How are Phosphates Removed from Tau?
Co-Principal InvestigatorsDaniel Southworth, PhD
We will characterize the complex of Hsp70-PP5 that removes phospho groups from tau. We will use structural biology methods to explore the structure of the Hsp70-PP5 structure and its interactions with tau. In addition, we will use chemical biology approaches to map the protein-protein interactions between Hsp70 and PP5, towards building molecules that might promote this interaction.
While there has been extensive work to understand how tau is hyper-phosphorylated in AD, less attention has been spent on exploring the mechanisms of de-phosphorylation. Because tau modification is a balance of these two processes, we seek to develop a structural and mechanistic understanding of the de-phosphorylation process.By better understanding the mechanisms of tau de-phosphorylation, we hope to uncover new drug targets or opportunities for promoting this activity.