researches by applying the concept and method of nonlinear dynamics and stochastic physics in living system. His current interests in biology field include biological regulation network dynamics, bio-microfluidics, and synthetic biology.
The main purpose of synthetic biology is to develop basic biological functional modules, and through rational design, develop man-made biological systems that have predicted useful functions. In this talk, I will discuss two methods in rational design of functional biological circuits: the forward engineering and the reverse engineering. Both methods are proven to be successful in electronic engineering. I will use two synthetic biology researches that conducted in my laboratory at Peking University to illustrate the above principles. The first example is to use forward engineering design to synthesis “Pavlov bacteria” which can perform learning and recalling functions; The second example is to use reverse engineering design to synthesize a cell which has a semi-log dose-response to the environment. These works demonstrate that design principles in electronic engineering can be transplant into synthetic biology, but one should pay special attention to the difference between electronic engineering and biological engineering.
Professor Richard Owen holds the Chair in Responsible Innovation at the University of Exeter Business School. He researches how innovation and science might be governed towards societally desirable and acceptable ends, associated challenges and opportunities and how responsibilities are perceived and distributed.
His research is strongly interdisciplinary, with a continuous emphasis on practice – he has worked closely with the UK Research Councils to develop a framework for responsible innovation and is investigating its application in diverse areas, from geoengineering and nanotechnologies to finance and synthetic biology.
His research group is studying the historical framing of responsibility, the governance of financial innovation, horizon scanning, innovation of sustainable business models and eco-innovation at the ‘Bottom of the Pyramid’ – how some of the World’s poorest people are innovating to rise to the challenges of resource scarcity and sustainability. Richard is a strategic advisor to EPSRC and co-ordinates the RCUK Environmental Nanoscience Initiative.
Public dialogues in synthetic biology and other areas of emerging science and technology have emphasised the need for researchers and those who fund them to think through and broadly deliberate on the ethical and wider implications of their research, in a way that influences how their area of science and technology develops. This has catalysed funding by the UK Research Councils that has led to the development a framework for responsible innovation which I will describe, as well as some experiments concerning how it might be implemented. I will argue the primary departure point for this framework is not ‘what are the risks?’ – important though this is – but ‘what sort of future do we want synthetic biology to bring into the world?’ and ‘how should we collectively proceed under conditions of ignorance and uncertainty?’ Anchored in concepts of responsibility that emphasise care and responsiveness the framework will build on integrated dimensions of anticipation, deliberation and reflection as these relate to both the products and purposes of innovation that are hardly new: it is their coupling to responsiveness at personal, institutional and political levels that is important and is prompting new conversations on role and responsibility.
- Responsible Innovation Framework Book Chapter (Open Access) http://media.wiley.com/product_data/excerpt/61/11199663/1119966361-3.pdf
Paulo Paes de Andrade
Paulo Paes de Andrade, 59, is Associate Professor at the Department of Genetics, Federal University of Pernambuco, which he joined in 1983. He is a Physicist, with MSc and PhD in Cell Biology and postdoctoral studies in molecular biology and immunology.
His research group collaborated in broad programs to study the transcriptome of Leishmania, and gene expression in plants, especially sugar cane, soya and beans. Various recombinant Leishamania antigens were isolated for molecular diagnosis of visceral leishmaniasis and one of them led to a patent, which was transferred to the private sector and is now employed in the sole recombinant diagnostic test produced in Brazil.
In 2006 Prof. Andrade joined the National Technical Commission on Biosafety (CTNBio), as a member of the Environmental Risk Assessment Sub-committee, with outstanding performance in analyzing submissions for confined and commercial relases of GMOs and in the drafting and revision of CTNBio rules and regulations.
GMO environment risk assessment recently evolved to maturity. The five main steps were established and, within the first step (Context), the five crucial elements have also been defined. The step by step procedure successfully applies to every genetically modified organism. There are presently no reports on environmental damage due to GMOs, in spite of the diversity of constructions and widespread use, thus confirming the robustness of the systematic. Environment risks due to organisms having synthetic constructs replacing genes or gene fragments can certainly be evaluated in the same way,in spite of the lack of a suitable comparator for a fully new construct. Naturally, the evaluation of a fully new organism will be the greatest challenge, but is still far from the market. Therefore, it is important for the industry and for consumers to clearly establish to the society the power and appropriateness of the present risk assessment systematic when applied for the first generation of organisms based on synthetic biology, in order to allow their commercial release. In fact, the same groups against biotechnology are also against synthetic biology and they are trying to separate the risk assessment of products derived from the two technologies in order to build an almost unsurpassable barrier for the new technology. Moreover, international agreements and conventions, like the Cartagena Protocol to the Convention of Biodiversity, are by themselves, also powerful limitations to the adoption of new product based on synthetic biology. To avoid general frustration among young scientists devoted to synthetic biology, the transition from discovery to innovation should be discussed now, before the opposition blocks every future attempt by overprecautionary regulations. The talk will detailed discuss this subject.
- cibpt.files.wordpress.com/2012/11/guia-avaliac3a7c3a3o-risco-ambiental-ogm-2012.pdf (Guide on risk assessment)
- The author states that this talk is the collaborative work of Maria Mercedes Roca, Marcia Almeida de Melo and himself.
Sven Panke received his degree in Biotechnology from the Technical University of Braunschweig in 1995 after work at the German National Research Centre for Biotechnology and the Centro de Investigaciones Biologicas (Madrid, Spain). He received his PhD in 1999 from ETH Zurich, Switzerland, after a stay with Bernard Witholt for his work on the production of fine chemicals with recombinant bacteria.
After a two year-stay in the biocatalysis group of the pharmaproduct group of the Dutch chemical company DSM (Geleen, The Netherlands), he returned to ETH in 2001 as an Assistant Professor for Bioprocess Engineering. After receiving tenure in 2007, he moved to the newly founded ETH Department of Biosystems Science and Engineering in Basel. His main research topics include integrated reaction-separation systems, high-throughput screening, and synthetic biology.
Juan Pablo Pardo-Guerra
Juan Pablo Pardo-Guerra is a Lecturer in Sociology at the London School of Economics. He studied physics at UNAM, Mexico, and holds an MSc and PhD in science and technology studies from the University of Edinburgh. He currently works on how technology transformed financial markets between 1970 and 2010.
His research stresses the role of engineers and designers in the making of financial markets. It also looks into the role of algorithms and economic models in contemporary financial markets. Along with that of colleagues from Edinburgh and LSE, his work has informed the UK government’s policy on the future of computer-based trading in financial markets.
Modelling is a widely used practice within the study of markets and the economy. Recent studies suggest, however, that economic modelling is not merely a tool for representing an objective and external reality but rather operates as an instrument for intervening in the world. Economic models do not illustrate abstracted features of the economy: they fundamentally constitute its core. In this presentation, I will explore the uses of models in finance and economics, from how they define the course of nations, to how they constitute the fabric of financial markets. In doing so, I will explore a century of modelling practices, from the invention of national accounts in the early twentieth century to the dominance of algorithms and computer models in contemporary financial markets.
Andrew Phillips is head of the Biological Computation Group at Microsoft Research Cambridge, where he is conducting research into programming languages and methods for simulating and analysing biological systems. Andrew received a postgraduate degree in Computer Science from the University of Cambridge, under a scholarship from the Barbados government. He pursued a PhD in the Department of Computing at Imperial College London, where he worked on theory and implementation of concurrent, distributed programming languages.
He joined Microsoft Research Cambridge in 2005, to conduct research at the intersection of programming language theory and biological modelling. In 2011 he received a Technology Review TR35 award for work on software for computer-assisted genetic engineering. The award recognises technology innovators under the age of 35. His hobbies include snowboarding and kite-surfing.
Cells are the building blocks of life. If we could program living cells as effectively as we program digital computers we could make breakthroughs in medical treatment, sustainable agriculture and clean energy, while also better understanding how living systems compute. In spite of this potential there are still many challenges to overcome. Programming cells is highly complex and error-prone, and we are at a point where powerful computer software could significantly accelerate further progress. This talk presents ongoing work to develop computer languages for programming cells at three levels: molecular circuits, genetic devices and cell colonies. We present a language for programming molecular circuits made of DNA, and for characterising genetic parts that can be combined into devices for programming cell function. Finally, we present software for simulating cell biofilms using 3D biophysical methods, which can be used to predict the effect of cell shape on colony morphology. Just as languages for programming digital computers heralded a new era of technology, languages for programming cells could enable new industries in biotechnology.
Fiona Raby is a partner in the design partnership Dunne & Raby, established in 1994.
She is professor of Industrial Design at the University of Applied Arts in Vienna, and a Reader in Design Interactions at the Royal College of Art in London.
Dunne & Raby use design as a medium to stimulate discussion and debate amongst designers, industry and the public about the social, cultural and ethical implications of existing and emerging technologies.
Their work has been exhibited at MOMA, the Pompidou Centre, and the Science Museum in London and is in the permanent collections of MOMA, V&A, FRAC and FNAC. They have published two books: Design Noir: The Secret Life of Electronic Objects (Princeton Architectural Press) and Hertzian Tales (MIT Press). Speculative Everything: Design, Fiction and Social Dreaming will be published by MITPress November 2013.
Kent is Principal at Archipelago Consulting in Portland, Maine, USA. He has spent 30 years in the conservation world with a decade at the University of Florida, 5 years at The Nature Conservancy and 14 years at the Wildlife Conservation Society. He organized an April, 2013 meeting that brought together the synthetic biology and conservation communities to discuss linked futures.
The field of synthetic biology has just recently encountered the edges of the field of conservation biology (Conbio) and practitioners in both fields have yet to realize that there is much they should talk about. Conservation biologists are devoted to maintaining the variety and variability of life, often for its own sake. Synthetic biologists are interested in reducing variability to enhance performance for the sake of human ends. Conservationists are concerned about the increasing biotic homogenization of the world while synthetic biologists are interested in making hybrid organisms. So what responsibility does synthetic biology have towards the natural world from which it draws parts and inspiration, which will be affected by its creations, and in which its practitioners live? Are there wicked problems facing conservation that might be solved with the help of synbio? And what responsibility does conservation have towards organisms that are created by synthetic biologists? The time is ripe for an honest, broad conversation about human kind’s collective responsibility towards the natural world and the role that synthetic biology will play in its future.
Sarah M. Richardson received a B.S. degree in Biology from the University of Maryland in 2004 and a Ph.D. in Human Genetics from the Johns Hopkins University School of Medicine in 2011. Her research at Johns Hopkins with Joel Bader and Jef Boeke focused on algorithms for the design of synthetic nucleotide sequences.
Sarah joined the Lawrence Berkeley National Laboratory and the Department of Energy Joint Genome Institute in Walnut Creek, California in April 2012 as a Distinguished Postdoctoral Fellow in Genomics to work on massive scale synthetic biology projects in biogeochemistry and bioremediation.
The successful assembly of multikilobase pieces of DNA requires very careful top down design and planning. GeneDesign can manipulate restriction enzyme recognition sites, change codon usage, and smooth out repetitive regions to ease the design process. It can also direct simple, automatable assembly of synthetic constructs with a simple protocol that minimizes PCR and stages the parallel, stepwise assembly of up to 15kb pieces. This protocol has no special requirements for sequence, making it ideal for the assembly of large constructs on the plasmid scale.
For constructs on the chromosome scale, there is BioStudio. BioStudio is a framework for the multi-scale design of synthetic genomes. It can modify nucleotide sequences automatically or manually at multiple resolutions, using the GeneDesign libraries where appropriate. It can use the excellent, open-source, and user-friendly GBrowse as a GUI. It is currently able to select recognition sites for the physical assembly of designed sequence, identify and incorporate unique sequences for PCR identification of wildtype and synthetic sequence, edit existing genome features, and create and annotate user-created genome features. BioStudio annotates all changes to the genome sequence for version control, allowing the “roll-back” of any modifications with lethal phenotypes. When coupled with a modular design strategy, versioning allows genome synthesis to proceed with as little re-synthesis as possible.
