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Cellular pathway includes a 'clock' that steers gene activity

es through a cell pathway to genes in the nucleus, it prompts the genes to send out their own instructions, directing the cell to assemble proteins to carry out various tasks. By developing a better understanding of the way information travels along a pathway, Levchenko said, researchers may be able to create drugs that disrupt or change this line of communication, and in turn affect overall functioning within the cell. For example, a drug designed to shut down the NF-kappaB pathway might cause a cancer cell to commit suicide through a biological process called apoptosis. "We know that cancer cells use this pathway," he said. "If we can find a smart way to cut this 'wire,' it will be much easier to kill the cancer cells."

Levchenko and his colleagues made their discovery by first developing a computer model showing how they believed the pathway operates. Then they verified their results by studying live cells in the lab. Finally, they used the validated model to guide further experiments. Although mouse cells called fibroblasts were used, Levchenko said the findings should also hold true for human fibroblasts and other cell types.

Because the computer model has been validated, it could be used to speed up the development of pharmaceuticals that might affect the cell pathway, said Levchenko, who is a part of a computational biology research team based at the Whitaker Biomedical Engineering Institute at Johns Hopkins. He said drug developers could use the computer model to quickly test how various compounds may affect the cell behavior before launching more time-consuming lab tests with live cells. "This has given us a very good tool to predict things that may happen when the pathway properties are altered, reducing the need to engage in exhaustive animal tests," Levchenko said.


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Contact: Phil Sneiderman
prs@jhu.edu
410-516-7907
Johns Hopkins University
7-Nov-2002


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