$75,000 awarded to Charlotte Manser, a PhD student in Dr. Derrick Gibbing’s lab at the University of Ottawa.
Stress granules are 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. Once the stress passes, the stress granules break apart and RNA resumes its work within the cell. Recent evidence suggests that disruption of proper stress granule biology may play a central role in ALS disease processes.
In this study, Charlotte will investigate how various ALS-linked genes influence stress granule dynamics within cells and how this may impact the mislocalization of TDP-43, an ALS-linked protein known to become trapped in abnormal stress granules. Once she has identified the genes that have a significant effect, Charlotte will validate her findings in motor neurons derived from stem cells. Finally, using a mouse model of ALS, she will explore the mechanisms by which these gene candidates alter stress granule dynamics and TDP-43 function.
By systematically investigating the role of various ALS-linked genes in key disease processes, this work will help to increase our understanding of the biological pathways that underly ALS. The information gained from this study should provide valuable insight into the cellular processes that take place when stress granules assemble and disassemble, which is essential to developing future treatments aimed at maintaining healthy stress granule dynamics and ultimately slowing or stopping the progression of ALS.