UCalgary scientists examine our serial killers within

For as much as we know about what happens in the body at a cellular level, there is more we do not know. Dr. Chris Mody, MD, and Dr. Henry Ogbomo, PhD, members of the Snyder Institute for Chronic Diseases at the University of Calgary are seeking to explain how the body’s system of natural killer (NK) cells works, and why it stops working sometimes. NK cells are the body’s defence against cancerous tumours and microbes that can cause deadly infections.

“They kill tumour cells for a while, or they kill microbes for a while, and then they stop. We wanted to learn more about how the natural killer cells mount their attack,” says Mody, who is head of the Department of Microbiology, Immunology and Infectious Diseases, and a professor in the Department of Medicine at the Cumming School of Medicine (CSM). “We suspected that these cells used different tools, or at least used the same tools differently to fight infection as opposed to cancer.”

The researchers used a highly specialized, high-powered microscope to observe how human NK cells attack and destroy a cancerous tumour cell. They then compared that response to how NK cells attack and destroy a well-known fungus, Cryptococcus. Cryptococcus is a common infection and the leading cause of fatal meningitis in HIV-infected patients. It can also be a life-threatening infection in healthy individuals.

• Photo above: Henry Ogbomo, left, and Chris Mody have discovered that the body's army of natural killer cells have different ways to attack predators, like cancerous tumour cells and the microbes that cause infections. Photos by Pauline Zulueta, Cumming School of Medicine

“Our thought was if we could understand those cellular tools better, we might be able to help the body keep the natural killer cells turned on until the tumour is destroyed or an infection is overcome,” says Ogbomo, who is currently a medical student at CSM.

What they saw was remarkable. The NK cells have two distinct ways to attack these two predators in the body, cancer and Cryptococcus. To kill a cancer cell, the NK cell assembles all the killer molecules in one location and then blasts it at the tumour cell, like a bullet fired from a gun. For an infection, the NK cell assembles all the killer molecules in what looks like a string formation, almost like when a person swings a rope and spins in one spot. As the rope swings around it gathers the killer molecules for deployment. Their findings are published in Cell Reports.

“These cells are more powerful than we previously thought,” says Mody. “It’s as if they know this is a different enemy and therefore, just like an army, a different formation is needed in the attack.”

Mody says there is still more to learn about how to take advantage of this knowledge. The NK cells already know to be selective and not to attack healthy cells. Now, he says, we have to learn how to trick them into using all the tools at their disposal and to not switch off during an attack.

This research is supported by the Canadian Institutes for Health Research (CIHR), a postdoctoral fellowship from Alberta Innovates, and the Jessie Boden Lloyd Professorship in Immunology.

The University of Calgary is uniquely positioned to find solutions to key global challenges. Through the research strategy for Infections, Inflammation, and Chronic Diseases in the Changing Environment (IICD), top scientists lead multidisciplinary teams to understand and prevent the complex factors that threaten our health and economies.