"His analogy the idea of falling down through a valley kicked around for a long time, but it was hard to make it mathematically precise. In his time, they didn't know about DNA," Wolynes said.
In both energy and epigenetic landscapes, Wolynes said, the steady state at the bottom is an attractor. "It means wherever you start from, you end up attracted to that same place," he said. "In genetic networks, things like steadily oscillating patterns can also be considered attractors."
Once biologists began to understand genetic switches in DNA, the whole picture became more complicated, he said. "The landscape now has to incorporate the active parts of DNA that are trying to decide whether to turn this gene on or that gene off. In the '50s, we learned how genes made decisions on the basis of their production of proteins. These proteins then act back on the same genes in a kind of feedback loop."
The loops allow genes to remain active for far longer than it would take a protein simply to bind or unbind to a section of DNA. In the researchers' equations, the loops become attractors that help regulate transformation of the cell and can be mapped onto the many-body landscape.
Analyzing the coupled dynamics of all these chemical reactions in a cell could be done by brute force, he said, but the computational cost would be enormous. So the Rice team decided to take a big-picture approach based on Wolynes' earlier work. It so happened that the resulting theoretical models of embryonic stem cells matched nicely with what experimentalists had seen in their s
|Contact: David Ruth|