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MIT model could predict cells' response to drugs

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One of the key questions that Lauffenburger's group tackled was understanding the way in which cells interpret the signals they receive and how they arrive at the correct result.

The researchers approached the problem quantitatively, measuring activity levels in five major signaling pathways after colon epithelial cells were exposed to a variety of environmental stimuli. The behavioral outcome-cell death, inflammatory cytokine production, etc., was also measured.

Using that data, they constructed a model correlating outcomes with the combined levels of activity in the multiple pathways. The model was then used to correctly predict what would happen to two other types of epithelial cells when exposed to the same stimuli.

"Cells appear to be adding up information across multiple pathways in a common manner, even though the outcome of the calculations is different because the pathway activities are different," said Lauffenburger.

The researchers also tested the model on a type of blood cell, but in this case, it failed to accurately predict behavioral outcomes. The fact that a model developed with colon epithelial cells only worked for other types of epithelial cells is not surprising because different tissue types process information in different ways, Lauffenburger said.

To develop safe and effective drugs, researchers need to be able to understand how a drug works in the context of a network governing cell functions, not just its effect on an individual molecule. Lauffenburger envisions that drug companies could use this kind of model to test the effects of drugs that inhibit some step in a particular pathway.


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Contact: Patti Richards
prichards@mit.edu
617-253-8923
Massachusetts Institute of Technology
30-Jul-2007


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