Research Experiences for Undergraduates

Building on advances in genome engineering technologies, researchers at the NSF-funded Synthetic Biology Engineering Research Center (SynBERC), headquartered at the University of California, Berkeley, have begun to develop MAGE (Multiplex Automated Genome Engineering), a high-throughput platform for construction of cellular chasses. MAGE allows for simultaneous creation of a variety of chasses in one reaction chamber in an automated and combinatorial fashion. The platform is a fully automated, modular device containing a growth chamber and attachment/modules to perform electroporation or other methods for delivering DNA into cell cultures to produce specialized bacteria, drugs, chemicals, etc.

During operation, the device is run continuously and cyclically through a series of steps, including: growth of cell cultures to a preset density; induction of cellular recombination machinery or introduction of inducer molecules; washing of the cultures through rounds of filtration and re-suspension; addition and delivery of DNA material; and re-suspension of the electroporated cells with growth media. Any number of DNA materials can be delivered into the cells, including synthetic oligonucleotides, polymerase chain reaction (PCR) products, plasmids, and phage. For the purpose of creating cellular chasses, pools of different oligonucleotides that target different loci in the E. coli chromosome are continuously and cyclically introduced into the cells to promote rapid, site-specific changes to these locations in a large set of genomes. The desired chassis or set of chasses are then isolated through a simple selection or screen. The integrated componentry of the MAGE device represents a scalable, cost-efficient, and high-throughput solution for rapid multiplex genome engineering.

Primary Strategic Outcome Goal:
Engineering Research Centers

Secondary Strategic Outcome Goals:
In terms of intellectual merit, why is this outcome notable and/or important?
Synthetic biology is a new field that is advancing rapidly, and this ERC is developing an array of novel tools for genetic engineering. The development described here is a cost-efficient, high-throughput system for automating the engineering of genomes.

In terms of broader impacts , why is this outcome notable and/or important?
Merit Review Broader Impacts Criterion: Representative Activities, July 2007
Every Engineering Research Center involves the participation of several institutions across the U.S., as well as a diverse faculty and student body. Both undergraduate and graduate students are involved in the research. The new technology will be disseminated broadly throughout the synthetic biology research community to accelerate progress in this field, which offers potential benefits in medicine, agriculture, homeland security, environmental protection, and many other fields.

Does this highlight represent transformative or potentially transformative research? If so, please explain why. For more information, see Report to  Congress: Transformative Research at the National Science Foundation, April 16, 2008
Yes
Automating the engineering of genomes through synthetic biology will move genetic engineering to a new level of possibility.

Does this highlight represent Broadening Participation? If so, please explain why.
For more information, see Broadening Participation at the National Science Foundation: A Framework for Action
Yes
Every Engineering Research Center involves the participation of several institutions across the U.S., as well as a diverse faculty and student body.

Are there existing or potential societal benefits of this research? It is important for NSF to be able to provide examples of NSF-supported research that have societal benefits, including benefits to the U.S. economy.
For more information, see Excerpt from Merit Review Broader Impacts Criterion: Representative Activities, July 2007
Yes
Advances in genetic engineering such as this technology offer potential benefits in medicine, agriculture, homeland security, environmental protection, andmany other fields.

ENG/EEC 2009