SBI Research Themes
Scientists and engineers at the Synthetic Biology Institute are engaged in both foundational and applications research the following focus areas:
SBI aims to realize the huge potential of synthetic biology in the production of medicines and diagnostic compounds. Research is advancing the development both of established classes of therapeutics — small molecules, proteins, and vaccines — and of potential new classes based on engineered cells, microbes, viruses, or non-living agents with complex biological compositions. These latter agents could have broad applications for medical problems that are not easily solved with similar drugs; they may find use as anti-cancer agents, gene therapies, stem-cell therapies, probiotics, and live vaccines. (The foundational research for many of these new applications is being conducted by the Biohybrid Systems Design focus group at SBI.) Current projects in this SBI research area include developing bacterial and immune-cell-based immunotherapies and vaccines, engineering viral gene therapy systems for safe and effective delivery of genes to particular target tissues, and coaxing stem cells into programmed tissues.
Chemicals, Fuels & Materials
Chemicals: A vast number of naturally occurring biological systems can convert simple substrates into the products that cells need for growth and survival. Synthetic biology could harness this biotransformation potential to produce many other chemicals that address unmet clinical and industrial needs. At SBI, researchers are developing new computational tools and methods for high-throughput system assembly and analysis to enable the production of drugs, bulk chemicals, and fuels in microbial hosts. Recent improvements in synthetic biology techniques already have yielded successes, and SBI initiatives will build on these advances, including work toward better macromolecular engineering tools, high-throughput screening of biomolecular activities, and better modular and predictable control of central cellular processes such as gene expression, protein folding and stability, and secretion.
Bioenergy & Biofuels: The richness and versatility of biological systems make them ideally suited to solve some of the world’s must pressing challenges, including the conversion of cheap, renewable resources into energy-rich molecules. The U.S. Department of Energy, for example, has identified at least 120 chemicals as high-value targets for bio-manufacture that can be created from biological feedstocks. SBI is developing the infrastructure needed to make bioenergy abundant, affordable, and sustainable. Considerable progress has already been made toward engineering microorganisms to produce fuels, but the more advanced tools of synthetic biology will be needed to achieve a true breakthrough in the biologic production of energy. New directions may involve optimization of plants for growth in currently non-arable soils, better enzymes for decomposition, and biodirected light-harvesting materials for direct conversion of sunlight into electricity or fuel. Similar tools are already being created by SBI in its other applications focus areas. These include well-characterized gene-expression components and hosts for chemical synthesis, bioinformatic approaches for the identification of useful enzymes and functions from sequence and functional genomics data, tools for enzyme and pathway design, standards for the connection of these components to make larger functioning devices, computer-aided design software, and debugging tools for biological designs.
Advanced Materials: By understanding and redesigning nature’s building blocks and directing their assembly into complex working structures, SBI is developing new biomaterials that address important human needs. Its research goals include engineering cellular membranes to make them more robust, creating novel trans-membrane uptake and secretion pathways, and advancing nanotechnology by using proteins as templating agents. SBI also aims to engineer biomaterial scaffolds to provide robust platforms for investigating cell physiology and fabricating functional tissues and organs outside the human body. The goal of this work is to create new opportunities for practical application of cells beyond the limits of natural physiology.
Environment & Agriculture
Synthetic biology has many significant potential uses, direct and indirect, in protecting and restoring the environment. It could lead to the development of new genetically engineered microbes to clean water, soil, and air. It could make possible the transformation of oceanic algal ecosystems for carbon sequestration. It might have an even greater, if less direct, benefit through the engineering of crops, both for food and fuel, that can grow in less arable land and require less energy than current crops to produce. By opening up more land to productive use, synthetic biology could help preserve valuable wildlands and ease the conflict between food and fuel production. Working closely with the SBI Bioenergy group, researchers in this area are building on foundational SBI research to develop these and other potential environmental applications for synthetic biology.
Foundational Science & Technology
Synthetic biology requires a strong base of theoretical and practical knowledge covering design, computation, and fabrication to reach its potential to serve human and societal needs. SBI is building this foundation through five research focus areas, ranging from the design of new molecules to the development and refinement of bio-fabrication methods. These five research programs create the tools and techniques that make it possible to engineer new cellular functions efficiently, predictably, and safely.
Macromolecular Design: The design of macromolecules is fundamental to all SBI engineering activities. It can involve repurposing natural molecules in synthetic pathways to create novel activities, or modifying the molecules themselves to provide new chemical properties, stability in new environmental conditions, or entirely new structures and materials. In all cases, the building blocks of cellular function — protein, RNA, DNA, and even large lipids and polysaccharides — provide the foundational materials for synthetic biology applications. This research theme underlies the work of Berkeley researchers who are applying macromolecular engineering in several areas, such as changing the activity of existing enzymes important to the chemical industry; making the engineering of gene expression more homogeneous, predictable and scalable; and creating completely novel macromolecular superstructures.
