Proteins are large molecules that play many essential roles in the body. They do most of the work inside cells and are necessary for the structure, function and regulation of all tissues and organs. TDP-43 is a protein that is usually found inside the cell nucleus. However, in most people with ALS, it is located outside the cell nucleus in the cytoplasm of motor neurons.
Tags called small ubiquitin-like modifiers (SUMOs) can change how proteins function and where they are located in a cell. Scientists have also found SUMOs on TDP-43 protein, but nobody knows yet how these tags might change TDP-43 structure, location, or function.
With this grant, Terry Suk will investigate exactly where SUMOs tag TDP-43 and how they affect its behaviour using fruit fly models. He will also examine donated post-mortem spinal cord tissue from people who had ALS to learn about the extent of SUMO tagging of TDP-43 in ALS disease processes.
New learning about how SUMO tagging affects TDP-43 and ALS disease processes may lead to a new therapeutic target for ALS in the future.