Some proteins help other proteins fold into their normal shapes. We study how these so-called protein chaperones act in the reproduction of prions—infectious, misfolded proteins. This protein misfolding problem is related to a similar occurrence seen in many human diseases.
Before a protein can do its work, it folds into a 3-dimensional shape. Although most proteins fold into this shape on their own, some require the help of protein chaperones to fold properly. Chaperones guide newly made protein molecules into their correct shape and prevent improperly flded proteins from aggregationg and causing toxicity. Mutations in chaperones strongly influence how misfolded proteins make cells sick.
We use genetics, molecular biology, and biochemistry to study prions of yeast cells to understand how chaperones modify the growth of fibrous masses called amyloids. Amyloid masses form toxic deposits are connected with the death of tissue in many human disorders, including type 2 diabetes and Alzheimer’s disease.
Our studies suggest that altering fucntions of chaperones can either increase or decrease the ability of amyloid to propagate in cells. Our findings are providing information on how chaperones influence amyloid propagation and on how chaperones and proteins that cooperate with them carry out their many important functions in the cell.