Alicia Dubinski may have inherited both her love for science and studying a neurodegenerative disease from her mother, a neuroscientist at the University of Toronto.

When Dubinski was still a graduate student at the University of Waterloo, she met Dr. Christine Vande Velde at l’Université de Montréal in the Spring of 2019. She knew right away that she wanted to join Dr. Vande Velde’s lab and work on ALS research for her PhD. Dr. Vande Velde was happy to recruit Dubinski after learning about her strong academic achievements.

Dr. Vande Velde and her team have been working on a large project funded by an ALS Canada-Brain Canada Arthur J. Hudson Translational Team Grant in 2015. They are investigating whether reduced levels of TDP-43 protein in the nucleus of motor neurons, an abnormal behaviour observed in almost all cases of ALS, leads to reduced levels of another protein called G3BP1.

Now, with a $75,000 Trainee Award from the ALS Canada Research Program, Dubinski is receiving multi-year salary support to work on expanded areas of investigation on this large project. She will be among the first scientists to examine the formation of stress granules in an ALS animal model. Most research on stress granules so far has involved cell studies.

“I hope to discover how environmental stress affects the ability of healthy motor neurons to form stress granules and how that could potentially lead to ALS,” said Dubinski. “New Insights from animal models may help identify new treatment targets for slowing or halting disease progression in people with ALS.”

Stress granules and TDP-43

Stress granules are protective structures that form in healthy cells to protect vulnerable RNA from becoming damaged from environmental stress, such as heat or pollution, for example. RNA are molecules that translate genetic instructions for protein production. The formation of stress granules “hits the pause button” to halt that process. Once the stress passes, the stress granules break apart, and RNA resumes its work.

Dr. Vande Velde and scientists working in her lab have observed that when TDP-43 leaves the nucleus of motor neurons and clumps in the cytoplasm in ALS, G3BP1 protein levels go down. G3BP1 protein is essential for the proper formation of stress granules, so when its levels decrease, stress granules may not be able to form correctly. As a result, motor neurons may be more susceptible to damage.

Collaborating to advance ALS research

To learn more about the biology of stress granule formation in ALS, Dubinski will perform a series of experiments with healthy mice and mice that have been genetically engineered to model human ALS with TDP-43 protein abnormalities. Dr. Kevin Talbot, at the University of Oxford, United Kingdom, is providing the mouse models. “If we don’t have the resources to do an experiment, Dr. Vande Velde finds another researcher and asks them to collaborate with us,” said Dubinski. “Dr. Talbot recently published a paper on this mouse model. Dr. Vande Velde was very excited about it because the mice express a level of TDP-43 protein that more closely mimics human disease than has been possible with previous mouse models. Dr. Talbot agreed to collaborate and sent us some mice.”

Dubinski will encourage the formation of stress granules by exposing the mice to a mild heat condition. She will look for differences in mice before and after symptom onset and with slowly progressing and quickly progressing ALS symptoms. Dubinski will also expose some mice to mild stress every six weeks for a few months to see how aging affects their ability to make stress granules. Finally, she will look for differences in stress granule formation in their brains and the spinal cords, to look for clues that might explain why some people with ALS also develop frontotemporal dementia.

Dubinski is also collaborating with Dr. Mohan Babu, who studies protein biology in ALS at the University of Regina and is a 2019 Project Grant recipient from the ALS Canada Research Program. Dubinski will analyze the interactions between TDP-43 and G3BP1 in the mouse models to see if other proteins play a role in the formation of stress granules. Understanding all of the cellular processes that take place when stress granules assemble and disassemble in ALS disease processes is essential for future work to develop new treatment targets.

Inspiration matters

Shortly after joining the Vande Velde lab, Dubinski had opportunities to meet patients, including at the Walk to End ALS in Montreal Quebec. “So many people came up to me to thank me. It was very humbling because I had only been working in ALS research for a short time,” Dubinski said. “I’m a scientist at heart but being able to interact with patients pushes me that extra mile, and I like that.”

The ALS Canada Research Program 

This funding represents one of 16 grants and awards we provided in 2019 through the ALS Canada Research Program, which is the only dedicated source of funding for ALS research in Canada.

ALS Canada Trainee Awards support Canada’s emerging ALS researchers, whether they are doctoral students, postdoctoral researchers, or clinical research fellows. Trainee awards encourage young researchers to choose ALS as their area of focus, helping to ensure that Canada has a strong base of talented ALS researchers today and into the future. They also ensure that important ALS work is being pursued by high quality young scientists.

The funding of the project followed a rigorous scientific assessment by a panel of ALS experts. The panellists evaluated a larger pool of applications to identify applicants that demonstrate scientific excellence and have the potential to most quickly advance the field of ALS research in order to develop effective treatments.

ALS Canada is a registered charity that receives no government funding. Everything we do – from funding research to providing community-based support for people living with ALS – is possible only because of donor generosity and partnerships with provincial ALS Societies who contribute to the ALS Canada Research Program.

Because of you, the ALS Canada Research Program can continue to fuel the scientific discoveries that further our understanding of ALS. Your support makes a difference.

Please consider making a donation to help create a future without ALS.

Posted in: Research