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Researchers at the University of Waterloo will use a CA$125,000 (about $93,000) grant from the <a href="https://als.ca">ALS Society of Canada</a> and <a href="https://braincanada.ca/">Brain Canada</a> to better understand how proteins become misplaced in cells and build into the toxic clumps that mark <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
Led by Dale Martin, PhD, an assistant professor of biology, the team is conducting in-depth studies into fatty acylation, a molecular process in which proteins are tagged with certain fatty molecules so they can be shipped to specific locations within cells. The goal is to find new targets for <a href="https://alsnewstoday.com/als-treatment/">ALS treatments</a>.
When fatty acylation goes awry, it can ship proteins to destinations other than those intended, making these proteins perform their functions in the wrong place. Problems in fatty acylation also can stop damaged proteins from traveling to cellular disposal sites, causing a toxic buildup that contributes to neurodegeneration.
Martin’s <a href="https://neurdyphagylab.squarespace.com">NeurdyPhagy lab</a> has been focusing on understanding how fatty acylation works, and how it might be involved in ALS.
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<h3>ALS Society, Brain Canada awarded two-year grants to eight research teams</h3>
In 2022, Lucia Liao, a PhD student at Martin&#8217;s lab, secured an ALS Canada–Brain Canada <a href="https://alsnewstoday.com/news/als-society-canada-brain-canada-early-stage-research-grants/">PhD grant worth $75,000</a>  to <a href="https://als.ca/research/als-canada-research-program/projects-funded/projects-funded-2022/">study how a type of fatty acylation</a> called palmitoylation contributes to the TDP-43 protein forming toxic clumps, a feature seen in nearly all ALS patients.
“These research funds will help us delve deeper into some of the earliest molecular mechanisms that go awry in ALS and set the foundation for continuing ALS research in the NeurdyPhagy lab,” Martin said in a <a href="https://uwaterloo.ca/science/news/professor-dale-martin-receives-grant-explore-new-therapeutic">university press release</a>.
To date, the lab reports having &#8220;pinpointed key proteins involved in ALS that undergo acylation.&#8221;
<a href="https://alsnewstoday.com/causes-of-als/">ALS occurs</a> when motor neurons — the nerve cells that control voluntary movement — become damaged, causing <a href="https://alsnewstoday.com/symptoms-of-als/#Muscular_symptoms">disease symptoms</a> characterized by progressive and bodywide muscle weakness.
An ALS hallmark is the buildup of misfolded proteins that are toxic to these neurons. This is thought to happen, at least in part, by key proteins being misdirected to sites within the nerve cells.
For example, the TDP-43 protein is normally found within the cell nucleus. But in ALS it tends to accumulate in the cytoplasm, the semifluid substance that fills a cell outside its nucleus, where <a href="https://alsnewstoday.com/news/structure-tdp-43-protein-aggregates-characterize-als-identified-first-time/">TDP-43 forms toxic clumps</a> that prevent motor neurons from working properly.
While fatty acylation influences where proteins are located within cells, tagging proteins with fat can be undone to allow a proper redirection. Identifying what controls this switch may led to targets for therapies able to slow or stop <a href="https://alsnewstoday.com/stages-of-als/">ALS progression</a>.
“We’re grateful for this funding and I’m excited to provide an update to the ALS community at the ALS Canada Research Forum in April,” Martin said. The ALS Canada meeting is to take place on April 27–29 in Toronto.
Martin is one of eight researchers nationwide to win a two-year ALS Canada–Brain Canada 2023 Discovery Grant, for a total awarding of CA$1.35 million to support a range of work into ALS causes, diagnosis, and treatment.
“These projects represent Canada’s best new ideas to impact our current understanding of ALS,” David Taylor, PhD, vice president of research and strategic partnerships at ALS Canada, said in a <a href="https://braincanada.ca/announcements/discovery-grants-2023/">press release</a> from the nonprofit organization. “Our hope is that discoveries made through this funding will take us closer to effective treatments and, someday, a world free of ALS.”

