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NSF funds new synthetic-biology center at Berkeley
Potential to revolutionize the biotech industry and, ultimately, solve the world's most intractable problems

| 30 August 2006

A new campus research center launched this summer will seek to make it as quick and easy to engineer biology as it now is to assemble microprocessors, hard drives, and memory chips into a computer.

The center will focus on an emerging discipline - synthetic biology - that researchers say will transform the biotechnology, high-tech, pharmaceutical, and chemical industries by providing less expensive drugs and fuels, novel materials, biological sensors, and replacement organs from stem cells.

Funded by a five-year, $16 million grant from the National Science Foundation (NSF), the Synthetic Biology Engineering Research Center (SynBERC) is gathering pioneers in the field of synthetic biology from around the United States into a unique "engineering" center. The center's researchers hope to ignite the field of synthetic biology in the same way that the developers of standardized integrated circuits in the 1960s ignited the field of semiconductor electronics. Matching funds from industry and the participating universities bring the total five-year commitment to $20 million, with the NSF offering the possibility of a five-year extension of the grant.

Synthetic biology is the design and construction of new biological entities such as enzymes, genetic circuits, and cells, or the redesign of existing biological systems. The field builds upon advances in molecular, cell, and systems biology and seeks to transform biology.

The element that distinguishes synthetic biology from traditional molecular and cellular biology is the focus on the design and construction of core components that can be modeled, understood, and tuned to meet specific performance criteria, and the assembly of these smaller parts and devices into larger integrated systems that solve specific problems.

"The focus of SynBERC is to make biology easier to engineer," says SynBERC director Jay Keasling, professor of chemical engineering and bioengineering. "SynBERC will construct the biological components that will allow engineers to build biological solutions to important societal problems, such as the environmentally friendly production of chemicals using microbes, or replacing damaged or malfunctioning genetic circuits inside human cells to cure disease."

Center collaborators hail from the Massachusetts Institute of Technology (MIT), Harvard University, UC San Francisco, and Prairie View A&M University in Texas.

Stimulating new multidisciplinary fields is one of the prime objectives of the California Institute for Quantitative Biomedical Research (QB3), which spearheaded the center. QB3 involves researchers at Berkeley, UCSF, and UC Santa Cruz, along with industry partners. At Berkeley, QB3 has made synthetic biology one of its key initiatives, so SynBERC funding is a major milestone.

"QB3 is stimulating science at the boundaries between traditional disciplines, where many of the most exciting discoveries take place," said Chancellor Robert Birgeneau. "At Berkeley, QB3's success in bringing the nation's leading synthetic biologists together and garnering industry support for SynBERC demonstrates the institute's enormous potential to foster innovative science and spawn new industries that may change the landscape in the business world."

Keasling compares the field of synthetic biology today to the field of electronics before standardized parts allowed engineers to mix and match components to produce an infinite variety of devices. Today, for example, synthetic biologists must assemble a unique suite of genes for each experiment and find a way to insert them into microbes to force them to synthesize a specific compound.

"You can swap hard drives in and out of your computer because there are standard connections. You don't have to worry about what goes on inside that box," he said. "We don't yet have the ability in biology to swap parts in and out of a microbe without worrying about the connections or whether the parts will work."

SynBERC will concentrate on developing these interchangeable parts and, in the process, demonstrating that standardization of the field will reap huge payoffs. For example, its researchers hope to engineer microbes to produce the anti-cancer drugs vincristine and vinblastine - currently used to treat lymphoma, leukemia, and some types of breast and lung cancer - that today are extracted from plants and, because of their chemical complexity, are a challenge to synthesize in the laboratory. Kristala Jones Prather, assistant professor of chemical engineering at MIT, will lead this effort.

Another proof of concept - a so-called testbed - will be a microbe that invades and destroys a tumor. Chris Voigt, an assistant professor of pharmaceutical chemistry at UCSF, will head up that project.

Pondering the best approach

One of the key questions is how best to develop a "chassis" into which genetic parts can be implanted, just like the chassis or frame of a car is used to build different models. According to Drew Endy, an assistant professor of biological engineering at MIT, it may be best to take a complicated cell and simplify it by stripping out many of the genes not necessary for life, leaving basically a power supply for whatever genes are implanted.

Alternatively, one could build an entirely new system within a compartment of the cell - an organelle, or specialized cellular part, like the mitochondria of an animal cell or the photosynthesizing chloroplast of a plant cell.

"We have no idea what approach is going to work best," Endy said, noting that while he pursues the latter approach, his MIT colleague Tom Knight, a senior research scientist, plans to pursue the former. "This grant gives us the chance to explore both techniques and find out."

SynBERC engineers will make the designs for their biological parts and devices available to other engineers through an open-source registry of standard biological parts. This will allow other biological engineers to re-use parts and devices developed for one application in other, very different applications, much like microprocessors are now used in computers, cell phones, and automobiles.

And while SynBERC scientists at UCSF and MIT engineer biological parts that can be assembled inside a chassis to accomplish a particular goal, researchers at Harvard will concentrate on both parts and chassis. "The role of our group is developing technology for large genome constructs and safer cellular chassis," says team member George Church, a Harvard professor of genetics.

Keasling expects that the techniques, chassis, parts, and devices developed will help his other efforts at Berkeley: to develop a microbe that changes the hard-to-digest cellulose of plants directly into fuel, and to improve the bacteria and yeast he has already engineered to produce an antimalarial drug, artemisinin.

Industry will be among those benefiting from this work, which is why industry participation and investment is a major goal of the center. Twelve firms have committed to membership, including suppliers of genetic tools and custom DNA synthesis, pharmaceutical and chemical companies, and businesses interested in developing simulation software for the field of synthetic biology.

These companies will advise SynBERC researchers on future research directions, technology transfer, and industrial practice, in return getting access to research interns, postdocs, and, ultimately, newly minted graduates trained at the cutting edge of synthetic biology.

The NSF grant also will allow examination of the societal, ethical, and biosecurity or biosafety implications of synthetic biology in a way that integrates ethics and risk into the design process.

"We are going to make biology easier to engineer, which means it will be easier for someone to misuse the technology," Keasling said. "To minimize its misuse, we will bring together social scientists, such as ethicists, economists, and public- policy experts, with synthetic biologists to think through the societal implications of synthetic biology. Our goal is to maximize the use and positive impact of synthetic biology to solve the world's most significant problems."