Grant: Project Grant

Protein folding and degradation are central to cell biology. An exquisite control of these processes is required to ensure the proper survival of the cell and the health of the organism. Protein misfolding and aggregation have been linked to many diseases including cancer, aging, and neurodegeneration. Maintaining protein homeostasis in the cell is mainly accomplished by a family of proteins termed molecular chaperones that assist in protein folding. My group identified a highly conserved protein complex, which we named the R2TP complex, that interacts with several other chaperones and adaptor proteins. R2TP acts as a scaffold for the assembly of other critical complexes in the cell. Hence, R2TP has a novel cellular activity dedicated to protein assembly. The aim of the proposed project is to determine the structure and mechanism of function of this complex using cell biological, biochemical, and structural approaches. Here, we will concentrate on the function of R2TP in the biogenesis of cilia, which is a critical sensory organelle of the cell. Understanding the function of R2TP should lead to new insights into the mechanisms that regulate cellular protein homeostasis. Importantly, the proposal will also lead to a better understanding of diseases caused by the loss of such regulatory mechanisms.