Maria Mercedes Roca
Dr. Maria Mercedes Roca is Associate Professor of Biotechnology at Zamorano University, Honduras. She joined Zamorano in 1997, where she devotes part of her time to education projects, course design and curriculum development. She holds a doctoral degree in plant pathology and virology from the University of London, and a B.S. in microbiology from Kings College, London.
Dr. Mercedes Roca has lived and worked in the UK, Mauritius, Mexico, Bolivia, Colombia and Honduras. She joined the Norman Borlaug Institute of tropical agriculture at Texas A&M University in 2009 as faculty exchange member. She is the country representative for RedBio (Latinamerican Network for Biotechnology), was councillor of the Caribbean Division of the American Phytopathological Society, and organized an International Conference on Agriculture and Environment in 2012 attended by Ministers of Environment and Agriculture from Central America.
She is an advisor to the Honduran government on agricultural biotechnology regulation, and was a member of the Honduran delegation to the Rio+20 UN Conference on Sustainable Development in 2012. Dr. Mercedes Roca was invited in 2013 to join a group of international experts on risk analysis of genetically modified organisms by the Secretariat of the Cartagena Protocol on Biosafety of Biotechnology. She has a keen interest in the regulation and biosafety of synthetic biology and its potential for education in biological sciences.
This is not an orthodox paper about research results presented at an orthodox scientific meeting. It is an invitation to apply the tools of synthetic biology (SB) to solve some century-old problems of plant diseases in tropical crops that have proved intractable to solution by conventional tools such as plant breeding or pesticides. Coconut Lethal Yellowing killing 90% of palms of susceptible varieties on Caribbean beaches; frosty pod of cacao (chocolate) and coffee rust, which are drastically affecting production and income in Central America; Black Sigatoka disease of bananas where 30% of the costs of producing bananas is now due to pesticides used to fight the disease. Formidable challenges are also incredible opportunities for change. Humanity is embarking on a new powerful genomic revolution and the field of SB offers the promise to revolutionize biological sciences and contribute to agriculture. Scientists can bring solutions. Policy makers must acknowledge both the SB’s potential and the public’s deep mistrust for new, untested technologies they feel are outside their control. The future success of SB depends to a large extent on whether public policy is well-crafted. Both groups must work together to realize the potential.
Susan Rosser is a Professor in the Institute of Molecular, Cell and Systems Biology at the University of Glasgow and an EPSRC Leadership Fellow focused on Synthetic Biology. Susan studied microbiology and genetics at the university of Dundee before a PhD working on the mechanisms of multiple antibiotic resistance. Susan then moved to the Institute of Biotechnology at the University of Cambridge to work on biotransformations of cocaine and high explosives. She then became a lecturer in biotechnology at the University of Glasgow before being promoted to Professor in 2012.
She is the programme coordinator and PI of a large transatlantic synthetic biology project co-funded by the EPSRC and NSF which aims to develop synthetic biology tools for rapid generation, evolution and optimisation of genetic circuits and metabolic pathways. Her synthetic biology research interests focus on developing tools for rapid pathway assembly and modification, microbial fuel cells, logic gates and biocomputing, and tools for rapid industrial strain improvement.
One major target in Synthetic Biology is the creation of genetically modified organisms, to produce valuable chemical substances economically, in high yield and with low environmental impact, or to carry out beneficial chemical transformations. To create these organisms, it is often necessary to introduce a set of new genes and assemble them in specified positions within the organism’s genome. The genetic techniques currently available for this ‘assembly’ task are still inadequate, and gene assembly is considered to be a serious bottleneck in the work leading to the development of useful microorganisms. The first main aim of our research programme is to establish a sophisticated new methodology for this gene assembly process which will achieve a step- change in the speed and efficiency of creating new microorganism strains. For this purpose we have adapted a remarkable group of bacterial recombinases whose natural task is to carry out this kind of genetic rearrangement but which have hitherto been underused as tools for Synthetic Biology. We have designed rapid, robust and efficient ways of making gene cassettes that can be recombined in to specified positions in DNA. By doing this we can assemble collections of genes to order within a particular microorganism. Furthermore we can choose where to place the genes and in what order, and replace any individual parts with different versions. This permits much easier optimization of complex genetic systems than is currently possible. Using our new methods we intend to engineer microbial cells to make useful products e.g. next-generation biofuels, fine and platform chemicals.
Hans Roubos is Principal Scientist Bioinformatics & Modeling at DSM. He manages the Bioinformatics & Modeling group @ the DSM Biotechnology Center (Delft, The Netherlands). His team takes part in multidisciplinary project teams for Food, Feed, Pharma and Industrial Biotech and supports them with: DNA construct design, Protein engineering, Metabolic pathway engineering, Omics data mining, Sequencing and Biostatistics.
In addition, he manages a project team dealing with technology development for rational strain engineering including concepts related to standardization, parallelization and automation.
DNA sequencing and DNA synthesis have become key enablers for innovation in industrial biotechnology. Rapid developments in throughput and cost reduction have resulted in a completely new perspective on the design and generation of improved strains and enzymes with new functionalities.
DSM is a global player with application areas ranging from food, feed and pharma to bio-based chemicals and bio-based fuels. Thanks to bioinformatics, systems biology and the emergence of synthetic biology, we can now employ a rational approach towards metabolic and protein engineering. Standardization, parallelization and automation are key! Examples will be shown. Additionally, we will discuss how DSM would like to see standards coming from the synthetic biology community including education.
Dr. Iris Salecker is a program leader at the MRC National Institute for Medical Research in London (UK). She received a PhD degree in Neurobiology in 1995, investigating olfactory system development in hemimetabolous insects in the laboratory of Dr. Juergen Boeckh at the University of Regensburg (Germany). For her postdoctoral studies, she joined the group of Dr. S. Lawrence Zipursky at UCLA (USA), where she began to study photoreceptor axon guidance in the visual system of Drosophila.
In 2000, she moved to London to establish her first independent research group as a career-track and subsequently tenured program leader in the Division of Molecular Neurobiology at NIMR. She became part of the EMBO Young Investigator program in 2003, and an EMBO member in 2013. Combining genetic, molecular biology and imaging approaches, her team investigates the mechanisms underlying visual circuit assembly in Drosophila, with a special interest in axon-target and neuron-glia interactions.
Individual neuron subtypes have elaborate axonal and dendritic processes with characteristic shapes, reflective of their specific functions in neural circuits. Techniques that label single neurons within their complex environment are thus highly valuable additions to the neurobiologist’s toolbox. In 2007, Livet et al. developed the mouse Brainbow system, which enables the visualization of cells in multiple colors by the stochastic and combinatorial expression of three spectral variants of fluorescent proteins (FP). The Flybow system, which is based on the Brainbow-2 strategy, adapts this approach for use in Drosophila. It contains distinct features that take advantage of genetic techniques available in this model organism. Flybow transgenes are modular and combine modified DNA sequences from different organisms. These make it possible to induce recombination events and to drive expression of one of four membrane-anchored optimized FPs in any genetically accessible cell population of interest. Moreover, these features render the Flybow approach compatible with loss- and gain-of-function approaches. Using the fly visual system as an example, I will show how Flybow can support anatomical and functional studies of neuronal connectivity. Finally, I will discuss our current efforts in improving and expanding the functionality of our initial transgenes.
Dr. Herbert Sauro is an Associate Professor in the Department of Bioengineering at the University of Washington, Seattle. He has a BSc in Biochemistry/Microbiology and an MSc in Computing and Mathematics. He earned his Ph.D. in Computational Biochemistry from Oxford Brooks University, UK while working with David Fell where he helped develop metabolic control analysis and new simulation software. His postdoctoral work was at the University of Edinburgh with Henrik Kacser.
His interests include network architecture, control systems, software and standards development and synthetic biology. Within synthetic biology his group works on noise propagation through cellular networks, novel strategies for metabolic engineering, aptamer design and leads the development of the Synthetic Biology Open Language. He is also interested in online teaching methods and publishing affordable text books.
The Synthetic Biology Open Language (SBOL) is a community developed data standard for exchanging biological designs within the synthetic biology community. SBOL can be used to exchange designs between software tools, research groups, and commercial service providers. The re-use of previously published designs is important to develop synthetic biology from a research endeavor to an engineering discipline. As a community-driven standard, SBOL is designed to adapt as synthetic biology evolves, providing specific capabilities for different aspects of the synthetic biology workflow. This talk will give an update to recent developments in SBOL and the importance of community in this inception and evolution.
Associate Professor in the Department of Computer Science and Applied Mathematics at the Weizmann Institute of Science, Prof. Segal leads a multi-disciplinary team of computational biologists and experimental scientists working in the area of Computational and Systems biology.
Prof. Segal received several awards for his work, including the 2007 EMBO young investigator award, and the 2007 Overton prize by the International Society for Bioinformatics (ISCB), an award that is given to one scientist a year, in the early to mid career stage, for outstanding accomplishments in the field of computational biology. He published more than 80 research articles in peer-reviewed journals, of which more than 20 appeared in Science, Cell, or Nature (and its sub-journals). Prof. Segal was recently selected as a member of the young Israeli academy of science.
Genetic variation in non-coding regulatory regions accounts for a significant fraction of changes in gene expression among individuals from the same species. However, without a ‘regulatory code’ that informs us how DNA sequences determine expression levels, we cannot predict which sequence changes will affect expression, by how much, and by what mechanism. To address this challenge, we developed a high-throughput method for constructing libraries of thousands of fully designed regulatory sequences and measuring their expression levels in parallel, within a single experiment, and with an accuracy similar to that obtained when each sequence is constructed and measured individually. Using this ~1000-fold increase in the scale with which we can study the effect of sequence on expression, we designed and measured the expression of libraries in which the location, number, affinity and organization of different types of regulatory elements has been systematically perturbed. Our results provide several new insights into principles of gene regulation, bringing us closer towards a mechanistic and quantitative understanding of which how expression levels are encoded in DNA sequence.
Elaine Shapland is a Scientist at Amyris, where microbes are engineered to produce sustainable alternatives to a variety of consumer products. Her work across several projects has focused on advancing the industrial synthetic biology platform and speeding up the design-build-test cycle. She has successfully translated bench scale proof of concept experiments to integrated high throughput workflows.
She is also interested in how to best mentor, coach and educate scientific researchers at all levels so that they can work to their greatest potential. Previously she was at the University of California, Berkeley, where she received her Ph.D. in microbiology with Dr. Kathleen Ryan. Her doctoral research described the first essential tyrosine phosphatase in a bacterium and its effects on membrane structure during cell division.
Dr. Reshma Shetty graduated from MIT with a PhD in Biological Engineering in 2008 during which she worked on building digital logic in cells. Reshma has been active in synthetic biology for several years and co-organized SB1.0, the first international conference in synthetic biology in 2004. Her coolest genetically engineered machine to date was engineering E. coli to smell like mint and bananas.
In 2008, Forbes magazine named Reshma one of Eight People Inventing the Future and in 2011, Fast Company named her one of 100 Most Creative People in Business. Reshma and colleagues have founded synthetic biology company Ginkgo BioWorks, Inc. which makes and sells engineered microorganisms for food, fuels and pharmaceuticals production.
Christina D. Smolke is an Associate Professor, Associate Chair of Education, and W.M. Keck Foundation Faculty Scholar at Stanford University in the Department of Bioengineering. Professor Smolke’s research focuses on developing modular genetic platforms for programming information processing and control functions in living systems.
