Wisdom of the Crowded: Marrying theory and experiment to tackle protein folding problems in live cells

For decades, our basic notion of how proteins fold has been rooted in the Anfinsenian idea that sequence determines structure reversibly through the preference of a native state at thermodynamic equilibrium.  In the present day, advances in our understanding of biochemistry and cell biology have suggested such a view of folding may apply as an exception more than a rule: many proteins require help from ATPase chaperones in order to fold, and modulate their folding state substantially depending on their available interaction partners.  Proteins also frequently become irreversibly trapped in non-functional aggregates, and the cell must deploy an elaborate quality control machinery to prevent aggregation from getting out of hand.  In all of these cases, it is necessary to think beyond the physics of thermal equilibrium in order to make sense of folding in the cell. This talk will consist of several vignettes about chaperones, aggregation, and cellular protein quality control where nonequilibrium ideas about the folding and transport of proteins yield insight into experimental results both in vitro and in vivo.