Protein Quality Control (PQC) is important for cellular function and implicated in human diseases, including cancer and neurodegeneration. PQC pathways include molecular chaperones that regulate protein folding and the Ubiquitin Proteasome System (UPS), which targets proteins for degradation. My group will study the chaperones involved in the pro-degradation pathway that directly target proteins to the proteasome. We will characterize these interactions using biochemical assays, single molecule FRET and cryo-electron microscopy. This work will provide insight into how chaperones and proteasomes interact in human disease, therefore identifying protein-protein interactions to target therapeutically. 

Biochemical analysis

We use in vitro biochemistry to study how chaperone proteins triage substrate proteins for degradation by the proteasome. Approaches include in vitro reconstitution of protein complexes, ubiquitination and degradation assays, and FRET binding experiments. We also employ single molecule FRET to study how the dynamic movements of chaperone proteins affect their activity and the outcomes on substrates.

Cryo-Electron Microscopy

Our group uses cryo-electron microscopy to determine high resolution structures of large protein complexes, including chaperones and the 26S proteasome. We aim to observe the hand off of ubiquitinated substrates from chaperone complexes to the proteasome to better understand this important PQC mechanism. We use the Titan Krios at the NextGen Precision Health Institute for data collection.