Investigation of the interplay between stress and genetics in ALS

Dr. Vande Velde’s lab and her team have been investigating whether reduced levels of TDP-43 in the cell nucleus, as commonly seen in ALS, causes reduced levels of another protein called G3BP1. It is an essential protein for the formation of stress granules, protective structures that healthy cells make when they are exposed to environmental stress. Stress granules protect vulnerable RNA, molecules that translate genetic instructions and oversee protein production from becoming damaged. In ALS, disruption of proper stress granule biology appears to play a central role in the disease process. So far, the research on these structures has largely been conducted in cell studies.

With this grant, Alicia Dubinski will be among the first researchers to look at stress granule processes in an ALS animal model. She will apply mild heat to TDP-43 model ALS mice, similar to placing them in a warm sauna, and examine how the disease processes affect the formation of stress granules. She will also investigate how aging and being exposed to heat over time changes their ability to properly make stress granules.

This project builds on Dr. Vande Velde’s 2015 ALS Canada-Brain Canada Arthur J. Hudson Translational Team Grant. Continued support will allow Dubinski to shed light on how TDP-43 affects the formation of stress granules. New insights about this biological process may help identify new treatment targets for maintaining healthy formation of stress granules to halt or slow disease progression in ALS.