$50,000 awarded to Sonja Di Gregorio, a PhD student in Dr. Martin Duennwald’s lab at Western University.
Proteins are the substances responsible for almost all cellular functions and are often called the workhorses of the cell. To perform their tasks in the body correctly, proteins must first fold into the right 3D shape. Misfolded proteins, those that do not adopt the correct shape, can be harmful to cells. The body uses a variety of “quality control” mechanisms to help misfolded proteins refold into the right shape or destroy them before they can pose a threat. In some cases, however, these quality control mechanisms fail to prevent misfolded proteins from accumulating, which can cause cells to die. Protein-misfolding processes have been associated with a variety of different neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and ALS.
Sonja Di Gregorio, a PhD student in Dr. Martin Duennwald’s lab at Western University, is studying how the misfolding of three ALS-associated proteins —TDP-43, FUS/TLS and RGNEF — affects the quality control mechanisms of cells, and why protective processes fail in ALS. Using yeast cells that have been altered with genetic mutations linked to ALS, she will investigate how accumulated misfolded proteins lead to cell death. She will also study the biological properties of RGNEF, a protein only recently linked to ALS, to identify how mutations in this protein may lead to the development of ALS. For this part of the project, Di Gregorio will use yeast models, animal cell models and post-mortem human tissue samples. Findings from this project may provide a new target for the development of ALS treatments.