Abstract
Protein mislocalization and proteostasis deficiencies are two primary hallmark features of neurodegeneration. We have identified protein fatty acylation as a mechanism linking these two features by directing many neurodegenerative disease-causing proteins for degradation by autophagy. S-acylation is a process where a fatty acid moiety is added to proteins reversibly to promote dynamic membrane binding and localization. Autophagy is a critical biological process that removes damaged organelles and toxic and aggregated proteins from the cell by delivering them to the lysosome for degradation. Post-mitotic cells, including neurons, are particularly sensitive to dysfunctional autophagy. Many of the genes associated with neurodegeneration code for proteins that are either required for autophagy and/or are targeted to autophagy for their ultimate removal. In both instances, proteins mislocalize and accumulate in the cell. The Neurdyphagy (Martin) Lab is focused on identifying and characterizing S-acylated proteins in neurodegeneration. This talk will focus on key proteins involved in Huntington Disease (HD) and Amyotrophic lateral sclerosis (ALS).
Speaker
Professor, Dale Martin
Dale Martin is an Assistant Professor in the Department of Biology at the University of Waterloo and heads the Neurdyphagy Lab studying protein mislocalization and proteostasis deficiencies in Huntington disease (HD) and amyotrophic lateral sclerosis (ALS). He obtained his undergraduate degree in Biochemistry and Microbiology & Immunology at Dalhousie University. His co-op opportunities led him to study fat metabolism and protein structure and function. He completed his Ph.D. in the Department of Cell Biology at the University of Alberta studying protein lipidation during apoptosis. After identifying a new function of huntingtin, he joined the Hayden Lab at the University of British Columbia to studying fatty acylation and autophagy in Huntington disease. He continued his research briefly in Philadelphia at Temple University in the Shriners Hospitals Pediatric Research Center in Dr. Gareth Thomas’s lab developing high-throughput drug screens to identify small molecules that can be used to target fatty acylation to prevent nerve damage and promote nerve repair.