JBEI Berkeley Develops Master Controls for Synthetic Biology

Synthetic biology is an emerging scientific field in which novel biological devices, such as molecules, genetic circuits or cells, are designed and constructed, or existing biological systems, such as microbes, are re-designed and engineered. A major goal is to produce valuable chemical products from simple, inexpensive and renewable starting materials in a sustainable manner. As with other engineering disciplines, CAD tools for simulating and designing global functions based upon local component behaviors are essential for constructing complex biological devices and systems. However, until this work, CAD-type models and simulation tools for biology have been very limited...

...“Because biological systems exhibit functional complexity at multiple scales, a big question has been whether effective design tools can be created to increase the sizes and complexities of the microbial systems we engineer to meet specific needs,” says Jay Keasling, director of JBEI and a world authority on synthetic biology and metabolic engineering. “Our work establishes a foundation for developing CAD platforms to engineer complex RNA-based control systems that can process cellular information and program the expression of very large numbers of genes. Perhaps even more importantly, we have provided a framework for studying RNA functions and demonstrated the potential of using biochemical and biophysical modeling to develop rigorous design-driven engineering strategies for biology.”

Keasling, who also holds appointments with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkley, is the corresponding author of a paper in the journal Science that describes this work. The paper is titled “Model-driven engineering of RNA devices to quantitatively-program gene expression.” Other co-authors are James Carothers, Jonathan Goler and Darmawi Juminaga. _LawrenceBerkeleyLab_via_GCC

The art of dealing with complexity will separate those societies which succeed from those which fail. Some levels of complexity cannot be totally mastered, yet they can be "accomodated" or dealt with.

Learning to fine-program biological organisms to produce substances of use to humans in useful form and quantity, would allow a passage through a threshold separating one type of society from earlier types. This has always been the promise of synthetic biology, but the specific tools to be used have been either lacking, or far too crude. This is changing.

“We needed to formulate models that would be sophisticated enough to capture the details required for simulating system functions, but simple enough to be framed in terms of measurable and tunable component characteristics or design variables,” Carothers says. “We think of design variables as the parts of the system that can be predictably modified, in the same way that a chemical engineer might tune the operation of a chemical plant by turning knobs that control fluid flow through valves. In our case, knob-turns are represented by specific kinetic terms for RNA folding and ribozyme catalysis, and our models are needed to tell us how a combination of these knob-turns will affect overall system function.”

JBEI researchers are now using their RNA CAD-type models and simulations as well as the ribozyme and aptazyme devices they constructed to help them engineer metabolic pathways that will increase microbial fuel production. JBEI is one of three DOE Bioenergy Research Centers established by DOE’s Office of Science to advance the technology for the commercial production of clean, green and renewable biofuels. A key to JBEI’s success will be the engineering of microbes that can digest lignocellulosic biomass and synthesize from the sugars transportation fuels that can replace gasoline, diesel and jet fuels in today’s engines.

“In addition to advanced biofuels, we’re also looking into engineering microbes to produce chemicals from renewable feedstocks that are difficult to produce cheaply and in high yield using traditional organic chemistry technology,” Carothers says. _LBL

Brian Wang provides additional information and materials

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