Participating SBI researchers:
Jennifer A. Doudna
Cheryl A. Kerfeld
Cellular Network Design: SBI researchers are developing approaches for discovering and designing complex biological networks with useful functions. Systems can be found in nature and “repackaged” so that they can be incorporated and operate reliably in engineered systems for chemical synthesis, survival in varied environments, sensing different conditions, and other sophisticated behaviors. Wholly new networks of macromolecules can be designed to create, for example, new types of cell walls in plants optimized for production of biofuels, or new cells that implement therapeutic effects in humans. Such large-scale engineering is made possible by new techniques that allow rapid assembly and implant of synthetic networks, along with whole-genome engineering of cells to improve safety and compatibility with these exogeneous systems. SBI researchers also study how designed networks can maintain reliable function and be contained in varying environments. Scientists and engineers in this area are developing a systems-level understanding of biological function and design, drawing from the fields of comparative functional genomics, systems biology, and macromolecular design. SBI is developing foundational theory and the computational and experimental technologies to advance applications in health, the environment, and bioenergy.
Participating SBI researchers:
Dan Fletcher, Theme Leader
Cheryl A. Kerfeld
Biohybrid Systems Design: Biohybrid devices may offer the better of two worlds, particularly in medicine. They combine the targeted functionality of biological molecules with the safety of non-biologic delivery systems. For example, a protein, microbe or virus could be engineered to attack a specific type of tumor, and it could be encased in a chemical compartment that both detects the presence of the targeted tumor and prevents unwanted interaction between the biological element and its surroundings. SBI is working to develop the components of such systems and the methods to produce them on an industrial scale. Researchers view the biohybrid option as a means to avoid the difficulties of a purely synthetic approach to biomimetic, adaptive design, as well as to avert the hazards of purely biologic approaches, such as viral and bacterial therapies for cancer. The methods for using biology to drive assembly of non-biological systems have been improving, but they remain an art; in addition, the tools have yet to be created for scaling manufacture and enabling better computational design of biohybrid systems. SBI is focused on bridging these gaps to new technology that could produce huge benefits in human health.
BioCAD: Developing a suite of computational tools for synthetic biology is a key multidisciplinary effort of SBI. Researchers draw on bioinformatics, machine learning, and biophysical and systems biology modeling to solve design and manufacturing problems in synthetic biology. They are working toward building a computational infrastructure to support a biological-design industry, in much the same way as an earlier generation of UC Berkeley engineers developed software that is now the standard for circuit simulation, design, and fabrication for the electronics industry. SBI’s BioCAD work is integrated with its BIOFAB efforts, creating an infrastructure that not only serves the institute but also offers a model for others to emulate in establishing cellular bioengineering/biodesign facilities.
BIOFAB: SBI researchers are pursuing the development of new biofabrication capabilities, working to streamline, refine, and characterize the activity of genetic control elements so that large-scale collections of genetic parts can be utilized as standardized components to assemble engineered biological systems. The goal is to create the world’s first operating production-level biofabrication facility. To advance this goal, the National Science Foundation recently awarded seed money to ramp up BIOFAB (the International Open Facility Advancing Biotechnology), a joint effort between UC Berkeley and Stanford University, working collaboratively with the Synthetic Biology Engineering Research Center (SynBERC), a UC Berkeley-led, NSF-funded endeavor. SBI’s core technical goals in this area are (1) to decouple design and fabrication in genetic engineering, thus enabling assembly of complex function without constantly requiring biophysical measurement and modeling, and (2) to develop libraries of standardized genetic components to shorten the development time and lower the costs of synthetic biology advances for academic and biotech laboratories. SBI is looking to expand this research effort and engage multiple international partners.
Ethical, Economic, Environmental, Legal & Social Aspects (E3LSA)
Synthetic biology has the potential for a vast impact on society — and that makes it a target for controversy. SBI believes that understanding these impacts, their implications, and their remediation is as central to its mission as advancing the engineering and science that underlie the field.
Innovations sparked by synthetic biology could lead to new industries, but also to changes in traditional ones, affecting jobs and communities. Big-picture questions are on the minds of many — including SBI researchers — about the rational engineering of life forms to fight disease, clean up the environment, or produce food crops or plants for bioenergy production. Questions of ethics, safety, and policy are part of SBI’s focus as we create new knowledge about repurposing cells and molecules for technological advances.
SBI’s research agenda includes exploration of the ethical, environmental, economic, legal, and societal aspects of synthetic biology, to provide the emerging synthetic-biology industry with practical guidelines and standards. The institute also embraces its role in educating the public about the science and engineering of synthetic biology, including outreach to K-12 students, our traditional mission of educating undergraduate and graduate students, and programs to inform the broader community.
Participating SBI researchers: