Correct protein folding and quality control are essential for normal cellular function. The accumulation of misfolded proteins is emerging as central to a wide range of disease states, including many neurodegenerative disorders such as Huntington’s and Prion Disease. A complex network of molecular chaperones facilitate protein folding and assembly and monitor all aspects of protein homeostasis. Chaperones assist the folding of newly translated and stress-denatured proteins, as well as affects protein quality control. 

Our research investigates the mechanisms and pathways by which chaperones carry out these diverse functions. Systems approaches identified a chaperone network linked to the protein synthesis apparatus assists protein biogenesis. The emergence of this translation-linked chaperone network likely underlies the elaborate co-translational folding process necessary for the evolution of larger multidomain proteins characteristic of eukaryotic cells. A stress-inducible chaperone network protects cells from environmental stress and assists quality control. These chaperones also communicate with the ubiquitin-proteasome pathway to clear misfolded proteins from the cell. Protein quality control in the eukaryotic cytosol relies on the sequestration of misfolded cytosolic proteins in specific quality control compartments. Our studies of chaperone function provide a framework to understand the link between protein misfolding and human disease.