She has pioneered the design and application of RNA molecules that process and transmit user-specified input signals to targeted protein outputs, thereby linking molecular computation to gene expression. These technologies are leading to transformative advances in how we interact with and program biology and are being applied to address key challenges in scalable natural product biosynthesis platforms, cellular therapeutics, and targeted molecular therapies. She has been honored with the NIH Director’s Pioneer Award, NSF CAREER Award, Beckman Young Investigator Award, Sloan Research Fellowship, WTN Award in Biotechnology, TR35 Award, and Neekeyfar Lecturer.
Dr Stan received his PhD degree in Applied Sciences (Analysis and Control of Nonlinear Dynamical Systems) in March 2005, from the University of Liège, Belgium. In 2005, he worked as Senior Digital Signal Processing Engineer and R&D coordinator at Philips Applied Technologies, Leuven, Belgium. In 2006, he joined the Control Group of the Department of Engineering at the University of Cambridge, UK, being supported by a EU-FP6 IEF Marie-Curie Fellowship and the UK EPSRC. During summer 2008, he was an invited Visiting Scientist at the Laboratory for Information and Decision Systems, MIT, USA.
Since 2009 he is the head of the “Control Engineering Synthetic Biology” group at the Department of Bioengineering and the EPSRC-funded Centre for Synthetic Biology and Innovation. His research interests include the mathematical modelling, analysis and control of biological or technological systems using methods inspired from systems and control theory.
In this talk I will give a brief overview of some of the research activities in my group, the “Control Engineering Synthetic Biology” group, where we focus our efforts on developing foundational forward-engineering tools to mathematically model, and rigorously analyse, design and control synthetic gene circuits and cellular metabolism so as to endow engineered cells with novel functionalities. The tools and approaches that we take rely on principles drawn from Robust Optimal Control and Dynamical Systems theory, applied to Synthetic Biology problems.
Some of the topics covered will include (if time allows): (a) Design of in vivo genetic feedback controllers for automatic robust regulation of branched and unbranched metabolic pathways, and (b) Exogenous data-based optimal feedback control of gene regulatory networks.
(a) Among Synthetic Biology’s most prominent applications is the manipulation of bacterial metabolism for producing high-value chemicals in diverse sectors such as energy, biomedicine and food technology. In this regard, we are developing foundational tools for the analysis and design of feedback control synthetic biodevices that automatically regulate bacterial metabolism according to pre-defined objectives. Because these feedback controllers are intracellular, they have a great potential for applications where cellular behaviour needs to be controlled without real-time human intervention.
(b) In the second part of the talk, I will present research results pertaining to the inference of (close-to) optimal feedback control strategies for exogenous control of biological systems (natural or synthetic) directly from input-output measurements, i.e., without the need for identifying a mathematical model of the system’s dynamics a priori. The examples discussed include data-based inference of optimal control strategies for regulation and reference trajectory tracking in synthetic gene regulatory networks such as the toggle-switch or the generalised repressilator.
Molly Stevens is Professor of Biomedical Materials and Regenerative Medicine and the Research Director for Biomedical Material Sciences in the Institute of Biomedical Engineering at Imperial College London. She joined Imperial in 2004 after a Postdoctoral training in the field of tissue engineering with Professor Robert Langer in the Chemical Engineering Department at the Massachusetts Institute of Technology.
Prior to this she was awarded a PhD in biophysical investigations of specific biomolecular interactions and single biomolecule mechanics from the Laboratory of Biophysics and Surface Analysis at the University of Nottingham (2000). In 2010 she was recognised by The Times as one of the top ten scientists under the age of 40. Her most recent awards include the EU-40 Prize from the European Materials Research Society, the prestigious Griffith Medal and Prize from the Institute of Materials Minerals and Mining and the Clifford Paterson Lecture Award from The Royal Society.
Bio-responsive nanomaterials are of growing importance with potential applications including drug delivery, diagnostics and tissue engineering (1). A disagreeable side effect of longer life-spans is the failure of one part of the body – the knees, for example – before the body as a whole is ready to surrender. The search for replacement body parts has fuelled the highly interdisciplinary field of tissue engineering and regenerative medicine. This talk will describe our research on the design of new materials to direct stem cell differentiation for regenerative medicine (2). This talk will also provide an overview of our recent developments in the design of materials for ultrasensitive biosensing. Our recent simple conceptually novel approaches to real-time monitoring of protease, lipase and kinase enzyme action using modular peptide functionalized gold nanoparticles and quantum dots will be presented (3). Furthermore we have recently developed a new approach to ultrasensitive biosensing through plasmonic nanosensors with inverse sensitivity by means of enzyme-guided crystal growth (4) as well as a “Plasmonic ELISA” for the ultrasensitive detection of disease biomarkers with the naked eye (5). We are applying these biosensing approaches both in high throughput drug screening and to diagnose diseases ranging from cancer to global health applications.
Lotte Søgaard-Andersen obtained her M.D. and PhD in molecular biology from the University of Odense in Denmark. She moved to Marburg in 2004 as Director and Head of the Department of Ecophysiology at the Max Planck Institute for Terrestrial Microbiology.
Her research interests focuses on how bacterial cells process information to generate and regulate output responses such as adaptation, differentiation, growth and cell movement. Information processing is carried out by complex networks of signal transduction proteins. A challenging problem is to understand how these protein networks are organized in space and time to allow the ordered execution of these various tasks. We probe this question by studying signal transduction pathways and networks governing development, motility, cell polarity, and cell cycle in Myxococcus xanthus.
All natural cells display regulated gene expression and are spatially highly organized. Major strides have been made in synthetic biology to design and engineer circuits that control gene expression. In comparison, the design and engineering of circuits for the spatial organization of cells remain a central challenge. This deficit is, at least in part, due to our poor understanding of the mechanisms responsible for spatially organizing cells. Bacterial cells display polarity with many proteins localizing asymmetrically to specific subcellular regions. Moreover, several of these proteins localize dynamically and change their localization over time. For most of these proteins, changes in localization are intimately tied in with cell cycle progression. A comparatively simpler case of bacterial cell polarity is represented by motility proteins in the rod-shaped cells of M. xanthus that localize dynamically to the cell poles in a cell cycle-independent manner, i.e. during a cellular reversal motility proteins localizing to the lagging cell pole switch to the new lagging cell pole and proteins at the old leading pole switch to the new leading cell pole. This system for cell cycle-independent regulation of dynamic cell polarity is built around the small GTPase MglA, which functions as a nucleotide-dependent molecular switch, and its cognate GAP MglB. MglA/GTP and MglB bind to the leading and lagging cell pole, respectively and define the leading/lagging polarity axis in M. xanthus. In response to signaling by the Frz chemosensory system, MglA/GTP and MglB switch poles resulting in an inversion of the polarity axis. We use this system to understand design rules for circuits regulating dynamic cell polarity. Our work to characterize the components of the system as well as our efforts to establish this system as a module for regulation of dynamic cell polarity in other bacteria will be presented.
Tetsuro Toyoda was born in Tokyo, Japan, in 1968. He graduated from the Faculty of Pharmaceutical Sciences at the University of Tokyo in 1992, and obtained his PhD in 1997 from the same university. He started as a researcher at the Institute of Medical Molecular Design in 1997, and joined RIKEN as team leader in the Genomic Sciences Center in 2001. He became director of the RIKEN Bioinformatics and Systems Engineering Division when it was established in 2008.
His expertise is in bioinformatics and computer-aided rational design of biomolecules, including rational database-supported drug design based on protein structural information and rational genome design in synthetic biology for biomass engineering. He promotes Japan’s database integration projects as a member of several national database committees.
Biological engineering problems require innovative DNA designs. Once a DNA design problem has been defined, crowd innovation can be harnessed to explore solutions. We proposed the problem of formaldehyde detoxification in Arabidopsis thaliana, based on known enzymatic pathways from other organisms. In GenoCon, the first international rational genomic design contest, contestants designed DNA to introduce these pathways by codon optimization and addition of various cellular localization tags. As a competition, GenoCon presents challenges for rational design of DNA sequences to enhance plant physiology, using public data, followed by outsourcing experimental synthesis and biological assays. Participants designed DNA sequences on our system: a web-based platform for sharing life science data along with a scripting interface for DNA design. Outsourcees of experiments synthesize the designed DNA sequences, transform the DNA into Arabidopsis thaliana, and assay the function: in this case growth tolerance to formaldehyde. We quantitatively analyze the growth in the presence of formaldehyde; this analytical process deeply depends on the expertise of the physiology of interest and requires collaboration among physiological specialists and informaticians. GenoCon also educates young scientists as genome design specialists, and as a web bioinformatics activity, no time consuming and expensive experiments are needed to participate. This first GenoCon challenge had 66 entries including eight high school students. The designs used three different synthetic pathways and varied the cellular location of each enzyme with protein localization tags directing to the chloroplasts, the mitochondria, and the endoplasmic reticulum. Five designs including two high school students were selected as finalists. We assayed the performance of the designs, and found several that displayed dramatic formaldehyde tolerance at intermediate formaldehyde levels.
Kim Turk Križanec
ERA-Net project manager, representative of Slovenia in ERASynBio
Ministry of Education, Science and Sport of the Republic of Slovenia
Kathleen M. Vogel is an associate professor at Cornell, with a joint appointment in the Department of Science and Technology Studies and the Judith Reppy Institute for Peace and Conflict Studies. Vogel holds a Ph.D. in biological chemistry from Princeton University.
Prior to joining the Cornell faculty, Vogel was appointed as a William C. Foster Fellow in the U.S. Department of State’s Office of Proliferation Threat Reduction in the Bureau of Nonproliferation. Vogel has also spent time as a visiting scholar at the Cooperative Monitoring Center, Sandia National Laboratories and the Center for Nonproliferation Studies, Monterey Institute of International Studies.
Since 11 September 2001 there is growing national and international policy focus on the increasing threat of bioterrorism. Underpinning this policy focus is a dominant frame of discourse for how to consider biosecurity threats. This presentation will describe some of the key ideas comprising the dominant biosecurity discourse and contrast it with an alternative framing of the issues. To illustrate these different frames, this presentation will draw on examples from the field of synthetic biology that have generated security concerns. This presentation will discuss how the current dominant frame takes away attention from other important considerations for assessing the threat from emerging biotechnologies.
Susanne von Bodman
National Science Foundation
Dr Watu Wamae is an Analyst in the Innovation and Technology Policy team at RAND Europe since 2010. She is also a visiting fellow at the Open University and at the African Centre for Technology Studies. Prior to joining RAND Watu worked both in academia and government and has significant experience informing innovation strategy and policy. In her previous appointments she worked closely with governments at the national, regional and pan-African levels. Watu continues to inform policy making in Africa and is a member of the Technical Experts Group for the African Observatory on Science, Technology and Innovation, which a multidisciplinary team of five leading scholars and practitioners of science, technology and innovation policy. She is also involved in a number of research networks and is a board member of the African Network for Economics of Learning, Innovation, and Competence Building Systems whose main focus is to strengthen research capacity in Africa.
Wilfried Weber is Professor of Synthetic Biology at the University of Freiburg, Germany. Wilfried holds a diploma in biotechnology and, after a stay at Novartis Pharma, he joined Martin Fussenegger at ETH Zurich where he earned his PhD and started building up his research group.
Wilfried’s research focuses on combining synthetic biology with materials sciences to develop genetic switches and smart polymer systems to program mammalian cells by providing intracellular and extracellular cell-instructive cues. Wilfried is co-inventor of several patent applications and co-founder of the spin-off company Bioversys.
Plant and bacterial photoreceptors represent highly suitable tools for designing and constructing optically triggered switches for controlling genetic and biochemical processes in mammalian cells. We will show how these tools can be used to control mammalian cell function, either by applying genetically encoded optical tools or by synthesizing light-responsive extracellular matrices. We will show the latest generation of multi-chromatic expression control technology for the differential activation of up to three genes by illumination with light of different color. Capitalizing on these light-triggered photoreceptors we will show approaches for synthesizing biohybrid materials that serve as light-controlled adjustable extracellular matrix for providing mechanical and biochemical cues to mammalian cells. We will demonstrate how such synthetic biology-inspired biohybrid materials can be used for the remote-controlled administration of drugs at the example of one-injection-based vaccination regimes.
