Presenter(s): Genevieve Dorrell − Biology, Computer Science
Co Presenter(s): Daria Wonderlick
Faculty Mentor(s): Mike Harms, Anneliese Morrison
Poster 11
Research Area: Evolutionary Biophyisics
Proteins evolve new functions by acquiring mutations. Understanding this process is critical to combating antibiotic and pesticide resistance. Studies have shown that the effects of mutations alone versus in combination are not always equal. This is called epistasis, and it impedes our ability to predict protein evolution. Our project aims to understand one biophysical source of epistasis. Previous theoretical work in the Harms lab revealed that epistasis could arise from the existence of multiple conformations of a protein. To probe this, we are manipulating the number of conformations available to the lac repressor protein. We are using drugs that shift the lac repressor into either its DNA-bound or DNA-unbound conformation. We perform a colorimetric assay to quantitatively detect which conformations are favored by lac repressor mutants, and then infer epistasis between mutations on these functional readouts. If we limit the number of conformations a protein can adopt and see a proportional change in epistasis, we will have evidence to support that epistasis arises from this intrinsic biophysical of property of proteins.