Dr. Maria Vera Ugalde: Exploring a cellular mystery: why our bodies “paramedics” don’t work well in motor neurons

Will this new way of looking at certain protective proteins better explain their role in ALS?  

Award: $125,000 

Collaborator: Dr. Heather D. Durham, McGill University 

Dr. Maria Vera Ugalde loves fundamental biology. As a biochemist at McGill University, she spends her days using advanced microscopy techniques to see into the intricate workings of our cells.  

As one of the 2022 ALS Canada-Brain Canada Discovery Grant awardees, she gets to take her expertise and apply it to a new field: ALS research.  

“I don’t usually do biomedical research – I usually do fundamental biology,” she says. “This project is really exciting because it allows my research to be more meaningful.”  

Her winning 2022 proposal focuses on something Dr. Vera Ugalde has studied since her earliest work as a researcher: heat shock proteins (HSPs).  

When a protein misfolds in our cells, they no longer do their jobs properly or may become toxic. Fortunately, our bodies don’t leave us hanging: they deploy HSPs, our cellular “paramedics,” to come refold the misshapen protein and help get the cell running again. This process supports protein homeostasis, critical for the balanced, healthy functioning of our cells. 

Unfortunately? One type of cell is particularly bad at inducing HSPs in times of stress, even in healthy people: motor neurons.  

By the same token, drugs that boost the role of HSPs in repairing damaged cells in other parts of the body don’t seem to work as well in motor neurons – the site of misfolded proteins in people living with ALS.   

With the help of her 2022 Discovery Grant, Dr. Vera Ugalde will look closely at why motor neurons are so bad at making HSPs, exploring an entirely new mechanism that could explain the problem. 

“Dr. Vera Ugalde’s research could pave the way for groundbreaking discoveries in motor neuron research,” says Dr. Viviane Poupon, President and CEO of Brain Canada.  

Her hope is that by finding out the exact reason HSPs work poorly in motor neurons – and why current drugs don’t seem to help – she can help open a new pathway for future therapeutics.   

“We have to do this” 

The project started when Dr. Vera Ugalde began speaking with her McGill colleague, long-time ALS researcher Dr. Heather Durham, who is also an expert on HSPs.  

The two realized quickly that Dr. Vera Ugalde’s technical expertise on protein homeostasis complemented Dr. Durham’s deep understanding of the pathways leading to cellular damage in ALS.  

When we started talking, we said, ‘we have to do this.’ It’s a good synergy.” 

Dr. Vera Ugalde

The ALS Canada-Brain Canada Discovery Grant Program has been made possible by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada), Brain Canada Foundation and ALS Canada.  

To find out more about the 2022 ALS Canada-Brain Canada Discovery Grants, read the full press release here.