Team receives new funding to advance understanding of misfolded proteins linked with dementia

While the world has been in the grip of COVID-19 for the better part of a year, it’s not the only pandemic that Canadians will pay an awful toll for.

This year, the Alzheimer Society of Canada estimates the dementia epidemic will affect more than half a million Canadians at a cost in excess of $12 billion.

With those numbers set to explode in the coming years, the federal government, through the Canada Foundation for Innovation, is investing $3.9 million in a $9.6-million infrastructure upgrade to support the University of Alberta’s leading protein folding disease research team.

“These diseases, which include chronic wasting disease (CWD) in deer and elk, used to be a black box, but we now know much more about the different risks for getting these diseases, and the different chemical steps as the diseases evolve to make the person, or the animals, sick,” said David Westaway, a professor in the Faculty of Medicine & Dentistry and director of the Centre for Prions and Protein Folding Diseases, who was a co-applicant on the grant, along with Michael Woodside, professor in the Department of Physics in the Faculty of Science.

At the heart of these neurodegenerative diseases are abnormal, misfolded proteins found in the outside membranes of our cells; these misfolded proteins are called prions and they attack brain cells.

“A protein in our cell is like a verb in a sentence,” said Westaway, who is also a member of the U of A’s Neuroscience and Mental Health Institute. “Proteins do useful things, they carry out actions, and those actions depend on them being in a specific shape; but if proteins get into the wrong shape, they will start performing malicious actions that damage our cells.”

In different types of dementia, Westaway said it looks like the common theme is that something goes wrong in a small area of the brain and then starts spreading outwards.

He said the reasons young people are protected from these neurodegenerative diseases—which include Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS)—are not fully understood. A generally accepted theory is that quality-control mechanisms that would normally keep our proteins in the right shape and right amount weaken as we age.

“Because of this weakening, these occasional proteins that end up in the wrong shape are not eliminated. They then start a domino effect to perturb other proteins,” he said.

The same protein misfolding effect is behind the recent unchecked spread of CWD in deer and elk populations; researchers now believe this always fatal disease now affects up 11 per cent of the deer populations in Alberta.

“That’s a crazy number,” said Westaway. “It’s a crisis in slow motion and it’s not going away.”

Unlike similar neurodegenerative diseases in humans, chronic wasting disease is contagious, although definite cases of spreading from animals to humans are not yet documented.

“An infected deer sheds particles, and these prion proteins can then transmit to the uninfected animal next to it. That animal then replicates the incoming particles and affects yet another animal. Before you know it, you have a train of transmission,” he said. “There is also an extra twist that is similar to the new, worrisome aspect of COVID-19 in that we are increasingly concerned about new variants of CWD prions that might be worse still.”

A related disease, bovine spongiform encephalopathy (BSE), better known as mad cow disease, certainly can transfer to humans through contaminated meat. This is what led to hundreds of cases of variant Creutzfeldt-Jakob disease in exposed European populations.

“Fortunately, there has been a lot of progress into these neurodegenerative diseases in the years since our last team CFI award in 2009,” Westway noted. “We’ve been really building on that.”

And while there has been progress, Westaway said the patient-ready interventions are still on the way.

“We’re trying to create good pipelines for new types of interventions to eventually hand off to third-party companies, be they established pharmaceutical companies or new startups. This will be needed to take these interventions to the next step,” he said. “We’re trying to pump this pipeline, and the net composition of our team is important to make this happen. The U of A is the centre of the hub, but the scope of our work includes collaborators at the University of Calgary and the University of Lethbridge.”

All told, five U of A-led projects received $24.1 million in CFI funding, of which $19.3 million is coming to the U of A. The balance will go to project partner institutions across Canada. An additional eight projects led out of partner institutions secured $8.2 million in CFI funding for the U of A. Proposals for matching provincial funding for these projects are with the provinces pending results.

CFI funding for projects led by U of A

Dennis Hall, Vladimir Michaelis

ELEMENTS: Earth, Life, Energy and Materials with multi-Elements for Nano to Terrestrial Structures

$5.1 million from CFI for project worth $12.7 million

Frank Hegmann, Jacob Burgess (University of Manitoba)

Ultrafast Nanoscale Quantum Dynamics (UltraNanoQD) Innovation

$3.9 million from CFI with $3.7 million coming to the U of A and $234,000 to U of M for project worth $9.7 million

Matthew Hicks, Liang Li

Canadian Analytics Network for Outcome Prediction In Exposures (CANOPIE)

$3.1 million from CFI with $2.6 million to the U of A and $591,000 to McGill for project worth $9.1 million

Ian Mann

RADiation Impacts on Climate and Atmospheric Loss Satellite (RADICALS) Mission

$8.1 million in CFI funding, with $6.1 million coming to the U of A and $2 million to the University of Calgary for project worth $20.3 million

David Westaway, Michael Woodside

Protein Misfolding Scientific Exploration (ProMiSE) Team: Infrastructure Support for Remediation of Protein Misfolding

$3.9 million in CFI funding for project worth $9.6 million

CFI funding where U of A is partner institution

Michel Fich (Waterloo), U of A principal investigator: Erik Roslolowsky

CCAT-prime: A Submillimetre Wavelength Survey Telescope in Chile

$4.9 million in CFI funding of which $750,000 is coming to the U of A. The total cost of the project is $28.8 million.

David Blowes (Waterloo), U of A principal investigator: Nicholas Beier

Toward Environmentally Responsible Resource Extraction: Developing Innovative Technologies for Predicting and Remediating Environmental Contamination

$3.3 million in CFI funding of which $203,017 is coming to the U of A. The total cost of the project is $8.5 million.

Mark Boulay (Carleton), U of A principal investigator: Aksel Hallin

Development of Next Generation Liquid Argon Dark Matter Detector and of an Underground Argon Storage Facility at SNOLAB

$6.9 million in CFI funding of which $3 million is coming to the U of A. The total cost of the project is $22.6 million.

Anick Berard (Université de Montréal), U of A principal investigator: Padma Kaul

Canadian Mother-Child Cohort Active Surveillance Initiative (CAMCCO)

$1.2 million in CFI funding of which $331,979 is coming to the U of A. The total cost of the project is $8.5 million.

Monica Emelko (Waterloo), U of A principal investigator: David Olefeldt

Canadian Consortium for Drinking Water Security and Climate Change Adaptation

$3.5 million in CFI funding of which $474,117 is coming to the U of A. The total cost of the project is $9.3 million. 

Gregg Adams (University of Saskatchewan), U of A principal investigator: Graham Plastow

Integrated genomics for sustainable animal agriculture and environmental stewardship (IntegrOmes)

$6.8 million in CFI funding of which $1 million is coming to the U of A. The total cost of the project is $15.9 million.

Bruce Gaulin (McMaster), U of A principal investigator: Larry Unsworth

Building a Future for Canadian Neutron Scattering

$14.3 million in CFI funding of which $400,000 is coming to the U of A. The total cost of the project is $47.3 million.

Paul Barclay (University of Calgary), U of A principal investigator: John Davis

A Quantum Diamond and Hybrid Photonics (QDHyP) Foundry

$5.2 million in CFI funding of which $2 million is coming to the U of A. The total cost of the project is $13.1 million. 

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