Solving Molecular Mysteries of the Cell
Peter Wolynes thinks about big questions and tiny structures in biology, chemistry and physics. His collaborative research at the Center for Theoretical Biological Physics is helping to map the architecture of the human genome. In my lab, I’m trying to understand really funda-
mental things about biology. Our work often opens up more questions than answers. We first have to uncover how individual molecules in biological systems work, then see how they cooperate with each other. The ways that genes are regulated on a biochemical level is still a big question. We know regulation happens, but what’s really going on at the molecular level? Biochemistry has made huge advances on such questions by taking molecules out of cells, finding out what they are and then showing that they’re involved in chemical reactions of various types. But we don’t always know if those molecules behave the same way inside a cell. Does the structure of the cell matter? Does it change anything? We do not know how structures are set up on the cell scale. Protein folding is a great example of something we think we understand on a molecular level. We know for the most part how proteins fold — they’re long, stringy molecules, and certain spots on the molecule are attracted to other specific spots. As a protein shakes around randomly inside a cell, those spots eventually find each other and assemble the molecule in three dimensions in a very predictable way. As you get to bigger structures like the DNA in the genome, though, it’s not clear exactly how the physics works. A chromosome is a much bigger molecule than a protein — so how much of its structure emerges automatically? Is it shaped by random jostling as well? Or is it powered by specific motors that push it into place? The mathematics of how to describe the architecture and machinery of the cell in molecular terms doesn’t exist. However, it affects everything in our bodies.
Peter Wolynes is the D.R. Bullard-Welch Foundation Professor of Science, a professor of chemistry, physics and astronomy, and materials science and nanoengineering. His lab is part of the Center for Theoretical and Biological Physics. 26
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