Matthew D. Shoulders, the Whitehead CD Associate Professor of Chemistry at the Massachusetts Institute of Technology, will deliver a seminar entitled, "Protein Folding Challenges in Biomolecule Assembly and Evolution." Hosted by Paramjit Arora.
For more information about the speaker, click here.
Abstract: Abstract: Our group is broadly interested in understanding how cells fold complex proteins. The development of chemical genetic techniques to allow precision engineering of proteostasis network composition and activities will be discussed. Applications of these techniques have enabled a variety of advances related to the folding and quality control of large extracellular matrix proteins such as collagen, leading to the discovery of a molecular code that controls assembly of the fibrillar collagens. Progress in understanding the roles of proteostasis in evolution at the host-pathogen interface will also be presented. We used deep mutational scanning on influenza nucleoprotein to systematically and quantitatively evaluate the roles of host chaperones and the heat shock response in defining the fitness of >106 possible nucleoprotein sequences. We found that the depletion of a select suite of host chaperones using a custom-designed HSF1 inhibitor has striking effects on nucleoprotein mutational fitness at restrictive temperatures that mimic fever, whereas HSF1 inhibition has no effects at permissive temperatures. Of particular note, host chaperone depletion very strongly reduces the ability of influenza to escape innate immune system factors. The connections drawn here between host proteostasis and viral evolution have potentially important implications for numerous relevant issues, including viral host-switching, vaccine development, and the design of improved antiviral therapeutic strategies.