$75,000 awarded to Belay Gebregergis, a PhD student in Dr. Janice Robertson’s lab at TANZ CRND and LMP, University of Toronto.
In 2011, scientists discovered that mutations in the C9orf72 gene are the most common genetic cause of ALS. These mutations result in reduced levels of normal C9orf72 protein within cells, while also promoting the formation of additional toxic substances. But exactly how these changes contribute to causing ALS is not fully known. To determine how reduced levels of C9orf72 protein may cause disease, researchers must first understand its normal function in cells.
Previously, Dr. Robertson’s lab showed that decreased C9orf72 levels in mice can lead to increased levels of another receptor protein, called GluA1. Other evidence suggests that C9orf72 may play a role in the movement, or trafficking, of proteins within cells, such as GluA1. This abnormal biology and increased levels of GluA1 caused by reduced levels of C9orf72 may ultimately make motor neurons more vulnerable to glutamate excitotoxicity, a cell death pathway thought to play a role in ALS.
With this award, Belay aims to study the consequences of increased GluA1 levels and determine how this may lead to glutamate excitotoxicity in mice that have C9orf72 removed. He will also investigate the mechanisms underlying GluA1 trafficking in motor neurons from these mice, and the potential role of C9orf72 in the process. This work will help researchers to better understand the link between C9orf72 and GluA1 trafficking in cells, as well as the mechanisms that underly the observed excitotoxicity which could help to identify new therapeutic targets.