ASRC-CCNY Seminar Series in Biochemistry, Biophysics and Biodesign: D. Allan Drummond, University of Chicago

Abstract    Cells across the tree of life react to sudden maladaptive changes–stresses–in consistent ways. Proteins and mRNAs aggregate, most protein synthesis halts, and mRNAs encoding chaperones, long considered components of a protein-misfolding rescue system, are massively expressed and selectively translated. Heat shock, oxidative stress, starvation, and other so-called proteotoxic stresses trigger similar reactions, leading to the model that stress-induced formation of toxic misfolded aggregates is the central challenge met by cellular responses. However, evidence has mounted for a fundamentally different coexisting model: that cells use biomolecular condensation to sense and transduce stress, that condensation reorganizes the cell to redirect activity toward stress-appropriate programs, and that chaperones are major regulators of condensation. Rather than toxic aggregates, the central phenomena are adaptive condensates. I will discuss the unique aspects of adaptive condensation, both empirical and conceptual, with an emphasis on open questions.