Jamey Wetmore is an Associate Professor at Arizona State University (US) with the Consortium for Science, Policy & Outcomes and the School of Human Evolution & Social Change. He is Associate Director for Engagement of the Center for Nanotechnology in Society and co-editor of “Technology and Society: Building our Sociotechnical Future” (MIT Press, 2008).
Much of his work focuses on developing new ways to reflect on technology and scientific research in order to improve our understanding of their effects and guide innovations toward socially desirable outcomes.
RT Hon David Willets MP
Xun Xu — the deputy director of BGI-Shenzheni — presided over experimental technology of molecular biology, information technology research and development. He devoted himself to bioinformatics research, including genome assembly and annotation research for plant genomic, genetic polymorphism research based on the re-sequencing. At the same time, he engaged in explorations and studies on molecular breeding in plants, single cell operation and other experimental techniques, and built the experimental platform for micro-sequencing of single cell. He was the head of the American Section as well as the Associate Researcher of the BGI-Shenzhen in 2011.
At present, he was the deputy director of BGI-Shenzhen. 18 papers were published in high-impact journal including nature and science until now, he first or co-first author for 8 of them, and have undertaken scientific research projects 7 items, including National Science and Technology department “973” project, “863” project and the Ministry of Agriculture “948” project.
Dr. Hal Alper is an Assistant Professor in the Department of Chemical Engineering at The University of Texas at Austin. His research focuses on metabolic and cellular engineering in the context of biofuel, biochemical, and biopharmaceutical production in an array of model host organisms. In the context of this work, Dr. Alper focuses on applying and extending the approaches of related fields such as synthetic biology, systems biology, and protein engineering.
Dr. Alper has published over 40 articles and has over 2100 citations with an h-index of 18. Dr. Alper is the recipient of the Camille and Henry Dreyfus New Faculty Award in 2008, the Texas Exes Teaching Award in 2009, the DuPont Young Investigator Award in 2010, the Office of Naval Research Young Investigator Award in 2011, the UT Regents’ Outstanding Teaching Award in 2012 and the 2013 Biotechnology and Bioengineering Daniel I.C. Wang Award.
Synthetic biology provides the means of designing novel parts to aid in the controlled, tunable, and regulated expression of individual genes, circuits, and pathways. Here, we describe recent advances in synthetic control of transcription by hybrid promoters in both Saccharomyces cerevisiae and the nonconventional yeast, Yarrowia lipolytica. These synthetic promoters are comprised of two modular components—the enhancer element and the core promoter element. We demonstrate that upstream activating sequences can serve as “synthetic transcriptional amplifiers” that can be used either individually or in tandem to tune and regulate gene expression. By utilizing such an approach, we can create libraries with ranges of over 400 fold in mRNA level, create the strongest known constitutive promoters, and synthetically impart strength and regulation traits to promoter elements. Second, we will discuss the synthetic design of expression cassettes and operons. Importantly, we measure and model the impact of 5’ UTR regions on translational control to design synthetic cassettes that have sustained, high-level expression regardless of cloning strategy. Finally, we discuss the impact of genetic context for synthetic parts—a particularly important aspect for characterization and predicable function. By synthetically altering upstream regions, terminator components, and promoter structure, defined and reproducible function can be obtained. Collectively, these results demonstrate novel approaches to synthetically alter and control gene transcription—a central goal of metabolic engineering and synthetic biology efforts. Thus, we conclude with specific applications of these tools for metabolic pathway engineering.
"Patrick" Yizhi Cai
“Patrick” Yizhi Cai received a bachelor degree in Computer Science in China, a master degree in Bioinformatics from University of Edinburgh in the UK, and a PhD in Genetics, Bioinformatics and Computational Biology from Virginia Tech in the USA. Cai has his postdoctoral fellowship under Jef Boeke in the Johns Hopkins University School of Medicine. Cai serves as a senior scientific consultant to Beijing Genomics Institute, and is the first Autodesk Distinguished Scholar.
Starting summer 2013, Cai will start his own research group at the University of Edinburgh with a prestigious Chancellor’s Fellowship, and his lab focus on Computer Assisted Design for Synthetic Biology, NeoChromosome design and synthesis in the yeast, and DNA assembly automation.
We propose a Gene Guard approach, “K-plex Integrated Safety Switches (KISS)”, rooted in the development of foundational genomic, regulatory and metabolic technologies. To demonstrate the generality of our approach and the prospect of extending safeguards to any microorganism, we present the coordinated development of KISS in both Escherichia coli and Saccharomyces cerevisiae, the best studied model prokaryote and eukaryote microorganisms, with natural and synthetic genomes. This combined approach assures the development of generic strategies for a wide range of microbes, and many aspects of it are even compatible with viruses. We designed five main KISS “SafeGuard Technologies” that act at the genetic, transcriptional, translational and metabolic levels, enabling us to deploy multiple GeneGuards for safety and isolation. By targeting different cellular processes in a multiplex fashion, our approach enables us to generically affect the function of one or more genes, nutrients or metabolites essential to microorganisms. Importantly, these SafeGuard Technologies can act individually or in any combination for multiplicative effectiveness. For example, engineered protein and/or RNA-based switches can be used to replace native regulatory mechanisms such that cell viability can be specifically linked to the presence of exogenous synthetic small molecules. Because any of hundreds of essential gene(s) can be re-engineered in this manner, we could increase the effectiveness of such a safety switch by multiplexing essential genes (e.g., histone genes in S. cerevisiae; guanylate and thymidylate kinase genes in E. coli and S. cerevisiae). The strong selections in place for essential gene function (viability) will allow assessment of the development of resistance to KISS to be rapidly assessed. If resistance is observed, mechanism(s) of resistance will be assessed. The nature of the design is such that it can readily be adapted to any microbe, multicellular organism or even viruses, any organism with one or more essential genes.
Yvonne Chen received her B.S. in Chemical Engineering from Stanford University and her Ph.D. in Chemical Engineering from the California Institute of Technology. She is currently a Junior Fellow in the Harvard Society of Fellows and a visiting research fellow at Harvard Medical School. Yvonne will join the Department of Chemical and Biomolecular Engineering at UCLA as an assistant professor in July 2013.
Her research interests focus on the application of synthetic biology and biomolecular engineering to the development of biological systems with real-world applications, particularly in health and medicine. Current research interests include the engineering of next-generation chimeric antigen receptors for adoptive T-cell therapy for cancer and the construction of synthetic signaling pathways to increase the safety and efficacy of tumor-targeting T cells.
T cells expressing tumor-targeting chimeric antigen receptors (CARs) have shown exciting promise in clinical trials, particularly in the treatment of B-cell leukemia. However, important challenges remain in the use of CAR-modified T cells, including off-target toxicity toward normal cells and susceptibility to mutational escape by targeted tumors. Due to a general lack of truly tumor-exclusive antigens, CARs typically target tumor-associated antigens that are also present on a subset of healthy cells, leading to on-target, off-tumor toxicity such as B-cell aplasia observed in patients treated with T cells expressing anti-CD19 CARs. Furthermore, patients who attain complete remission with anti-CD19 CAR-expressing T cells remain susceptible to relapse from the outgrowth of CD19- blast cells—i.e., mutational escape by tumor cells. One strategy to prevent mutation escape is to engineer CARs that recognize multiple antigen inputs and execute killing upon finding any one of the targeted antigens. Alternatively, CARs can be programmed to require the correct combination of input signals before triggering T-cell effector functions, thereby increasing targeting specificity. Here, we present an “OR-Gate” CAR that, when expressed in primary human T cells, efficiently lyse target cells expressing either CD19 or CD20, both of which are common markers of leukemic B cells. We demonstrate this dual-antigen targeting capability through quantitative measurements of target cell lysis and cytokine production. We will also present our designs for a “NOT-Gate” CAR and discuss its implications on our understanding of CAR signaling in relation to natural T-cell receptor signaling. Ongoing work focuses on widening the target differentiation response for the NOT-gate CAR and expanding the technology to additional antigen combinations for improved tumor-targeting specificity in T-cell immunotherapy.
Le Cong is from Beijing, China. He studied electronic engineering and biological sciences at Tsinghua University. He received his B.S., summa cum laude, in 2009, awarded the Tsinghua Grand Scholarship given to top 5 students out of all 13,915 undergraduates. Afterwards, he moved to U.S. to pursue his graduate degree at Harvard Medical School. He is co-advised by Drs. Feng Zhang and George Church.
He has been working on a number of projects from in situ sequencing, directed evolution, to genomic and epigenomic engineering, with a focus on developing new technologies to enable high-throughput genome engineering. Le has been working on Transcription activator-like effector (TALE) and CRISPR-Cas system based technologies and their applications. He has co-authored eight peer-reviewed papers in journals such as Science, Nature Biotechnology, etc., and was co-inventor on several related patent applications. He is interested in developing synthetic tools and utilizes them to understand human biology.
The integration of genetic, biochemical, and engineering techniques and vast amount of data from genome sequencing have enabled us to synthesize various types of biomaterial for engineering purposes and utilize the genetic information of different biological systems and organisms with unprecedented resolution. However the emerging atlas for the development and application of synthetic biology and bioengineering is both illuminating and perplexing due to the lack of powerful and precise tools to control biological systems at genome-scale, especially in mammalian systems.
Recent developments in cell-specific perturbation technologies are beginning to give researchers the ability to reverse engineer various biological processes and probing the properties of specific molecules within a biological circuits or cellular ecosystems. Yet the need for a true easy-to-design, fast-to-synthesize, low-cost, multiplexable, open-source genome engineering technology still persists. Our work focuses on two parts to further advance synthetic biological tools to bridge this gap between data generation and experimental tools:
- developing and testing technologies to support large-scale high-throughput genome engineering efforts based on Transcription Activator-like Effectors (TALEs) and CRISPR-Cas systems and
- integrating these tools with a variety of readout methods for modeling biological processes and developing synthetic pathways and circuits for applications in a variety of organisms.
This transforming technology platform will likely improve our understanding and control of the complex biological pathways and circuits within both prokaryotic and eukaryotic systems, leading to potential new synthetic biology applications in basic biology and industrial-scale bioengineering, as well as advance the field of translational research by providing powerful tools to the research community for developing novel therapeutics to improve human health.
John Dueber received his B.S. in Biochemistry from the University of Delaware in 1999 and Ph.D. at UCSF in 2005 under the mentorship of Prof. Wendell Lim. He then was a QB3 Distinguished Fellow with Profs. Jay Keasling and Adam Arkin until 2010.
Currently he is an Assistant Professor at U.C. Berkeley in the Bioengineering department and a member of the Energy Biosciences Institute. The Dueber lab’s research interests mainly focus on engineering strategies for increasing control and improving performance of multi-enzyme pathways – both signaling and metabolic.
Engineering high-flux metabolic pathways often results in undesired crosstalk with cellular factors of the production host. These could be losses of metabolites to competing pathways, accumulation of toxic intermediates, allosteric regulation, protein degradation, and non-optimal enzyme activity at cytosolic pH or redox state. We are following lessons from eukaryotic evolution to build a synthetic organelle capable of segregating engineered metabolism from the native biochemistry in the cytosol. Towards this, we are repurposing the peroxisome as this organelle is not required for S. cerevisiae viability provided fatty acids are not used as a sole carbon source. This organelle varies dramatically across fungi species with the majority of the cellular volume being occupied by the peroxisome in yeasts such as Hansenula polymorpha and methanol-induced Pichia pastoris, suggesting that higher capacity peroxisomes can be genetically engineered. We have been able to improve the efficiency of a seldom-used targeting sequence that allows us to clear out the majority of the native luminal protein while importing multiple heterologous enzymes in the folded state. Additionally, we have successfully implemented a strategy for redirecting plasma membrane transporters to the peroxisome membrane. We are currently in the process of demonstrating that flux can be controlled through a branched pathway to control which product is synthesized. Ultimately, we endeavor to alter the environment of this organelle (e.g., redox state, pH, etc.). to enable biochemistry that would not be feasible in the cytosol.