ALS Society-Brain Canada grant aids work into protein clumping in ALS

The <a href="https://als.ca/">ALS Society of Canada</a> (ALS Canada) and <a href="https://braincanada.ca/">Brain Canada</a> are collaboratively investing CA$1.4 million (about $1.1M US) in nine grants for studies ranging from the development of new treatments for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) to finding ways to predict disease progression.
The ALS Canada <a href="https://als.ca/research/apply-for-funding/">Discovery grant program</a> supports projects that seek to identify causes of the neurodegenerative disorder, treatments for ALS or related diseases, and ways for patients to live optimally.
This funding round also received financial support from the <a href="https://sla-quebec.ca/en/jean-pierre-canuel-order-break-ice-need-find-cure/">Dr. Jean-Pierre Canuel Fund</a> at the nonprofit patient support organization <a href="https://twitter.com/sla_als_quebec?s=11&amp;t=kNsxGZs4Wc2EGxGFgQSySQ">SLA Quebec</a>.
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<h3>Grant projects chosen after competitive peer-review process</h3>
“The Discovery Grant program continues to support critical Canadian research that contributes to the global effort on understanding and treating ALS,&#8221; David Taylor, PhD, vice president of research and strategic partnerships at ALS Canada, said in a <a href="https://www.globenewswire.com/news-release/2023/03/22/2632250/0/en/ALS-Canada-and-Brain-Canada-invest-more-than-1-4-million-in-ALS-research-grants.html">press release</a> from the organization.
&#8220;Over the past 15 years, many discoveries made with these funds have provided a foundation for studies that are impacting humans today, whether through clinical trials or critical initiatives like CAPTURE ALS,” Taylor said.
Of note, CAPTURE ALS is a Canadian-based platform that enables ALS researchers to share common resources, including vast amounts of data from ALS patients.
Grant projects were chosen following a competitive peer-review process in which global ALS experts considered each applicant’s merit, the project’s quality, and the potential to advance the field of ALS research.
As part of the partnership’s commitment to back more ambitious research, the Discovery grant program includes two CA$300,000 funding opportunities, an increase from the CA$125,000 at which additional projects had been funded.
[quote=&#8221;center&#8221;]The Discovery Grant program continues to support critical Canadian research that contributes to the global effort on understanding and treating ALS.[/quote]
<h3>List of grant recipients</h3>
This year, one of the CA$300,00 Discovery grants went to Alex Parker, PhD, of the Universite de Montreal, and Gary Armstrong, PhD, of McGill University, to study whether axon protection could be a promising ALS treatment strategy. Funding for this particular project came from two CA$150,000 contributions from Brain Canada and SLA Quebec.
The other grant went to Richard Robitaille, PhD, Danielle Arbour, PhD, and Roberta Piovesana, PhD, of the University of Montreal, and Robert Bowser, PhD, of the Barrow Neurological Institute, who will use their CA$300,000 award to study whether neuromuscular junction proteins could aid in the development of ALS biomarkers.
Recipients of the CA$125,000 Discovery grants:
<ul>
<li>Carlos Rodrigo Camara-Lemarroy, MD, and Minh Dang Nguyen, PhD, both of the University of Calgary, and Deepak Kaushik, PhD, of the Memorial University of Newfoundland, will study whether a certain routine and inexpensive procedure could have a neuroprotective effect in ALS.</li>
<li>Renee Douville, PhD, of the University of Winnipeg, Jody Haigh, PhD, of the University of Manitoba, and Domenico Di Curzio, PhD, of St. Boniface Hospital Albrechtsen Research Centre will investigate the potential role of retroviruses using a new mouse model of ALS.</li>
<li>Thomas Durcan, PhD, and Yasser Iturria-Medina, PhD, both of McGill University, will study whether a new three-dimensional cell culture model can help predict ALS progression.</li>
<li>Gary Shaw, PhD, and Martin Duennwald, PhD, of Western University, and Elizabeth Meiering, PhD, of the University of Waterloo, will determine if improving the mechanisms of toxic protein disposal in motor neurons can become a treatment strategy.</li>
<li>Maria Stepanova, PhD, in collaboration with Holger Wille, PhD, of the University of Alberta, will use their grant to examine the potential for computational methods to aid in the design of antibodies for ALS diagnosis and treatment.</li>
<li>Christine Vande Velde, PhD, of the Universite de Montreal, and Marlene Oeffinger, PhD, of the Institut de recherches cliniques de Montreal will investigate if restoring G3BP1 levels could be a promising ALS treatment strategy.</li>
<li>Maria Vera Ugalde, PhD, and Heather Durham, PhD, of McGill University, will study whether a novel way of viewing certain protective proteins could better explain their role in ALS.</li>
</ul>
“These nine leading-edge projects led by teams across Canada are contributing to global scientific discovery,” said Viviane Poupon, PhD, Brain Canada president and CEO. “Our unique partnership with ALS Canada has the potential to lead to better diagnosis and treatment for people living with ALS, and it’s something that we are very proud of.”

Tag: Brain Canada

ALS Society-Brain Canada grant aids work into protein clumping in ALS

ALS Canada, Brain Canada to fund more than $1M in research grants