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Biochemistry & Molecular Biology
Proteins are macromolecules that must fold correctly to perform their functions in cells. Cells use several quality control systems to ensure proteins fold correctly. For example, chaperones are proteins that help to prevent other proteins from misfolding. Prions are a subset of misfolded proteins that are self-propagating and are infectious, thus transforming correctly folded proteins into their prion counterparts. Yeast are used as model organisms since they share many genes with humans but are easier to manipulate experimentally. Whereas human prions cause diseases, such as Creutzfeldt-Jakob disease, yeast prions sometimes provide benefits to the cell. Previous studies in our lab have shown that when certain chaperones are functioning normally in yeast, prion formation is reduced. Whether the human homologs of these chaperones can similarly suppress prion formation is unknown. To test whether this is the case, I am engineering yeast in which some chaperones have been replaced with their human counterparts, to assess whether the human chaperones inhibit prion formation. I have successfully engineered yeast containing one such chaperone, and soon plan to begin measuring prion formation in this strain. Additionally, to explore whether prions give yeast an advantage growing in various conditions, I performed growth competition experiments in which prion-containing cells competed with their genetically identical prion-free counterparts, with the abundance of each cell type assessed each day over multiple days. Preliminary results confirm that the prion-containing cells out-compete their prion-free counterparts in the presence of the fermentable carbon source: glucose, whereas; it is the opposite result in the presence of the non-fermentable carbon source: glycerol.
Wike, Richard, "Investigating the Cellular Control and Biological Consequences of Prion Formation in Yeast" (2019). Biochemistry and Molecular Biology Summer Fellows. 17.