Research

Research

Mechanisms of protein aggregation and self-assembly in multicomponent systems

Our current focus is on mechanistic complexities associated with aggregation of proteins with expanded polyglutamine tracts. This is directly relevant to Huntington’s disease and eight other neurodegenerative disorders. To understand how aggregation causes tissue-specific cell death we are starting to study mechanisms of protein aggregation in multicomponent systems. The goal is to understand the synergy between protein aggregation and pathways and processes that control cellular decisions. We use a combination of polymer theory, atomistic and mesoscopic simulations, and experiments in vitro and in cell culture.

Organization of interaction networks around disordered proteins

We have an active program focused on detailed investigations of the phase behavior of intrinsically disordered proteins (IDPs). Our goal is to understand how disorder i.e., a lack of well-defined three dimensional structure leads to specificity and fidelity in molecular recognition. A majority of the proteins involved in eukaryotic transcriptional regulation and signal transduction are IDPs. We are leveraging our fundamental understanding to facilitate de novo design of disordered regions. Since disordered regions are often at hubs of some the most important networks in biology, the ability to control disorder through sequence design should afford us the ability to rewire networks to control cellular phenotypes, a goal that has direct relevance for complex diseases such as cancers, cardiovascular disorders, and neurodegeneration.