Our group is broadly interested in understanding how cells fold complex proteins, as well as in the design and application of next-generation in vivo directed evolution platforms. In recent work, we used chemical genetic tools for controlling mammalian proteostasis networks to reveal that RNA viruses hijack host chaperones to facilitate their rapid evolution. This phenomenon has proven broadly significant for understanding viral adaptation and pathology. More recently, we discovered that host protein quality control mechanisms (as opposed to folding chaperones) can have the opposite effect on viral evolution -- effectively constraining viral mutational space. The connections drawn between host proteostasis and viral evolution have potentially significant implications for topics including viral host-switching, vaccine development, and the design of improved antiviral therapeutic strategies. Moreover, these principles may provide strategies to turbo-charge directed evolution campaigns aimed at the development of new biotechnologies.

Matthew Shoulders (Massachusetts Institute of Technology)