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EGFR: A molecular lab rat let loose in systems biology

SAN FRANCISCO -- Epidermal growth factor and its receptor system, or EGFR, is well-trodden territory in molecular biology. And it's no wonder. This is one critical community of proteins, responsible for everything from the development of insect eyes and the mouse brain to human heart and skin. When EGFR breaks down, cancer and other diseases crop up.

EGFR is the veritable lab rat of molecular systems. Going on five decades now, biologists in labs around the world, not unlike motorheads under the hood with carburetors and plugs, have plucked out and examined every conceivable component of the EGFR network.

Along comes systems biology, shiny-new and bursting with promise, outfitted with high-powered computing and modeling capabilities that are being brought to bear on the fundamental problems of human physiology and disease pathology. And what undiscovered country does H. Steven Wiley and his colleagues at the Pacific Northwest National Laboratory choose to flood with the piercing light of this new science?

Why, naturally, this same receptor network.

"A lot of people ask, 'Why this system? It's the prototypical receptor system. We know everything about it. We know all the parts,' " says Wiley, chief scientist and director of the Biomolecular Systems Initiative at the Department of Energy lab in Richland, Wash.

Wiley's reply: The whole is much more than the sum of its parts -- receptors, ligands, enzymes, substrates -- and a great starting point if you know what each of those parts is.

"We're looking at the whole family of parts that govern cell behavior," Wiley says. "We need to know how they react with each other and other parts of the system."

Wiley likens the known world of the EGFR to a big-city phone book. It's all there, in black and white and yellow, and it tells you next to nothing about the city or how its inhabitants interact.

"The systems approach," Wiley says, "enables us
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Contact: Bill Cannon
cannon@pnl.gov
509-531-7345
DOE/Pacific Northwest National Laboratory
17-Dec-2003


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