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The ongoing work of two infectious disease researchers at the at ����ɫ�� is setting the stage for future collaborations and discoveries around COVID-19.

Both researchers—Drs. Jennifer Corcoran and Braedon McDonald—whose independent work led to important advancements in our understanding of the virus, are receiving grants from the Canadian Foundation for Innovation (CFI) to better equip their labs. This newly specialized equipment, funded by the CFI’s John R. Evans Leaders Fund (JELF), will help ensure the Snyder Institute for Chronic Diseases remains a leader in the field of pandemic-related research.

Named for the first chair of the CFI board, JELF awards up to 40 per cent of a project’s funding requirements in an effort to help “excellent researchers” by providing the foundational research infrastructure they need to lead in their respective fields and produce transformative work.

Demystifying infections in the ICU

For the longest time, Dr. Braedon McDonald’s work as an intensive care unit (ICU) physician remained a well-known yet poorly understood aspect of hospital medicine. But all of that changed as the pandemic started to take hold.

“Issues in the intensive care unit have been thrust into the public eye in a big way in the last year,” he explains. “Before the pandemic it was a world not many people had to think about.”

McDonald says the exposure helped sensitize people to the realities of the ICU, from the dire circumstances of patients to the challenges facing the staff who work around the clock to provide care. One of the biggest issues they face is infections.

“When our defences are down, like they are for patients in the ICU, the bacteria that normally exist in balance in our bodies take advantage of the opportunity to multiply and thrive,” he says. “This can result in a life-threatening infectious syndrome called sepsis or an infection caused by antibiotic-resistant super bugs.”

Seeing this in abundance throughout the pandemic, McDonald focused the work of his lab on discovering why ICU patients are so susceptible to these problems. He paid particular attention to the role played by the microbiome, the vast collection of micro-organisms that exist within our bodies.

“My research program is built to span the realm of bench-to-bedside in order to not only make discoveries to understand why this is happening but to translate that into meaningful ways to help patients suffering from these conditions in the ICU,” says McDonald. “The CFI grant gives us the opportunity to build a one-of-a-kind laboratory to study this problem while forging new collaborations with microbiome researchers across the university.”

The hope is to speed the process of discovery in order to help more patients recover from these devastating infections. Not only is the problem of scientific interest; he says there is also a true clinical urgency to find a solution.

The first step towards understanding

When COVID-19 started to sweep across the globe, most people wanted to stay as far away from the virus as was humanly possible. Virologists like Dr. Jennifer Corcoran, however, couldn’t wait to get their (gloved, protected) hands on it.

“From a science perspective it was exciting,” she says of her work in ����ɫ�� Containment Level 3 lab. “I was happy to be able to contribute and do something to further the world’s understanding of this virus.”

Corcoran’s research dives deep down to the very basic, cellular level of interaction between viruses and human cells. In particular, she is interested in learning how certain viruses trigger a wave of inflammation that can spin out of control.

For more than a decade, her work focused on Kaposi's sarcoma-associated herpesvirus (KSHV), a cancer-causing virus that’s a close relative of Epstein-Barr virus. Throughout the pandemic, however, she turned her attention to COVID and its tendency to wreak inflammatory havoc on its victims.

Corcoran discovered that processing bodies—one of several checkpoints in our cells designed to keep our inflammatory responses measured and in control—fall apart when cells are infected with the virus that causes COVID-19. You can think of these processing bodies like bouncers at a Shawn Mendes concert. Without them, throngs of screaming fans would soon take over, leaving Shawn defenceless on the stage.

“We’re proposing that processing body loss is one of several factors that contribute to increased inflammation in severe COVID,” she says. Corcoran also clarified that at this time, these discoveries were made in infected cells in a lab, and have not yet been made in patients. However, the significance remains the same. “When you think of how viruses attack our bodies and how they manipulate our cells to do what they want, this could be one way that inflammation gets out of control.”

Corcoran initiated her research program on viruses and processing bodies at Dalhousie University in Halifax before moving to Calgary with her family. Since relocating to Calgary, she’s been continuing her work using borrowed equipment from other labs. She says with the CFI-JELF grant she can outfit her lab with specialized equipment to help her analyze and visualize what’s happening in cells.

“It’s really great to be supported in this way,” she says. “I’m thrilled!”

While it may be years before Corcoran’s discoveries lead to changes in patient care, she says work like hers is a vitally important first step towards understanding how viruses operate in the human body.

“Viruses are the best cell biologists because they are so adept at taking our cells apart and rewiring them to their own benefit. By better understanding how a virus works to manipulate our bodies, we can better understand how to fight it. And discovery work like ours is the first step.