Maiko Furubayashi is a PhD student at Chiba University under the supervision of Dr. Daisuke Umeno, and serves as a JSPS Research Fellow. Her research interest is on testing “synthetic” approach to inquire how metabolic pathways evolve new functions and become more specialized. Specifically, she is now working on the construction of long step pathways for non-natural carotenoids and terpenoids.
Synthetic biology aspires to construct novel metabolic pathways to useful, sometimes unnatural compounds. In extending natural pathways in novel directions, pathway engineers usually rely on the promiscuous activities (the ability to accept alternative substrates and/or synthesize alternative products) of recruited or mutated enzymes. However, the promiscuous enzymes that enable molecular discovery can generate hyperbranched pathways that preclude specific production of the target novel product. Here, we assembled a six-enzyme pathway in Escherichia coli for the 15-step synthesis of C50-astaxanthin, a non-natural purple carotenoid, by the judicious pairing of laboratory-engineered promiscuous enzymes. The initial combination of promiscuous enzymes encompassing the six desired biochemical functions resulted only in a mixture of non-target carotenoids. We then evolved variants of the first two pathway enzymes, isoprenyl diphosphate synthase (FDS) and carotenoid synthase (CrtM), with shifted specificity ranges. The combinatorial pairing of the selected variants resulted in specific production of C50 carotenoid backbones. The specific C50 backbone pathway enabled the directed evolution of the third enzyme, carotenoid desaturase (CrtI), to synthesize C50-lycopene. Coexpression of three downstream promiscuous enzymes (CrtY, CrtW and CrtZ) enabled the further extension of the C50 carotenoid pathway. The resultant pathway to C50-astaxanthin is both highly efficient and selective, despite containing not a single catalytically specific enzyme. We believe our results and analysis provide a framework for understanding how complex and precise biosynthetic networks can be built out of imperfect biosynthetic parts, either by synthetic biologists or natural evolution.
Daniel Bryan Goodman is a PhD candidate in the Harvard-MIT Division of Health Sciences and Technology and in Professor George Church’s lab at the Wyss Institute of Biologically Inspired Engineering. Daniel is using microarray-based DNA synthesis technologies to design, assemble, and test thousands of genetic elements, genes, and gene networks in parallel.
Prior to joining the Wyss Institute, he was a Whitaker Bioengineering Fellow at The University of Cambridge in the United Kingdom. Daniel received his B.S. in Bioengineering from the University of California at San Diego, where he worked on comparative genomics and proteomics with Prof. Pavel Pevzner and Prof. Phil Bourne.
The unpredictability of gene expression hinders our ability to engineer biological systems. A standardized library of well-characterized regulatory elements offers a potential solution only if such elements behave predictably when combined. To answer this question, we synthesized 27,000 combinations of common promoters, ribosome binding sites, and N-terminal coding sequences and simultaneously measured DNA, RNA, and protein levels from the entire library. Using a simple additive model, we found that RNA and protein expression were within 2x of predicted levels 80% and 64% of the time respectively. This large dataset allowed quantitation of global effects. Surprisingly, we found that the use of rare codons at the N-terminus strongly increases expression compared to common codons. Additionally, we measured how GC content and secondary structure affect translation efficiency and how translation rate alters mRNA stability. Even after accounting for the effects of these variables, unexplained severe outliers remain that hinder the use of prediction and standardization in large-scale genetic engineering projects. The ease and scale of our DNA synthesis approach indicates that it is feasible to design and screen large libraries for desired behavior.
Joao Guimaraes received his B.Eng. in Computer Science and Systems Engineering from the University of Minho, Portugal. In 2009, he started his Ph.D. in Computational Biology supervised by Adam Arkin at the University of California, Berkeley and Miguel Rocha at the University of Minho, Portugal.
As part of his graduate studies, he was also a researcher at the BIOFAB: International Open Facility Advancing Biotechnology. The main focus of his graduate studies has been the development of computational models to understand gene regulation in natural systems and to aid engineering synthetic genetic elements leading to a predictable control of gene expression in bacteria.
The practice of engineering biology now depends on the ad hoc reuse of genetic elements whose precise activities vary across changing contexts. Methods are lacking for researchers to affordably coordinate the quantification and analysis of part performance across varied environments, as needed to identify, evaluate and improve problematic part types. We developed an easy-to-use analysis of variance (ANOVA) framework for quantifying the performance of genetic elements. For proof of concept, we assembled and analyzed combinations of prokaryotic transcription and translation initiation elements in Escherichia coli. We propose a new statistic, biomolecular part “quality,” for tracking quantitative variation in part performance across changing contexts. We used this metric to identify design flaws leading to unpredictable behavior, and motivate the engineering of improved genetic elements that can reliably express sequence distinct genes across a 1000-fold observed dynamic range and within 2-fold relative target expression windows with ~93% reliability. Lastly, we characterized a set of transcription terminators with widely variable efficiencies; used co-transcriptional folding simulations to identify context effects leading to deviant behavior; and developed a sequence-activity relationship model for this class of elements. In summary, we developed a gene expression control system comprised of transcription and translation initiation elements, and transcription terminators with predictable performance that enable reliable forward engineering of gene expression at genome scales.
Patrick Guye is currently a Postdoctoral Research Fellow at the Synthetic Biology Center (Biological Engineering) in the lab of Ron Weiss at MIT. He received his Diploma in Molecular Biology and his Ph.D. In Molecular Infection Biology from the Biozentrum at the University of Basel in Switzerland studying host-pathogen interactions.
Spearheading Synthetic Biology in human stem cells, his current research interest is to understand and harness the engineering principles of our own development. Emergent, multicellular, highly plastic and self-organizing systems keep his clock ticking. With a focus on regenerative medicine, embryonic development and tissue engineering, he is developing methods and tools to generate specialized cell types, tissues and organs from stem cells.
Induced pluripotent stem (iPS) cells have a tremendous potential for personalized and regenerative medicine, developing novel disease models or investigating the engineering rules of our own development. While the generation of such personalized stem cells became routine in the last years, it remains a challenge to precisely control their differentiation to specific cell types, tissues or organs. We have developed tools to rapidly construct and integrate site-specifically large gene circuits into stem cells where they measure protein and microRNA levels and direct their differentiation. In doing so we demonstrate generation of definitive endoderm, specific neural cell types and mesodermal derivates from human iPS cells. We propose that genetically engineering stem cells by applying principles from Synthetic Biology is a powerful emerging technology with a wide range of uses.
Jennifer Hallinan completed a First Class Honours degree in molecular biology at the Australian National University, followed by a PhD in computer science at the University of Queensland. She was a Group Leader at the Institute for Molecular Biosciences at the University of Queensland before moving to the United Kingdom in 2006 to take up a position with the Centre for the Integrated Systems Biology of Ageing and Nutrition at Newcastle University.
Jennifer is currently a lecturer in bioinformatics and synthetic biology at Newcastle. She is interested in the application of computational intelligence techniques to the design and analysis of synthetic genetic circuits.
Quorum communication is the process by which bacteria communicate, allowing them to modify the transcriptome in response to the nature and number of other bacteria in their environment. In Gram-positive bacteria, quorum communication commonly occurs via the production and sensing of small peptides by two-component systems, each of which consists of a membrane-bound response regulator and a protein kinase which triggers a phosphorylation relay leading to the activation or repression of suites of genes. The engineering of quorum communication systems permits synthetic biologists to manipulate the behaviour of entire populations of bacteria as well as that of individual cells. In synthetic biology, as in electrical engineering, we need to be able to control the receiver response characteristics in order to ensure that the system of which they are part performs in a predictable, desired manner. In this work we apply computational design approaches, incorporating an evolutionary algorithm, to the modification of the receiver response characteristics of the SpaR/K two-component system of B. subtilis. This system produces and responds to subtilin, a lantibiotic produced by only some strains of the bacterium. The evolutionary algorithm builds simulateable models of the subtilin system using Standard Virtual Parts (SVPs), which can be swapped in and out of the model. The algorithms draws upon our extensive repository of SVPs: small SBML models of biological parts such as promoters, RBSs and CDSs. Both the kinetic parameters and the circuit topology can be modified. Manipulation of the subtilin system will allow us to control the behaviour of a mixed bacterial population. We demonstrate the application of our computational design system to the production of subtilin receiver response curves with a variety of shapes different from the sigmoid response of the wild type receiver.
Paul is a Biological Engineer with diverse research experience ranging from mapping chlorophyll biosynthesis pathways to designing and building synthetic virus genomes. He started off his science career at the University of Alberta (Canada). After achieving an Honors B.Sc. in Biochemistry in 2003 Paul took a year off and traveled the Pacific. During that time he worked on natural products chemistry at the University of Queensland in Brisbane Australia.
Paul started his Ph.D. in the Beatty Lab at the University of British Columbia in 2004. While at UBC Paul discovered that a photosynthetic bacteria called Rhodobacter sphaeroides was capable of re-routing its chlorophyll biosynthetic machinery around a blockage to generate a new type of chlorophyll. Paul is currently focused on building viruses to understand them and pioneering a synthetic biology method called negative genomics.
Our capacity to read and write DNA has outpaced our ability to design useful and predictable DNA sequences. Synthesizing genomes could enable powerful new approaches to biological discovery, however, due to the overwhelming complexity of biological systems, most designs have largely recapitulated natural sequences. To advance synthetic genome design methods we focused on the 5.4 kb X174 bacteriophage genome because it is: (1) small enough to enable rapid prototyping of new designs, and (2) complex, displaying an intricate architecture encoding 11 overlapped genes spanning all reading frames. Two approaches were used to reduce the complexity of the X174 genome while addressing important biological questions. Gene overlaps are common in nearly every genome and their functional significance is controversial. We investigated the origin of gene overlaps by designing a fully decompressed synthetic genome ‘X174.1f’, that contained no overlapping genetic elements. We describe our genome design, construction, and successful redeployment. Phenotypic comparisons between wild type and X174.1f showed there were minimal observable differences between the two viruses, and no essential information in the gene overlaps. Additionally, the results suggest that gene decompression is a viable approach to reducing genome complexity. Secondly, we developed a method of genome simplification called ‘negative genomics’ that seeks to address a fundamental question of genome annotation: at what point can we confidently say we have found all the genes? To establish all potential open reading frames (ORFs), other than the 11 known genes, we searched the X174 genome using computational gene-finding tools. Finding 85 candidate cryptic ORFs we designed a new genome, called ‘X_clean’, with 88% of these cryptic ORFs erased via synonymous changes. Testing the prototype X_clean genome revealed that it is capable of forming plaques but is phenotypically different from wild type, suggesting previously undiscovered functions associated with the disrupted ORFs.
Premkumar Jayaraman received his Bachelor’s degree in Industrial Biotechnology, 2006 from Anna University, Chennai, India. He completed his Master’s degree in Biomedical Engineering with the Certificate of Excellence 2008 for MAE MSc Top Graduates award, at Nanyang Technological University (NTU), Singapore after which he went on to complete his PhD from Biomedical and Engineering Research Centre in 2012 at NTU, Singapore.
He joined the School of Chemical and Biomedical Engineering, NTU as a postdoctoral researcher in 2012. His current research is focused in modeling a virtual cell to evaluate the protein synthesis and host effects by different topology synthetic gene circuits.
