$125,000 awarded to Dr. Xavier Roucou, at l’Université de Sherbrooke.
Conventional science assumes that the known genes in our DNA contain coding information, with a single start and end, which produces a single protein with specific function that is critical for a cell to survive. However, Dr. Xavier Roucou has discovered that some genes may also contain a hidden set of instructions that make what are called alternate proteins (altProts). AltProts are not just variations of the expected proteins; they are entirely different.
Abnormal FUS protein has been identified as one of the causes of familial ALS, the inherited form of the disease. Dr. Roucou and colleagues recently discovered a new altProt created from a piece of DNA within the FUS gene, called altFUS, and believe that it may be a unique driver of the disease. They found that in ALS, alt-FUS cooperates with FUS in three processes within neurons: (1) by altering the energy-producing structures called mitochondria; (2) by impairing the ability to clear out waste products in a process known as autophagy; and (3) by encouraging FUS proteins to accumulate. Notably, they found that some of the problems related to ALS only occurred when both FUS and altFUS were present.
With this grant, Dr. Roucou will look for differences in altFUS protein in human ALS by comparing post-mortem brain tissue with and without the disease. Next, he will investigate if altFUS contributes to ALS on its own, by examining if abnormal forms of altFUS can cause disease in cells and fruit flies in the absence of full length FUS protein. Throughout his research, Dr. Roucou will add the altProt data generated in this project to his recently created open source database called OpenProt, which is freely available to other researchers online, in order to share his research and make it available to other investigators.
If altFUS is observed to be a key contributor to developing ALS, this project could revolutionize the biological understandings of the disease. The insights gained may highlight the importance of exploring altProts in other ALS-related genes, especially since alternative protein-coding instructions have been found on 75 per cent of the top 50 ALS-related genes.