$125,000 awarded to Dr. Dale Martin, University of Waterloo, in collaboration with Dr. Max Rousseaux, University of Ottawa, and Dr. Christine Vande Velde, Université de Montréal.
In over 97 per cent of all ALS cases, a protein called TDP-43, typically found within the nucleus of a cell, becomes trapped outside in the cytoplasm, forming clumps or aggregates. While mutations in the TDP-43 gene are responsible for this dysfunction in a small subset of cases, the cause for the majority of people living with ALS is still unknown. Therefore, identifying cellular mechanisms that regulate TDP-43 biology is key to uncovering disease processes in most cases.
Recent research has uncovered a specific cellular process called palmitoylation, which appears to play a significant role in TDP-43 biology. Palmitoylation involves the addition of a small tag to a protein that can influence how it functions and where it is located within a cell. Preliminary results indicate that TDP-43 undergoes palmitoylation in cells, and that this may contribute to the cytoplasmic buildup and aggregation often observed in ALS.
With this award, Dr. Martin seeks to better understand how palmitoylation regulates TDP-43 localization, function and aggregation using both cellular and animal models of ALS. By identifying the proteins that regulate this process, the team hopes to uncover new therapeutic targets for ALS. Ultimately, their goal is to design new therapeutic interventions that can correct TDP-43 dysfunction, which is of great interest as the outcomes from this study could advance our understating of almost all cases of ALS.