Given an unprecedented ability to manipulate cells through synthetic biology to address problems in areas such as energy, health and environment, currently we still face challenges in perfecting an engineered system to our desire. The daunting challenges confronted by the biological circuit engineers are, complexity, unpredictability and variable behavior of the host system that contains the engineered designs. In addition, the practice of trial-and-error synthetic circuit designs and in vitro evaluation are laborious and time-consuming. Currently, models able to predict host-dependent circuit functions and burden on the host-cell environment accounting energy consumption, resource uptake and cellular processes are lacking. The insights from those models could be used to engineer and fine-tune the synthetic gene circuit’s components and parameters for optimal protein production and reduced host-burden effects. To this end, we propose a novel E. coli virtual cell for predicting the behavior of different synthetic biological devices in silico. The model incorporates three key ‘cellular processes’ and its components: (i) ‘nutrient uptake’ to evaluate energy compensation, (ii) ‘growth’ to determine macromolecular composition, pools of cellular machinery and monomer synthesis, and (iii) ‘replication’ of its components under regulation. Our preliminary results demonstrate that our model is able to reproduce the number and concentration of proteins, RNAs and cellular machineries of the host system at varying growth rates. We will present the development of this model considering how glucose as the sole energy source under regulation, a single virtual cell allocates energy and resources in synthesizing RNAs, proteins including machineries and monomers, initiation until completion of replication (doubling time) by monitoring growth rate and timing cellular processes. Looking forward, the work described here is a step towards predicting synthetic circuits behavior and its host-effects.
Kil Koang Kwon
Kil Koang Kwon received his BS/MS at the Department of Microbial Engineering at Konkuk University in South Korea. He is currently completing his PhD in the Department of Chemical & Biomolecular Engineering at Korea Advanced Institute of Science and Technology (KAIST). He is also working at the Biochemicals & Synthetic Biology Research Center in Korea Research Institute of Bioscience & Biotechnology (KRIBB).
Enzyme engineering and synthetic biology are his main research interests, so he is currently working on the applications of genetic circuits along with protein engineering.
Large-scale screening of enzyme libraries is essential for the developments of cost-effective biological processes, which will be indispensable for the sustainable green chemistry. Here, we report a single cell based screening using a genetic circuit that enables the cell to respond quantitatively to aromatic molecules, which is released from substrates by the activity of target enzymes. The genetic circuit consists of two AND gates where the first one is turned on by a target enzyme and a substrate with an aromatic side chain. The aromatic molecule, in turn, could be an input signal of the second AND gate and it is turned ON by a sensor protein which initiates the transcription of a GFP fluorescent reporter gene after the recognition of aromatic molecules. We used a bacterial regulator, dmpR, as the phenol sensor protein which could be replaced by other effector binding genes such as tbuT if the effector is toluene. In cells harboring this genetic circuit, diverse enzyme activities, such as those of tyrosine phenol-lyase, lipase, cellulase, and methyl parathion hydrolase, were detected by the fluorescence emission when phenol- or nitrophenol-derivatized substrates of these enzymes were supplied. Along with these cells, a high throughput flow cytometry was successfully used to isolate a novel phosphatase from a metagenome library derived from tidal flat sediment using phenyl phosphate as a substrate. Our result shows that the genetic circuit provides a widely applicable tool for high throughput and quantitative screening of diverse activities from large-scale enzyme libraries. In addition, quantitative part characterization of the circuit by analyzing their fluorescence changes would provide useful information for further plug and play circuit design.
Joshua N. Leonard, Ph.D. is an Assistant Professor of Chemical and Biological Engineering in the McCormick School of Engineering and Applied Science, the Robert H. Lurie Comprehensive Cancer Center, and Chemistry of Life Processes Institute at Northwestern University. Leonard also co-directs a cluster in Biotechnology, Systems, and Synthetic Biology and is a founding mentor of NU’s iGEM team. Leonard received a BS and PhD in chemical engineering from Stanford University and the University of California, Berkeley, respectively, and trained in immunology as a postdoctoral fellow at the National Cancer Institute (NIH).
The Leonard group is committed to enabling design-driven medicine by pairing systems biology and synthetic biology. They develop novel technology platforms and “parts” for engineering mammalian cell-based devices and apply these capabilities to probe and program immune function, enabling novel treatments for cancer, more effective vaccines, and diagnostics for global health.
The ability to engineer customized mammalian cellular functions would enable the construction of sophisticated cell-based therapeutics and transformative tools for fundamental biological research. Such capabilities could overcome persistent barriers to treatment in applications ranging from cancer immunotherapy to regenerative medicine. Synthetic biology provides such an approach for building novel cellular functions from the bottom up, and the “toolbox” of biological parts that operate in mammalian cells is rapidly expanding. To date, however, we lack the ability to construct synthetic cell-based biosensors that detect and respond to exclusively extracellular cues. Because many species of biological relevance, including cytokines, chemokines, cell-surface antigens, and many pathogens are exclusively extracellular, engineering cell-based devices that interface robustly with host physiology will require sensors for extracellular species. To address this need, we have developed a Modular Extracellular Sensor Architecture (MESA). By coupling cell surface sensing modalities to orthogonal intracellular signaling mechanisms, this platform enables the engineering of novel cellular functions such as multiparametric evaluation of extracellular cues. Finally, I will also discuss our application of these capabilities to probe interactions between cancer and the immune system, and to develop safe and effective therapies that harness the immune system to eradicate cancer.
Sierin Lim obtained both her B.S. and Ph.D. degrees from University of California, Los Angeles (UCLA) in Chemical Engineering and Biomedical Engineering, respectively. She joined Nanyang Technological University as Assistant Professor in the School of Chemical and Biomedical Engineering at the end of July 2007 after a 2.5-year postdoctoral research at University of California, Irvine (UCI).
Dr. Lim’s research focuses on the design, engineering, and development of hybrid nano/microscale devices from biological parts by utilizing protein engineering as a tool. Her main interests are in self-assembling protein-derived nanocapsules and photosynthetic biological materials. The project scopes range from understanding the self-assembly mechanism of the nanocapsules to their applications as theranostic carriers and nanoparticle synthesis template to improvement of electron transfer efficiency in a photosynthetic electrochemical cell.
Synthesis of monodispersed nanoparticles that are free from aggregation is particularly challenging using chemical methods. E. coli has been engineered to synthesize iron nanoparticle by increasing the metal intracellular sequestration and production of protein cage as the biological template. The protein cages are formed by self-assembly of multiple subunits forming highly uniform hollow spherical cage structures of nanometer size. Expression of both the FeoB iron transporter and ferritin under inducible promoter results in the production of approximately 10 mg of protein cage/liter of culture; loaded with up to 200 Fe/cage forming an iron core of ~8 nm. This loading can be optimized in vitro with the highest loading observed at 7000 Fe/cage. Besides serving as template, the protein cages have been shown to assist the solubilization and prevent the aggregation of the nanoparticle. Further modifications of the protein cages allow tailoring of its function as carriers for therapeutic and diagnostic agents. Due to their proteinaceous nature, the protein cages allow facile modifications on its internal and external surfaces, as well as the subunit interfaces. Modifications on the internal and the external surfaces allow conjugation of small molecule drugs or contrast agent and targeting ligands, respectively. The subunit interaction is of special interest in engineering triggered release property onto the protein cage. Applications of these protein cages as molecular carrier with triggered release capability will also be described.
Andreja Mjerle is a member of the Laboratory of Biotechnology at the National Institute of Chemistry in Ljubljana (Slovenia). She has long-standing expertise in synthetic biology as a member of Slovenian teams that have successfully competed in iGEM in 2006-2012. Her doctoral thesis in 2001 was in the field of innate immunity. She is a coauthor of an international patent on antimicrobial peptides.
Her current research interests focus on genetic logic gates and switches in mammalian cells and the development of a system for treatment of viral infections. In addition to research, she has a strong record of working with undergraduate and graduate students of the University of Ljubljana.
Electronic computer circuits consist of a large number of connected logical gates of the same type, such as NOR or NAND, which can be easily fabricated and which can implement any logical function. In contrast, transcription factors as the biological mediators of the cellular logic act on the whole set of binding sites within each cell. The complexity of designable genetic regulatory circuits is therefore limited by the availability of orthogonal transcription factors. The diversity of modular TAL (transcription activator-like) DNA binding domains is almost limitless. Here, we introduce designed orthogonal NOR gates based on TAL repressors as the universal scalable logical functions. Binding site for the designed TAL repressors were positioned upstream of the promoter, which decoupled the effect of any particular sequence on the transcription level variability. We implemented all 16 two-input logical functions within mammalian cell from combinations of TAL repressor-based NOR gates. According to Alan Turing the universal computing machine must be able to accept as input data values as well as instructions that define which logical functions should be performed on those data values. We constructed a genetic logical circuit composed of NOR gates, where one input is used to select execution of either AND or OR function over the two data inputs, demonstrating the principle of an universal biological computation device in mammalian cells. Biological genetic networks employing orthogonal designed NOR gate can therefore be used to implement in principle any logical function within mammalian cells to engineer a complex cellular response.
Piers D. Millett is Deputy Head of the Implementation Support Unit for the Biological Weapons Convention (BWC) housed in the UN Office for Disarmament affairs in Switzerland. He trained originally as a microbiologist and is a Chartered Biologist in the UK. He has a doctorate from the University of Bradford (UK) on the past present and future of anti-animal biological warfare, which focused heavily on the impact of developments in the life sciences on biological weapons.
He is widely published on issues related to preventing the acquisition and use of biological weapons and is a regular speaker at conferences around the world. Piers is also a member of the Transitional Board of Directors of the International Federation of Biosafety Associations, and a founding member of the Safety Committee of the International Genetically Engineered Machines Competition (iGEM).
The SB community, throughout its history, has successfully engaged with the societal implications of their work. Efforts by the community have been much heralded and have been held up as an example to other scientists. Community work in addressing security concerns has received particular attention and yielded concrete results. Much has been accomplished but now is not the time for complacency. Security efforts could still unduly restrict the promise of SB. Modern approaches to biology also pose distinct challenges to traditional security approaches. Often overlooked, SB also provides new opportunities to counter deliberate disease and the misuse of the life sciences. This presentation explores, through specific examples, emerging risks to and from synthetic biology from the security sector as well as opportunities for addressing them. Better balancing science and security interests will be a major theme of international policy and public discussions over coming years as focus on ‘Dual-Use Research of Concern’ expands from a limited set of influenza research projects to biology and biotechnology more broadly. This presentation reviews three relevant international process of particular importance to the SB community: the intersessional programme of the Biological Weapons Convention, focusing in particular on opportunities to influence international policy making; relevant work of the World Health Organization, including February 2013 meeting on Dual Use Research of Concern on Current Issues and Innovative Solutions; and the work of the Temporary Working Group on Convergence of Biology and Chemistry of the Scientific Advisory Board of the Organization to Prohibit Chemical Weapons.
Ron Milo is Assistant Professor in the Department of Plant Sciences at the Weizmann Institute of Science.
After a Bachelor degree in Physics and a Master’s in Electrical Engineering, I became mesmerized by living matter. My PhD at the Weizmann Institute dealt with building blocks of biological networks and I then tried to understand evolutionary adaptations as a Fellow at Harvard Medical School Department of Systems Biology.
Today, my lab members and I are passionate about trying to understand the cellular highways of energy and carbon transformations known as central carbon metabolism in quantitative terms. We employ a combination of computational and experimental synthetic biology tools. My research efforts combine three main directions: (1) Understanding the structure and logic of central carbon and energy metabolism in quantitative terms; (2) Synthetic metabolic pathways for carbon fixation; (3) Novel tools facilitating accurate, accessible and collaborative quantitative cell biology.
