Myriam Gagné was not expecting to work on ALS research. But the first time she saw Dr. Christine Vande Velde’s lab at l’Université de Montréal, it was “love at first sight.” Studying ALS would allow her to combine basic cell biology, neurosciences and biochemistry, her main academic areas of interest. She joined the lab in 2016.
One year later, as a master’s student, Gagné was working on a project that involved studying a potential biological process related to one of the genetic causes of ALS — whether misfolded SOD1 protein disrupts the turnover of the power generators inside cells, called the mitochondria. Her findings were inconclusive, which was disappointing.
“This was the first time in my scientific career that I faced adversity,” said Gagné. “Dr. Vande Velde reassured me that in science, negative results sometimes happen, even with valid hypotheses, and the learning is still valuable. The experience gave me a sense of urgency and a broader understanding of ALS as a research area.” Reporting negative findings is just as crucial as reporting positive findings, especially in ALS research.
Dr. Vande Velde offered Gagné an opportunity to work on a different project that was funded by ALS Canada that had been awarded to Dr. Vande Velde in 2018. The project involves studying the behaviour of a newly-discovered protein called hnRNP A1B.
Thanks to a $75,000 Trainee Award from the ALS Canada Research Program, in partnership with La Fondation Vincent Borque and Brain Canada, Gagné is receiving multi-year salary support to work on this project.
Fishing for a function
Since the actual name of this protein — heterogeneous nuclear ribonucleoprotein A1B (hnRNP A1B) — is quite long, Gagné and her lab colleagues call it “A1B” for short. It is a “cousin” of TDP-43, a protein that behaves abnormally in almost all cases of ALS by moving out of the nucleus of motor neurons and forming clumps in the cytoplasm.
Dr. Vande Velde and her team discovered that A1B might also be involved in ALS disease processes. They found that people with ALS have more A1B in their motor neurons and that it tends to clump in the cytoplasm when TDP-43 behaves similarly.
Gagné has carefully planned cell and mouse studies to learn how these two proteins and their behaviours may be related in ALS. She will look for A1B in normal cells and ALS cells to determine where A1B is located in the central nervous system and whether the levels increase with age. Finally, Gagné will “fish for the function” of A1B by working closely with Dr. Marlene Oeffinger, at the Institut de recherches cliniques de Montréal (IRCM), an expert in how proteins interact with each other.
If Gagné discovers new insights into the behaviour and function of A1B and how it relates to TDP-43 abnormalities in ALS, she will look for the same relationships in ALS spinal cord samples. Dr. Janice Robertson at the University of Toronto is providing the human tissue samples generously donated by people who had ALS.
Keen to advance ALS research
Gagné hopes that learning about the role of A1B in ALS will lead to a better understanding of ALS disease processes and potential targets for the development of new therapies in the future. Measuring A1B levels could also be a possible way to identify abnormal TDP-43 protein behaviour, which would make it a valuable biomarker to monitor disease onset or progression of ALS in humans.
One day, she hopes to lead her own lab. “I can relate to the urgent need for answers for people living with ALS and their families,” Gagné said.