The biophysics and cell biology of protein misfolding diseases.
We conduct interdisciplinary studies of pathological protein misfolding in human disease, studies of unfolded proteins and protein folding, investigations of mechanisms of beta-cell death in diabetes, and studies of protein membrane interactions. Part of our work includes the development of new tools for the study of biomolecules. We also undertake efforts in protein engineering and design. Our work on pathological protein misfolding is focused on the process of amyloid formation. We study a fundamental issue in metabolic disease: pancreatic islet amyloidosis by the neuropancreatic hormone islet amyloid polypeptide (IAPP. also known as amylin); a process which leads to beta cell stress, dysfunction and death. We combine biochemical, biophysical and cell biological approaches and work closely with experts in transgenic mouse models of pancreatic islet amyloidosis and diabetes. We have recently significantly extended our work on amyloid formation to encompass investigations of amyloidogenic proteins with membranes and are studying the role of membrane asymmetry in protein-membrane interactions. Our studies of protein folding are directed at investigations of the unfolded state and its role in protein stability, folding and aggregation. This work includes experimental studies as well as molecular dynamics simulations and close collaborative efforts with theoreticians. Work on protein design focuses on the development of novel approaches to rationally improve the stability and solubility of proteins that hold promise for clinical applications. Part of our program involves the development of new tools and reagents to better facilitate investigations in the broader fields of protein structure, aggregation, folding and dynamics. g.