Protein levels are a dominant factor shaping natural and synthetic biological systems. While proper functioning of metabolic pathways relies on precise control of enzyme levels, the experimental ability to balance the levels of many genes in parallel is a major outstanding challenge. Here, we introduce a rapid and modular method to span the expression space of several proteins in parallel. By combinatorially pairing genes with a compact set of ribosome binding sites we modulate protein abundance by several orders of magnitude. We demonstrate our strategy by using a synthetic operon containing fluorescent proteins to span a three-dimensional color space. Using the same approach we modulate a recombinant carotenoid biosynthesis pathway in E. coli to reveal a diversity of phenotypes, each characterized by a distinct carotenoid accumulation profile. In a single combinatorial assembly we achieve a yield of the industrially valuable compound astaxanthin 4-fold higher than previously reported. The methodology presented here provides an efficient tool for exploring a high-dimensional expression space to locate desirable phenotypes.
Evan Olson is an Applied Physics PhD student in Jeff Tabor’s Bioengineering Lab at Rice University. Evan graduated from Central College in Iowa where he studied Physics, Mathematics, and Computer Science. In the Tabor lab, he has extensively characterized two bacterial light-sensing systems using the Light Tube Array (LTA), a custom apparatus which he designed and built. The LTA can generate up to 64 independently programmed light environments for cultures grown in a standard culture tube format.
This hardware solution enabled Evan to develop a standardized experimental workflow and to collect a large quantity of dynamical gene expression data. Using this data, he constructed quantitatively-predictive light-input/gene-expression-output models of both light-sensing systems. These models have enabled pre-computation of light programs which result in precise control of expression dynamics. Evan is now working to develop an optically-controllable continuous culture apparatus with fluorescence readouts which will enable long-timescale online control of light-sensing systems.
We have utilized both the red/green-sensing CcaS/CcaR and red/dark-sensing Cph8/OmpR two component systems (TCSs) to achieve precise, quantitative control of gene expression dynamics in E. coli. First, we have constructed a programmable array of light emitting diodes (LEDs) that allows calibrated dosing of different colors of light in any desired temporal pattern in up to 64 standard tubes of growing cells. We demonstrate for each TCS that the application of different activating to inactivating light ratios allows us to set a desired analog gene expression level. By shining light ratios in a time-varying sequence, we can then drive cells to move between desired analog expression levels without adjusting the growth media. Gene expression is reported by fluorescent proteins and single-cell data is acquired from each culture via flow cytometry. Our observations of cells grown in a variety of time-varying light sequences are well described by a phenomenological model whose kinetics and steady-state levels are determined by the illumination intensities. After calibrating the parameters of the model for each system with a dataset of gene expression time-courses under a variety of illumination patterns, the model has successfully predicted light control sequences that drive each TCS to generate arbitrary gene expression time-courses including linear ramps, accelerated steady-state switching, and sine waves of varying amplitude and period. Furthermore, we have under development a dual-input system which allows for the simultaneous control of both TCSs. This level of quantitative, temporal control of gene expression would be extremely difficult to achieve with traditional modes of gene regulation. Utilizing optogenetic devices, researchers can more readily adapt well-developed approaches for system identification, characterization, and control to biological systems, helping to make biology more engineerable. Thus, as it has in neurobiology, the precise perturbative nature of optogenetic tools therefore stands to contribute significantly to systems and synthetic biology.
Darren Platt heads the Automation and Computing Department at Amyris, which handles computation and robotics from strain design and construction through to high throughput measurement and fermentation. He has worked extensively in the sequencing field beginning with early human genome work at the Sanger Institute. After leading computing at the DOE Joint Genome Institute investigating diverse environmental sequencing including Neanderthal samples, he spent time in the personal genomics field as Director of Research at 23andMe before finally settling on yeast as the preferred sequencing target.
He developed a process for rapid deconvolution of mutagenesis hits in yeast at Amyris using next gen sequencing. More recently he authored the Genotype Specification Language (GSL) which is used in house at Amyris for advanced strain design. His current research interests include higher level design languages for synthetic biology including porting designs across species.
Denovo assembly and annotation of genomes has historically required the resources of large genome centers, custom software pipelines and expensive dedicated compute clusters. Taking advantage of advances in sequencing and software we have built an engineering oriented genome annotation pipeline with an emphasis on identifying standard parts that an engineer needs to rapidly engineer a new chassis. We have substituted a peer to peer architecture and cloud computing for traditional, IT-intensive compute clusters. The annotation process focuses on finding core canonical gene sets, flagging any species specific irregularities in those systems rather than characterizing the eccentricities of a specific organism. Our goal is to generate a set of standard promoters, loci, pathway parts and codon usage patterns from raw next generation sequencing data within hours of DNA sequencing. The output formats are tailored to work directly with our Genotype Specification Language (GSL). Coupled with a pathway design of interest we envisage a novice using GSL to translate a general pathway design into species specific parts within a day of sequencing a candidate microbial chassis
Arthur Prindle is a graduate student with Jeff Hasty at the University of California San Diego. His long-term research interests involve exploring novel microbial behaviors, distilling their design principles, and applying them toward new avenues in biotechnology.
Arthur was introduced to synthetic biology at Caltech (B.S. 2009) while doing his senior thesis with Richard Murray.
Bacto-engineering: from biopixels to cancer In many respects, bacteria are an ideal design platform for synthetic biology. They are small, extremely hardy, inexpensive to maintain, reproduce quickly, and comprise a vast array of species with unique properties. An expanding future landscape of integrated synthetic biology will utilize the native networks of diverse microbial species in concert with our own engineered gene circuits. In this talk, I will primarily describe an LCD-like array of colony “biopixels” that collectively report the concentration of a target compound with a frequency-encoded signal. These synchronous oscillations are maintained across populations as large as 13,000 colonies over centimeter length scales. Multi-scale coordination is achieved by layering 2 modes of communication – local quorum sensing and global redox signaling that utilizes the native aerobic response network. I will also describe several snapshots of recent work edging toward the clinical arena. We show that existing genetic circuits function equivalently in clinically-relevant hosts, and develop an experimental approach to study their in-vivo performance using mouse models of cancer[3, 4]. This platform is enabling work toward therapeutic applications, where we are engineering oral probiotics for instrument-free cancer diagnostics. 1. Prindle, A., et al., A sensing array of radically coupled genetic ‘biopixels’. Nature, 2012. 481(7379): p. 39-44. 2. Prindle, A., et al., Genetic Circuits in Salmonella typhimurium. ACS Synth Biol, 2012. 1(10): p. 458-464. 3. Danino, T.*, Prindle, A.*, et al., Measuring growth and gene expression dynamics of tumor-targeted S. typhimurium bacteria. [In Review], 2013. 4. Danino, T., et al., In Vivo Gene Expression Dynamics of Tumor-Targeted Bacteria. ACS Synth Biol, 2012. 1(10): p. 465-470. 5. Danino, T.*, Prindle, A.*, et al., Oral probiotics for instrument-free cancer diagnostics. [In Preparation], 2013.
Ingrid received her Ph.D. in Microbiology in 2012 and is currently a Senior Research Fellow in the lab of Dr. David Baker at the University of Washington in Seattle, WA. Her research interests lie in computer-assisted design and engineering of biological molecules in order to generate new molecules that demonstrate beneficial characteristics. In 2008, Ingrid founded the University of Washington’s iGEM team, and acted as instructor for the team through 2011.
Her current research goal is to engineer and develop the enzyme KumaMax as an oral therapeutic for celiac disease, advancing work that began as an iGEM project by Washington’s 2011 team. She and several others have recently founded a company, Proteus Biologics, based on this technology. Ingrid is the recipient of an ARCS Foundation scholarship, an NSF Graduate Research Fellowship, and a University of Washington Commercialization Fellowship.
The ability to rationally design enzymes to specifically combat certain diseases, such as celiac disease, has the potential for tremendous advances in medicine. Celiac disease is characterized by intense abdominal pain, malnutrition, and serious illness in 1-2% of the population upon ingestion of dietary gluten. The basis for this disease is an inflammatory immune response to incompletely digested gluten peptides in the intestine. To combat celiac disease, we first identified an enzyme that demonstrates some of the desired properties for an oral therapeutic to treat this disease, and then used advanced computational protein design tools based on the Rosetta Molecular Modeling Suite to engineer the enzyme to harbor the properties that it was lacking. The resulting enzyme, called KumaMax, will break down gluten in the stomach before it can elicit an immune response in the intestine. KumaMax demonstrates all of the characteristics required as an oral therapeutic for celiac disease: stability and activity in the conditions of the human stomach, specificity for gluten protein, and easy production and purification methods. This enzyme is capable of breaking down over 97% of an immunogenic peptide derived from gluten in gastric conditions in less than an hour, demonstrating its potential for use as an oral enzyme therapeutic.
Ithai Rabinowitch studied Industrial Engineering at Tel Aviv University, then switched to neuroscience, carrying out a PhD at the Interdisciplinary Center for Neural Computation at the Hebrew University of Jerusalem, under the supervision of Prof. Idan Segev. His work consisted of computational modeling of the effects of homeostatic synaptic plasticity, a relatively slow and compensatory form of plasticity, in dendritic branches, the intricate tree-like structure stemming from neocortical neurons.
Ithai next embarked on a postdoc in Bill Schafer’s lab at the MRC Laboratory for Molecular Biology, Cambridge, UK, where he worked on natural and artificial modifications of neuronal connectivity in the nematode C. elegans and on combining mathematical modeling with neuroimaging to investigate the C. elegans nose touch circuit. Ithai is currently a postdoc in Millet Treinin’s lab at the Hebrew University of Jerusalem, continuing his work on artificial neural circuit connections and on cross-modal plasticity in C. elegans.
The beautiful field of synthetic biology is successfully modifying, converting or plainly reinventing cellular and molecular processes, with the aim of improving our understanding of biology, and perhaps even improving biology. We wished to adopt the perspective and principles of synthetic biology to neuroscience, targeting neuronal connectivity rather than genetic interactions, and reprogramming whole animal behavior rather than cellular function. The fundamental building blocks of neural circuits underlying neuronal connectivity are synapses. In order to artificially modify synaptic connectivity we sought to introduce a new synapse between adjacent neurons in an existing neural circuit. However, inserting heterologous chemical synapses into a circuit would be difficult due to their enormous complexity and hundreds of constituent proteins. In contrast, electrical synapses, or gap junctions, consist of as little as one protein type. Moreover, the molecular constituents of vertebrate and invertebrate gap junctions belong to completely distinct protein families: connexins are exclusive to vertebrates and innexins to invertebrates. Importantly, while proteins from the same family can interact to form heterotypic gap junctions, no compatibility has been found between connexins and innexins. Thus, we reasoned that connexins expressed heterologously in neurons of the invertebrate nematode C. elegans would form gap junctions exclusively between themselves, and that these new connections could be used to modify existing connections in intact animals. We demonstrate that a genetically modified mammalian connexin gene can be functionally expressed in the C. elegans nervous system. Using this approach, we have been able to target the insertion of functional electrical synapses into existing inhibitory and excitatory chemical synaptic connections in the C. elegans olfactory circuit. We present data demonstrating their impact on neural transmission as well as whole animal behavior.
Daria Solovyeva graduated from the Moscow State Academy of Veterinary Medicine and Biotechnology with a diploma of a biochemist in June 2011. After graduation Solovyeva received a 2-month fellowship from the Max-Plank Society to train at the Max-Planck-Institute for Biophysical Chemistry (Bionanophotonic Department), Göttingen, Germany, where she developed thin and ultrathin films of lipids, proteins, crown-ethers, etc. She then entered the Chemistry Department of the Moscow State Academy of Veterinary Medicine and Biotechnology, where she is currently a Ph.D. student.
In October 2012 Solovyeva received a grant for participation in the 9th Horizons of Molecular Biology symposium (Germany) and was invited to give a talk. Since November 2011 Solovyeva is also a junior research assistant in the Laboratory of Nano-Bioengeneering (National Research Nuclear University). Her current research deals with proteins and hybrid structures with inorganic nanoparticles and is aimed at creating bioinspired photovoltaic devices.
