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Many bodies prompt stem cells to change
Date:6/16/2014

i of Nagoya University but now takes into account the fact that not one but many genes can be responsible for even a single decision in a cellular process.

"This is what Bin figured out, that one could generalize our 2003 model to be much more realistic about how several different proteins bind to DNA in order to turn it on or off," Wolynes said.

A rigorous theoretical approach to determine the transition pathways and rates between steady states was also important, Zhang said. "This is crucial for understanding the mechanism of how stem cell differentiation occurs," he said.

Wolynes said that because the stem cell is stochastic -- that is, its fate is not pre-determined -- "we had to ask why a gene doesn't constantly flip randomly from one state to another state. This paper for the first time describes how we can, for a pretty complicated circuit, figure out there are only certain periods during which the flipping can occur, following a well-defined transition pathway."

In previous models of gene networks, "Instead of focusing on proteins actually binding to DNA, they just say, 'Well, there's a certain high level of this protein or low level of that protein,'" Wolynes said. "At first, that sounds easier to study because you can measure how much protein you've got. But you don't always know if it is bound. It has become increasingly clear that the rate of protein binding to DNA plays an important role in gene expression, particularly in eukaryotic systems."

The notion that many-body effects even existed in cells began in 1942 when British scientist C.H. Waddington established the idea of an epigenetic landscape for stem cells as a way to describe why pluripotent cells in embryos are destined to turn into bone, muscle and all the other parts of the body but don't turn back. Waddington compared the cells' paths to marbles rolling to the bottom of a valley.

That concept rang true to Wolynes. His energy landscape
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Contact: David Ruth
david@rice.edu
713-348-6327
Rice University
Source:Eurekalert  

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