老司机直播

How does COVID-19 invade our bodies so easily? 老司机直播 researchers use 'organ-on-a-chip' model to find out

Milica Radisic
Milica Radisic, a professor in 老司机直播's Faculty of Applied Science & Engineering, is working with Axel Guenther and Edmond Young to create tiny models of the nose, mouth, eyes and lungs to better understand how COVID-19 infects organs (photo by Neil Ta)

In order for a COVID-19 vaccine and antiviral drugs to be developed, scientists first need to understand why this virus spreads so easily and quickly, and why it invades our bodies with seemingly little resistance from our immune system. 

To understand how COVID-19 enters the body and does its damage, a team of top researchers from universities, hospitals and the National Research Council of Canada (NRC) at the Centre for Research and Application in Fluidic Technologies, or CRAFT (a collaborative centre between the University of Toronto and the NRC), are adapting an approach developed by 老司机直播鈥檚 Milica Radisic, Axel Guenther and Edmond Young to create miniscule models of the nose, mouth, eyes and lungs.

The focus will be on understanding why this virus is so effective at breaking through the body鈥檚 natural defenders against viral and bacterial invaders, otherwise known as epithelial barriers. These barriers 鈥 created by epithelial cells that pack themselves tightly together 鈥 are present throughout our bodies. 

鈥淣ormally, these epithelial barriers do a good job of helping us fight infections,鈥 says Radisic, who is a professor in the department of chemical engineering and applied chemistry in the Faculty of Applied Science & Engineering.

鈥淏ut this virus has found a way to invade the barriers. That鈥檚 our focus 鈥 why is this?鈥

In recent years, Radisic鈥檚 research has allowed her to make important progress in developing models of the heart on computer chips. The hearts 鈥 made from human cells 鈥 capture the key functions of an actual heart. That research, in turn, has been extremely effective in regenerating heart cells. Radisic has also used this organ-on-a-chip model to study how nanoparticles from air pollution damage our organs. 

Now, by creating mini-models of other human organs,the researchers can take a detailed view of just how COVID-19 is working. 

鈥淭his method allows us to study the problem without having to touch a human and potentially harm someone,鈥 says Radisic, who is also Canada Research Chair in Functional Cardiovascular Tissue Engineering. 

鈥淭hat鈥檚 the beauty of it. We can do our research early in the viral infection. You can鈥檛 do that with a human, because once you know you have COVID-19, you鈥檝e been infected for two weeks. With organ-on-a-chip, we can study what happens within 24 hours of COVID-19 entering the body.鈥 

A big part of the challenge with COVID-19 is that it鈥檚 new and no one is immune.      

鈥淭here isn鈥檛 anyone who has developed the T and B cells that are part of what we call 鈥榓daptive immunity鈥 鈥 the cells you build up as you are exposed to diseases. We are all born with innate immunity. This works early when we are invaded with a virus. It finds things that don鈥檛 belong in your body and tries to clean it up.鈥 

Radisic says having a lung-on-a-chip will enable the team to study the innate early response of the immune system to COVID-19. 

Once the models are built with commercially available cell lines to set the groundwork, the human cells for the organs-on-a-chip will be supplied by CRAFT members Tereza Martinu (respirology) and Ana Konvalinka (nephrology) of University Health Network and 老司机直播鈥檚 Faculty of Medicine. The live virus will be acquired from Karen Mossman, a researcher in pathology and molecular medicine at McMaster University. Mossman was involved in isolating the virus with 老司机直播 scientists Samira Mubareka and Robert Kozak, who are based at Sunnybrook Health Sciences Centre. 

鈥淜aren has the live virus, so we will give her the chips and she will infect the organs in a special level three facility,鈥 Radisic says.

Other CRAFT team researchers include Teodor Veres and his colleagues Daniel Brassard, Lidija Malic and Sue Twine from the NRC; Guenther and Young, both of 老司机直播鈥檚 Faculty of Applied Science & Engineering; and Wolfgang Kuebler of the Keenan Research Centre for Biomedical Science, St. Michael鈥檚 Hospital and surgery and physiology at 老司机直播. 

The group will also experiment with the 鈥淧owerblade,鈥 a technology the NRC in Montreal is using to test the blood of astronauts while on space missions. It will be repurposed by the research team to examine its potential for testing people with COVID-19 when they arrive at a hospital.

鈥淥nce we figure out which molecules are biomarkers for a severe case of COVID-19, the Powerblade will be able to read that at point-of-care,鈥 Radisic says.

鈥淭he health-care providers will then know how your innate immunity is reacting and if the virus will be severe or not. The problem with COVID-19 is that it works fast. You look good one minute and then, suddenly, you can be in real trouble. So getting earlier markers is important.鈥

Read about the action fund 老司机直播 launched to support high-impact COVID-19 research

UTC/Freelance