It has taken more than 50 years to accumulate the current body of knowledge on Escherichia coli, a bacterium which is one of the best studied organisms in biology. Now, bioengineers at the University of California San Diego have integrated this knowledge into the first genome-scale model of the gene regulatory system in E.coli. The computational model helps to define the rules governing cell function and quickly enabled an exponential increase in the understanding of the regulatory system in E. coli. Their work, which is published in the May 6, 2004 issue of Nature, represents a new way to systematically drive biological discovery.

"This research is evidence of how much more quickly biological discovery is going to progress now, given that we have high-throughput experimental tools for gathering large volumes of data, and the use of these tools can be guided by computer models," said Bernhard Palsson, professor of bioengineering at the UCSD Jacobs School of Engineering. Palsson co-authored the study with his UCSD bioengineering student Markus Covert, who is now a post-doctoral researcher at the California Institute of Technology.

"We have demonstrated that we can reverse-engineer a cellular regulatory system at the genome scale, and then use that model to systematically gain new knowledge about how the cell functions," said Palsson.

In 2000, Palsson completed an in silico (computational) model of E. coli metabolism that is now being used by scientists worldwide to design and interpret laboratory experiments as well as engineer strains for industrial purposes. In this more recent work, Covert modeled the regulatory network in E. coli representing how the cell responds to environmental cues and expresses genes involved in cellular metabolism. He scoured the scientific literature to reconstruct an E. coli model incorporating all known data about regulatory network components, their functions and their actions.

The UCSD model now includes
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Contact: Denine Hagen
dhagen@ucsd.edu
858-534-2920
University of California - San Diego
5-May-2004

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