$75,000 awarded to Donovan McDonald, a PhD student in Dr. Martin Duennwald’s lab at Western University
DNA holds the master code of genetic instructions that oversee the production of proteins, the workhorses of the cell. Proteins consist of long chains of smaller units called amino acids. The genetic information carried in our DNA is converted into proteins at a specific structure within the cell, called the ribosome. Other molecules, called tRNA, play a key role in protein formation by delivering amino acids to the ribosome to be incorporated into proteins. New evidence suggests that abnormal functioning of tRNA may contribute to errors in protein formation that lead to protein misfolding, a common feature seen in many neurodegenerative diseases, including ALS.
With this award, Donovan will investigate the effects that abnormal tRNA function have on TDP-43, a protein known to be affected in nearly all ALS cases. Using a yeast model, Donovan will first explore how a common mutation in tRNA contributes to the misfolding of TDP-43. Then, he will determine how genes known to regulate tRNA function influence TDP-43 dysfunction. Finally, he will investigate how a specific protein associated with a familial form of ALS, called angiogenin, influences tRNA and subsequently TDP-43.
The abnormal functioning of tRNA has not been well studied in ALS to date. It is clear that tRNAs perform many functions in cells that, if interrupted, may contribute to disease. The results of this work will add another piece to the ALS puzzle, providing new knowledge in a previously unexplored area. Additionally, this work could help to identify new risk factors, biomarkers, and possibly new treatment targets for ALS.