Zink, Samantha
Mentor: Dr. Jose Rodriguez
My research interests span the landscape of protein structure and function, where amyloids present a unique platform for evaluating non-canonical structure-function relationships. Amyloids not only adopt ordered and disordered forms, they can also be both toxic or beneficial to cells. This begs the question: why are some amyloid conformations functional while others are cytotoxic?
The human gastrointestinal (GI) tract presents a unique environment for dissecting the nexus between pathogenic and functional amyloids. The gut microbiome produces the functional amyloid curli, that can be present on the surface of enteric bacteria. In cases of idiopathic Parkinson’s disease (PD), the protein alpha-synuclein is found aggregated within the enteric nervous system in early stages of the disease. Progressive disease stages are associated with an ascending, prion-like spread of aggregated alpha-synuclein into the central nervous system. Growing evidence supports the notion that certain amyloid proteins can facilitate the growth of other amyloid proteins and studies in mice suggest that the presence of curliated bacteria in the GI tract may enhance the aggregation of alpha-synuclein. The molecular drivers of this proposed interaction, however, are unknown.
Through the use of complementary structural and computational techniques, I am working towards developing a deeper understanding of how properties at the atomic scale exert their influence at the physiological level. To do this, I use cryoEM to better understand the molecular structure of curli and alpha-synuclein fibrils. In addition, I am developing computational methods to gain insight into the cross-seeding mechanism between these two proteins. Finally, I am building a computational pipeline to better understand features important for amyloid folds to use in designing new amyloids and predicting final amyloid folds.
