Triggers and interactions of protein aggregates

Protein aggregation has been associated with an ever growing list of diverse human diseases, ranging from type II diabetes to Alzheimer disease and is mediated by the formation of intermolecular beta structure by short aggregation prone regions of the polypeptide sequence of the aggregating proteins. In order to direct discovery of novel aggregating proteins in disease settings where they currently not known, I want to enhance computational methods to identify the conformational triggers that convert a protein from its globular native form into its aggregated state. This approach has already led me to identify p53 aggregation as a tumor promoting mechanism in cancer. Second, I want to develop methods to predict the biological reactivity of protein aggregates based on their interactions with other cellular factors.