Granule Up! Stabilizing stress granule formation to promote cell survival in ALS

When stressed, healthy cells produce stress granules, which are structures that protect vulnerable RNA molecules, that play a vital role in translating genetic instructions and overseeing protein production. ALS places constant stress on motor neurons, the nerve cells responsible for voluntary muscle movement, causing them to deteriorate and die. Recent evidence suggests that the disruption of proper stress granule dynamics may play a central role in the processes underlying ALS.

G3BP1 is an essential protein in the assembly of these stress granules. It is speculated that another important protein, TDP-43, helps to stabilize the production of G3BP1. In the majority of people living with ALS, TDP-43 levels and normal function are affected, thus impacting the cell’s ability to produce G3BP1 and disrupting stress granule formation. In her research project, Mariam aims to explore the use of antisense oligonucleotides (ASOs) designed to stabilize G3BP1. By reinforcing the cellular response to stress, this strategy could potentially improve cell survival in ALS models. Additionally, she also aims to uncover new functions of G3BP1 and how it differs from another related protein, G3BP2, which does not rely on TDP-43 for its normal production. Through these important experiments, it is hoped that Mariam’s research will pave the way for new therapeutic strategies that target stress pathways in ALS.

Extensive research investigating stress granules in ALS has been funded through the ALS Canada Research Program, with each grant bringing us closer to a potential new therapeutic avenue. Mariam’s supervisor, Dr. Christine Vande Velde, is a renowned researcher, internationallyrecognized in the ALS field who has been supported multiple times. Read more about her lab’s work here.