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Computer modeling reveals hidden conversations within cells

ters in the model. As they were developing the model, they repeatedly tested and refined it by comparing the model's predictions with the results of experiments with living cells.

"The beauty of this kind of interdisciplinary work is the almost circular way the model's predictions drive the design of new experiments, and the how results of those experiments can be fed back into the model to improve it," said Shannon Werner, a graduate student in chemistry and biochemistry, who did the experimental work described in the paper.

Once the model consistently predicted the behavior of living cells in a variety of experimental conditions, the researchers used the model to infer what was going on inside cells in much greater detail than would be possible through laboratory experiments alone.

The model revealed why two natural chemicals have opposite physiological effects. When exposed to one of the chemicals, the proteins create positive feedback that lengthens the amount of time they are active. When exposed to the other chemical, they initiate negative feedback, which shuts them down rapidly.

"The prevailing view has been that proteins are either on or off like a light switch, but that didn't explain how activating the same proteins with different chemicals could have opposing effects on cells," explained Hoffmann. "Our model shows that, analogous to how a telephone transmits an infinite number of different signals along a single wire, it is the timing of the proteins' activity that allows them to exert intricate control over the behavior of a cell. The computer model reveals the hidden conversations in the cell's wiring."

The researchers attribute their success in developing the computer model, despite criticism that the computational approach would require too many simplifications to accurately model cell communication, to the diverse expertise they brought together.

"Developing a computer model is both science a
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Contact: Sherry Seethaler
sseethaler@ucsd.edu
858-534-4656
University of California - San Diego
15-Sep-2005


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