September 27, 2022
For this month’s member spotlight, we spoke with Michael Norris, a new faculty member in the department of biochemistry in the Temerty Faculty of Medicine at the University of Toronto. Michael joined U of T in April 2022 after completing a postdoctoral fellowship with Erica Ollmann Saphire at the Scripps Research Institute and the La Jolla Institute for Immunology in San Diego, California. Prior to that, the Mississauga native completed his PhD at U of T with Richard Hegele and Theo Moraes, also a fellow EPIC member, and his undergraduate and Master’s degrees at the University of Guelph. We’re excited to welcome Michael (back) to U of T and learn more about his work!
Can you describe your research?
My lab studies the structure and assembly of a group of viruses called paramyxoviruses. This family includes major human pathogens such as measles virus, which still infects over 7 million people every year, and Nipah virus, which kills 9 of 10 people infected. It also includes multiple livestock pathogens that cost the industry millions of dollars every year. We work on a key part of the paramyxovirus machinery, the matrix protein, which acts as a critical field marshal to gather and guide the assembly of viral components to build new viruses and release them from the infected cell. During my postdoc, I determined the high-resolution structures of several different paramyxovirus matrix proteins and learned how they hijack the human cell membrane to initiate the formation of new viruses. In my lab now, we use a variety of techniques, including X-ray crystallography and electron cryomicroscopy, to answer some of the crucial remaining questions about paramyxovirus assembly. For example, we still do not understand how matrix proteins interact with the other viral structural proteins at the sites of assembly. Ultimately, we aim to leverage this information to guide structure-based drug discovery for the design of broad-spectrum antivirals that inhibit the assembly process.
How did you become interested in virology?
For me, my interest in virology started in the third year of my undergraduate degree. I took a course called World of Viruses and during that class, I became completely captivated by viruses. I was amazed at how something so small with so few proteins could take over a cell entirely and cause disease. I thought this was just such a fascinating phenomenon and couldn’t wait to learn more. I think it was right then that I had that “Aha!” moment that this is what I want do for the rest of my life. I later went on to do my Master’s degree in the lab of the very professor that taught that course.
What’s the biggest challenge you face in your work?
Right now, it’s getting my lab set up. The COVID-19 pandemic has caused significant delays to the supply chain, so it’s been tough to get equipment and actually get things going. I will hopefully be in a place to really hit the ground running in October.
On the science side, being able to design inhibitors that target the viral assembly process is extremely difficult. A lot of this comes down to our lack of knowledge about the assembly process, as well as the lack of three-dimensional structures of matrix and other structural proteins. Having a three-dimensional structure is like having a blueprint. With it, we can begin to design compounds capable of binding to specific parts of the protein important for its function. We also lack high-throughput assays to measure the effectiveness of potential compounds on the assembly process. Without these biological assays, it’s quite challenging to identify which compounds to move forward in the discovery pipeline.
What excites you the most about EPIC?
To have a platform like EPIC that can bring researchers together and provide the infrastructure, resources and connections to advance infectious disease research, that’s huge. For a lot of us, maybe on paper it doesn’t look like we would have a lot of overlap but once we start talking, we start finding that there are a lot of areas where we can help each other. In Toronto, there are many researchers spread across several different institutions such that without something like EPIC, we may never cross paths with one another. It’s so valuable for us to be able to come together and see what other people are working on and say “Hey, we could collaborate on this. Let’s talk more about what you’re doing in your lab because I think it’s applicable for what I’m doing.”
EPIC also brings together researchers with extremely broad expertise. There are virologists, bacteriologists, immunologists, clinicians, biomedical engineers, computational biologists, epidemiologists, the list goes on. All of these researchers have different ways of thinking about and approaching problems. It is exciting to have a community of researches that can help you look at your problem in a way that may have never occurred to you before. It is these multidisciplinary approaches that truly lead to ground-breaking discoveries.
What do you hope to achieve through your research?
Paramyxoviruses are among the most infectious and deadly viruses known and have the potential to trigger a devastating pandemic. Despite the threats to public health and food supplies, we have no therapies available to manage or control outbreaks of severe disease caused by any paramyxovirus. Targeting the assembly machinery holds great promise because these matrix protein structures are highly conserved, meaning we could design an inhibitor for one virus that could potentially target all the other viruses in the family. By integrating structural and functional studies of these deadly viruses, I hope to not only improve our understanding of viral assembly, but also lay the foundation for the development of targeted, safe, and effective therapies capable of combating all paramyxoviruses, including those that may emerge in the future. One drug to target an entire viral family.
What advice would you give to young people who are interested in this area of research?
Find an area that excites you and follow that passion as far as you can. Pursuing a PhD and a postdoc are very challenging. It take years of hard work, dedication and the ability to withstand failure. When you’re excited and invested in your research, success becomes inevitable. I would also say don’t be afraid of failure. As researchers, many of our experiments do not work the first time. This often means you are trying something that has never been done before and you are pushing the boundaries of science. Learn from your failures and never give up. Lastly, I think it is very important to find patient and supportive mentors who really care about you as a person. This means supporting your mental health and career goals, and doing everything they can to help you get through the really hard times and achieve your goals.
What are you reading or listening to right now?
Right now, most of my time is spent reading and writing grants and biosafety manuals. There is a lot of paper work that goes into starting up a lab. Recently, however, I’ve started listening to a podcast called This Week in Virology. There are often great discussions about some of the exciting new virology studies coming out each week.