What role does its sister protein play when restoring G3BP1 levels as a potential ALS treatment strategy?
Award: $125,000
Collaborators: Dr. Marlene Oeffinger, Institut de recherches cliniques de Montréal (IRCM)
Dr. Christine Vande Velde is a cellular biologist at the Centre de recherche du CHUM, Université de Montreal, and one of nine ALS Canada-Brain Canada Discovery Grant recipients for 2022. While she and her team spend their lab hours parsing out biological intricacies, her work is always motivated by something bigger: the lives of people affected by ALS.
Dr. Vande Velde just finished her six-year term on the ALS Society of Canada’s Board of Directors, which has given her face-to-face experiences with people living with ALS and their families.
“It’s been a fabulous experience that changed the way I think about what ALS Canada does. It has helped me always keep the mission front of mind,” she says.
For more than a decade, Dr. Vande Velde’s lab has been part of driving ALS research forward in Canada.
With this award, the research team will seek to understand the function of two “twin” proteins called G3BP1 and G3BP2. The proposal emerged from conversations between two trainees in her lab, a promising sign for the future of Canadian ALS research.
Conventional knowledge would say the two proteins are so similar, they’re identical. But other researchers have shown the prevailing narrative may be wrong, as previous studies reveal that when G3BP1 levels are reduced, G3BP2 cannot fully compensate for the loss.
G3BP1 tends to degrade when a protein called TDP-43 leaves its home in the nucleus – one of the most common hallmarks of ALS and other neurodegenerative diseases. Its twin, G3BP2, does not.
Dr. Vande Velde’s project asks a number of questions about what G3BP1 might do that its sibling can’t, if restoring G3BP1 function might be a therapeutic target for ALS, and more.
“In research, we can’t rely on overgeneralizations (like assuming two “twin” genes have the same function),” she says. “I’m excited to go deep into the biology to understand the nuances. In treatment, the details matter.”
“Regardless of the results, we will learn something about a target we think is druggable and relevant to the disease that we didn’t know before,” she says.