Characterize how chemical signals promote protein misfolding in neurodegenerative diseases

My group is using quantitative biophysical measurements and system level assays to establish a direct link, at the molecular level, between copper exposure and prion pathology. Copper exposure has previously been linked to the neurotoxic aggregation of prion proteins; however, the mechanism of its action is unknown. Using single molecule measurements, we demonstrated that copper induces prion protein monomers to misfold into a high-affinity conformation before assembling into oligomers. The misfolded proteins served as seeds that impose their structures upon native prion proteins and template their aggregation. We also demonstrated that the copper induced oligomers mediate inflammation and degeneration of neuronal tissue (Science Advances 2016).