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overview My lab studies the mechanisms by which protein functions evolve. We do this by phylogenetically reconstructing the histories of ancient proteins and then synthesizing, manipulating, and experimentally characterizing their biological functions and physical properties. This kind of work is powerful and fun — and possible at all — because we are a diverse group of evolutionary biologists, biochemists, biophysicists, computational biologists, geneticists, and molecular biologists, all working together and freely mingling our expertise, techniques, and ideas. We address classical and recent questions about the nature of evolutionary processes, such as: How do complex molecular systems evolve? Does evolution proceed by a few large-effect or many small-effect mutations? Does epistasis shape the evolutionary process and make the pathways and outcomes of evolution contingent on chance events? Is evolution reversible? How does the architecture of biological systems shape the evolutionary process? How did evolution produce those architectures in the first place? Evolutionary analysis can also help address core questions in biochemistry, biophysics, and molecular biology. Why do proteins have the particular architectures that they do? How does that architecture itself evolve? What structural and genetic mechanisms cause functions to differ between members of protein families? How do molecular machines, allostery, and molecular interfaces evolve? Are proteins’ physical properties always optimized for their functions, and if not, why not? Can history explain why particular proteins are subject to interference by particular drugs and pollutants? We have found that detailed reconstruction of proteins’ histories helps us to understand why and how their present-day descendants work as they do today.
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  • Biophysics