Protein-protein interactions in the early stages of amyloid assembly mechanisms

Over 50 human disorders involve the aggregation of proteins into amyloid plaques. These disorders include type 2 diabetes, Alzheimer’s and Parkinson’s diseases, as well as a host of rarer disorders, which all have no cure. The need to develop successful therapies for amyloid disease is a major priority for human health today. Amyloid formation is of intense interest both to academics focused on how changes in the sequence of a protein causes amyloid formation, and to pharmaceutical companies who want to design drugs that can prevent these diseases.

We will focus on two amyloid diseases – type 2 diabetes and dialysis-related amyloidosis, which involve the formation of amyloid deposits in different sites in the body. By combining structural molecular biology and chemical biology we will map the early processes that initiate amyloid formation and use the knowledge gained to create molecules able to control assembly by targeting these sites.

By testing the effects of this toolkit of reagents in cells and in model organisms we hope to reveal new understandings of why proteins aggregate and to develop new strategies to control aggregation-induced cellular dysfunction and disease.