Protein folding and misfolding | Prions | Chaperones | Amyloid | Cellular Proteostasis | Degenerative neuromuscular disease mechanism
Protein misfolding and aggregation are implicated in a wide array of human diseases. We are interested in how protein aggregates and amyloid cause toxicity to cells. We have a longstanding interest in prion strains and amyloid formation. We use the yeast model system to discover novel effectors of amyloid propagation through genetic screens. Our screens have implicated specific co-translational chaperones in amyloid-associated toxicity. We are also investigating how mutations in chaperones cause disease. Mutations in an HSP40 chaperone cause a form of muscular dystrophy. Our biochemical analysis of disease-causing mutants, coupled with suppressor screens, has led to a better understanding of the underlying disease mechanism, and provides new clues for possible therapeutic intervention. This work is done in collaboration with colleagues here who treat patients with neuromuscular diseases.