$165,000 awarded to Dr. Hana Fakim, a postdoctoral fellow in Dr. Christine Vande Velde’s lab at CR-CHUM, Université de Montréal.
TDP-43 is a protein that behaves abnormally in the motor neurons of 97 per cent of people with ALS. It is usually found in the nucleus, but in people with ALS, it becomes trapped outside in the cytoplasm where it forms aggregates. Previous work in the Vande Velde lab showed that the mislocalization of TDP-43 to the cytoplasm also results in decreased levels of another protein, called G3BP1.
G3BP1 is an essential protein for the formation of stress granules, which are protective structures that healthy cells make when they are exposed to environmental stress. Stress granules protect vulnerable RNA (molecules that translate genetic instructions and oversee protein production) from becoming damaged. Recent evidence suggests that disruption of proper stress granule biology may play a central role in ALS disease processes.
With this award, Dr. Fakim will study the critical role that abnormal TDP-43 is thought to play in the regulation of G3BP1. Using cell culture and patient samples, Dr. Fakim will investigate whether G3BP1 levels are altered in the brains of people living with ALS and explore the biological mechanisms responsible for these changes. Additionally, antisense oligonucleotide (ASO) technology will be used to determine whether restoring normal levels of G3BP1 in mice can enhance cell survival. This work has important therapeutic potential for the significant percentage of ALS cases where TDP-43 abnormalities are present.