Abstract:

"Autophagy" refers to the uptake of cellular material in a double membrane vesicle for lysosomal degradation. Autophagy is conserved in eukaryotes as a mechanism for surviving starvation and clearing harmful materials, including damaged mitochondria. Defects in mitochondrial clearance by autophagy, known as "mitophagy", are implicated in Parkinson's disease. Autophagy is initiated by the ULK1 protein kinase complex and the class III PI 3-kinase complex I (PI3KC3-C1). The structure and activation of the ULK1-PI3KC3-C1 supercomplex will be described. Rab GTPases, notably Rab1 and Rab7, and their phosphorylation states, appear to play multiple roles in autophagy and mitophagy. One such mechanism, involving a Rab7 phosphoregulatory switch and modulators of the PI 3-kinase complex II, will be described.

Bio:

James ("Jim") Hurley is a professor in the Department of Molecular and Cell Biology at the University of California, Berkeley. He was born in Moscow (the city in Idaho, USA, not Russia), graduated in Physics from San Francisco State University, and obtained his Ph.D. in Biophysics from the University of California, San Francisco. He was a senior investigator in the intramural program of the National Institutes of Health from 1992-2013, and joined the faculty of the University of California, Berkeley in 2013. He has been elected to the U.S. National Academy of Sciences, received the Hans Neurath award of the Protein Society, and has been a team leader in the Aligning Science Across Parkinson's Collaborative Research Network since 2020.

Dr. Hurley uses structural biology, biophysics, biochemistry, and cell biology approaches to understand the structure and function of cell membranes in health and disease. He is known for his work on the structure and mechanism of the ESCRT membrane scission machinery, coated vesicle and endosome biogenesis, lipid transporters and second messenger systems, and the autophagy core complexes.

Dr. Hurley’s lab currently has four major projects in the general area of mechanistic membrane biology. He has a long-standing interest in the core mechanisms of autophagy, and is currently most focused on the structural and biophysical basis of mitophagy and its role in Parkinson’s disease. He is investigating the mechanism of membrane scission by ESCRT complexes in the contexts of HIV budding and release from infected cells, autophagy, and membrane repair. In a third project, the hijacking of coated vesicle trafficking by HIV is being worked out by structural, reconstitution, and live cell imaging approaches. He is also using structural and biochemical approaches to study the roles of the lysosomal signaling complexes in neurodegenerative diseases, including mTORC1 and C9orf72.