Defining the RBP repertoires of ALS-associated membrane-less granules

DNA holds the master instructions for making proteins in the body. Other molecules called RNA are made from the master instructions and have several critical roles in cells, including being responsible for protein production. When cells are internally or externally exposed to potentially harmful factors, RNA is protected by specific proteins that bind it and accumulate in little structures called stress granules. Over the past several years, ALS researchers have learned that the composition, distribution and formation of stress granules within motor neurons are significant factors in the development of ALS and frontotemporal dementia.

With an ALS Canada-Brain Canada Discovery Grant awarded in 2016, Dr. Lécuyer used antibodies to explore and describe stress granules in greater detail. For this project, he will advance his previous work. Using the antibodies and advanced imaging techniques, he will investigate the relationship between stress granules and RNA binding proteins in different types of human ALS cells, with an emphasis on toxicity caused by the most prominent genetic form of ALS, C9orf72. Using these results, he will also examine how stress granules are associated with neurodegeneration in ALS by conducting experiments with fruit flies that have been genetically modified to have human ALS. An important aspect of this project is that Dr. Lécuyer will create an open ALS RNA Binding Protein Imaging Database to share his imaging data with the global ALS research community.