$125,000 awarded to Dr. Maxime Rousseaux, University of Ottawa, in collaboration with Dr. Martin Duennwald, Western University.
TDP-43 is a protein that is normally found inside the nucleus of a cell. However, in over 97 per cent of people with ALS, TDP-43 becomes trapped outside the nucleus in the cytoplasm where it forms aggregates or clumps. Unlike many other ALS-linked genes, however, mutations in the TDP-43 gene are responsible for this dysfunction in only a small subset of cases, with the cause for most people living with ALS still unknown.
Tags called small ubiquitin-like modifiers (SUMOs) can change how proteins function and where they are located in a cell. When SUMOs attach to proteins, that process is called SUMOylation. Scientists have found SUMOs on TDP-43, but nobody knows yet how these tags might change the structure, location, or function of the protein.
With this award, Dr. Rousseaux and his team aim to investigate the link between TDP-43 and SUMOylation in ALS, using a new mouse model generated in their lab. The team will investigate how SUMOylation occurs in the cell, how blocking the SUMOylation of TDP-43 may alter its activity, and whether SUMOylation can influence ALS disease processes.
Understanding how TDP-43 dysfunction could be regulated through SUMOylation is of great interest as the outcomes from the study will impact almost all people living with ALS and could open up new avenues of exploration for developing treatments targeting TDP-43.