Engineering of photovoltaic cells based on the purple membranes (PMs) of the bacterium Halobacterium salinarum, containing photosensitive membrane protein bacteriorhodopsin (bR) is a challenging bioinspired nanotechnological goal. bR is an integral PM protein capable of transferring the physical energy of solar radiation into the chemical or mechanical energy. PMs possess unique physical, chemical, and dynamic stabilities, which guarantee stable and efficient biological functioning of bR and determines industrial applications of PMs. Here, we report on the development of photovoltaic cells based on oriented PM films, preparation of hybrid nano-biomaterial through controlled integration of semiconductor quantum dots (QDs) into PMs, and engineering of an advanced solar cell on the QD–PM hybrid material. This system has demonstrated enhanced solar energy harvesting and energy transfer, and improved photovoltaic properties due to the integration of QDs absorbing UV-solar solar light several orders of magnitude better than native bR. Moreover, Frster resonance energy transfer (FRET) from QDs to bR with an efficiency approaching 100% may be achieved via careful optical and chemical QD–PM coupling. In addition, the surface charge and functionality of QDs were varied to achieve the best QD integration. As a result, the solar photovoltaic cells based on dried oriented PMs (with and without QDs) were engineered, their properties were analyzed by absorption spectroscopy and laser picosecond fluorescent spectroscopy, and their current–voltage characteristics were measured. The results demonstrate a more than 10-fold increase in the rate of formation of the M412 intermediate in the bR photocycle for the PM–QD system compared with the system employing PMs alone. Thus, we have not only developed a bioinspired nano-biohybrid cell with advanced photovoltaic properties, but also demonstrated the possibility to control the biological function of a photosensitive protein’s by means of FRET from functional semiconductor nanocrystals.
Pasquale Stano completed his graduation in organic chemistry specialized in reaction mechanisms at the University of Pisa, Italy. He moved in Switzerland to join the Luisi group at the Materials Department of ETH Zurich, where he started to work with carnitine-based lipid vesicles for a drug delivery project, with a fellowship granted by the Sigma-Tau pharmaceutical company. In 2003 he moved to Rome, at the Biology Department of Roma3 University, working on the self-reproduction of lipid vesicles intended as primitive cell models. From 2006 to 2008 he was a Junior Fellow of the ‘Enrico Fermi’ research center, dealing with the ‘minimal life’ project.
Currently he is involved, as research fellow at Roma3 University, in the construction of ‘semi-synthetic minimal cells’ (see EU-FP6 Synthcells project). Author of about 50 publications, he is interested in synthetic biology, origin of life, artificial life and artificial intelligence, bio-chem-ICTs, systems chemistry.
In recent years, we have proposed the concept of semi-synthetic minimal cells (SSMCs) (1,2). These are cell-like compartments, based on lipid vesicles (liposomes), filled with the minimal number of biochemical species in order to display living-like properties, like self-maintenance and self-reproduction. Born within the origin-of-life research, SSMCs are now an important pillar of synthetic biology. The SSMCs technology aims at constructing simple cell-like systems from molecular components, by a bottom-up approach, which complements the more traditional top-down one, typical of synthetic biology. The state-of-the-art of SSMCs research focuses on the production of proteins within such synthetic systems, but the ability of assembling compartmentalized systems is rapidly growing, and paves the way to interesting biotechnological applications. In this contribution, we will shortly introduce the concept of SSMCs, and summarize the most relevant results in the field, emphasizing both the scientific and the technological aspects. In addition, we will discuss in detail our recent investigation (3,4) on the remarkable and spontaneous self-organization of solutes and lipids to form a functional synthetic cell. This intriguing observation might be at the basis of the emergence of life on Earth and moreover can be further exploited to advance the technology of SSMCs. (1) Luisi et al. (2006). Approaches to semi-synthetic minimal cells: A review. Naturwissenschaften 93, 1-13. (2) Stano et al. (2011). Compartmentalized reactions as a case of soft-matter biotechnology: Synthesis of proteins and nucleic acids inside lipid vesicles. J. Mat. Chem., 21, 18887-18902 (3) Luisi et al. (2010). Spontaneous protein crowding in liposomes: A new vista for the origin of cellular metabolism. ChemBioChem, 11, 1989-1992. (4) Souza et al. (2011). Spontaneous crowding of ribosomes and proteins inside vesicles: A possible mechanism for the origin of cell metabolism. ChemBioChem, 12, 2325-2330.
Dirk Stemerding is working as a senior researcher Technology Assessment at the Dutch Rathenau Instituut. He participated in the European project Synthetic Biology for Human Health: Ethical and Legal Issues (SYBHEL 2009-2012) in which he was responsible for the work package on public policy. He also contributed to the STOA project Making Perfect Life: bio-engineering in the 21st century (2009-2012).
He is currently leading a work package on synthetic biology in the European project Global Ethics in Science & Technology (GEST 2011-2014) and is involved in a Future Panel project on public health genomics which is part of the European project Parliaments and Civil Society in Technology Assessment (PACITA 2011-2015). In the next four years he will be involved as work package leader in a European Mobilisation and Mutual Learning Action Plan on synthetic biology.
First Author: Dr. Conor M.W. Douglas
Other Author: Dirk Stemerding
SynBio practices are being positioned to address major global health issues through advanced vaccine development, diagnostics, drug synthesis, and the detection and remediation of environmental toxins. Such research is –and stands to be- growing in many parts of the globe, and to include ‘smaller players’ (i.e. iGEM, DIY-Bio), in part due to the particular features of standardization, abstraction, and modular open source parts. To be sure, SynBio is a global endeavour, it has potential for global health, but it will also require global governance. Our understanding of ‘governance’ is not unduly focussed on risks and other potentially negative implications. Instead we understand governance to be the set of institutions and practices involved in the inclusive steering of science and technology towards socially desirable outcomes. This paper reports on original social science research undertaken in project ‘Synthetic Biology for Human Health – Ethical and Legal Issues’ as a part of EU’s FP7 Science and Society program (www.sybhel.org). We report on a workshop we organized for global health experts, SynBio researchers, policy makers and others to identify the positives and productive policy and governance steps that would be needed to foster SynBio addressing major global health issues. Our work outlines the relationship between patent systems, institutional infrastructures, and global health improvements, and discuss some alternative incentive mechanisms for SynBio innovation in global health. We then shift to re-examine what positive and productive governance could mean for SynBio and global health by exploring the role of DIY-Bio and amateur communities, and how opening the research and development discourse in SynBio to various kinds of end-users could facilitate the global uptake and success of its products. Our conclusion suggests roles policy actors could play in fostering positive and productive governance, and the effects what a SynBio roadmap for global health could have in this regard.
Danielle Tullman-Ercek is an assistant professor in the Department of Chemical and Biomolecular Engineering at the University of California Berkeley. Danielle received her B.S. in Chemical Engineering at Illinois Institute of Technology in Chicago, and her Ph.D. in Chemical Engineering from the University of Texas at Austin. She carried out her postdoctoral research at UCSF and the Joint Bioenergy Institute prior to joining Cal in 2009.
Her research focuses on building protein-based devices for applications in bioenergy and drug delivery. She is particularly interested in engineering multi-protein complexes, such as the machines that transport proteins and small molecules across cellular membranes. She is a member of the Berkeley Synthetic Biology Institute, the Synthetic Biology Engineering Research Center, and the Energy Biosciences Institute, and was recently awarded an NSF CAREER award for her work on the construction of bacterial organelles using protein membranes.
The use of microbes to convert biomass to fuel is a promising technology, but the fuels are often toxic to genetically tractable microbial hosts, such as Escherichia coli, at industrially relevant levels. One promising solution to this challenge is to evolve multidrug resistance efflux pumps to secrete fuels from the cell, enabling increased fuel titers in addition to microbial tolerance. To that end, we have used directed evolution to engineer bacterial efflux pumps for enhanced tolerance to butanol. Using multiple rounds of directed evolution involving a selective growth competition method, we have isolated variants of the Escherichia coli AcrB efflux pump that enhance the growth of E. coli in the presence of n-butanol by approximately 25%. The growth enhancement is maintained even as the concentration of inhibitor is increased. Each variant is comprised of several mutations, and we have identified the single amino acid changes in AcrB that are responsible for the enhanced growth phenotype. Furthermore, expression of the variant pumps confers enhanced tolerance to isobutanol and straight-chain alcohols up to n-heptanol, but not chloramphenicol or geraniol. Significantly, we have also found that overexpressing these pumps in butanol production strains leads to increased titers of butanol.
Ilse Wiame obtained an MSc in engineering in biotechnology from the University of Leuven in 1997. She has gained experience in academia and industry before joining the European Patent Office in 2003 as a patent examiner in the field of biotechnology.
In order to properly examine a patent application, the patent office first needs to determine the state of the art for the claimed invention. This is done through a search in collections of documents and databases of patent and non-patent literature. The huge collection of worldwide patent documents is systematically accessible by means of classification symbols. These classification symbols are assigned by the patent office to published patent applications and to patents and they are publicly available and searchable. The European Patent office (EPO) and the United States Patent and Trademark Office (USPTO) have together developed the Cooperative Patent Classification (CPC) system, which was launched on 1 January 2013 and which has the capacity to become the future international standard in patent classification. Classification relevant to the field of synthetic biology includes classification of proteins according to origin or function, classification of fusion proteins according to the function of their subunits and classification of expression systems according to their host cell. Patent classification can be used by the synthetic biology community to search the wealth of information present in patent databases. It also serves as an example of how a database of biological parts can be organized.
Peng Yin is an Assistant Professor of Systems Biology at Harvard Medical School and a Core Faculty Member at Wyss Institute for Biologically Inspired Engineering at Harvard University. His research interests lie at the interface of information science, molecular engineering, and biology. He directs the Molecular Systems Lab at Harvard to engineer programmable molecular systems inspired by biology.
The current focus is to engineer information directed self-assembly of nucleic acid (DNA/RNA) structures and devices, and to exploit such systems to perform useful functions in vitro and in vivo. The lab is developing these structures as templates for fabricating inorganic materials with precisely prescribed shapes and compositions, as imaging probes with programmable geometry and dynamics for multiplexed and quantitative super-resolution imaging, and as programmable scaffolds and circuits to probe and regulate the spatial and temporal behavior of biological processes in living cells. See the lab’s work at http://molsys.net.
I will discuss my lab’s research on engineering synthetic, nucleic acid-based nanostructures and applications in vitro and in vivo. We have recently invented a general framework for programming the self-assembly of short synthetic nucleic acid strands into prescribed target shapes or demonstrating their prescribed dynamic behavior. Using short DNA strands, we have demonstrated the modular construction of sophisticated 2D (Nature, 485:623-626, 2012) and 3D (Science, 338:1177-1183, 2012) structures on the 100-nanometer scale with nanometer precision. Using reconfigurable DNA hairpins, we have demonstrated diverse, dynamic behavior such as catalytic circuits, triggered assembly, and autonomous locomotion (Nature, 451:318, 2008). By interfacing these synthetic, nucleic acid nanostructures with functional molecules, we are developing a diverse range of real-world applications. In biosensing, we have constructed robust and specific probes for detecting single-base changes in a single-stranded DNA/RNA target (Nat. Chem. 4:208-214, 2012). In bioimaging, we have engineered geometrically encoded fluorescent barcodes for highly multiplexed single-molecule imaging (Nat. Chem., 4:832-839, 2012). In nanofabrication, we have developed a versatile framework for producing inorganic materials (e.g. graphene [Nat. Communications, 2013, in press], silver, gold) with arbitrary prescribed nanometer scale shapes. We are migrating our capability on the rational engineering of DNA structures in test tubes to RNA structures in living cells. I will discuss our ongoing work on developing RNA based scaffolds, conditional regulators, and computational modules to probe and program biology.