In conversation with Dr. Lewis E. Kay, winner of the Canada Gairdner International Award

In advance of tonight's Gairdner National Program Lecture, Dr. Lewis E. Kay talks to the Reporter about nuclear magnetic resonance, the p97 molecule and what it means to win the "baby Nobel."
Dr. Lewis E. Kay, Professor in the Department of Biochemistry at the University of Toronto, won the Canada Gairdner International Award in October.

By Meaghan Thurston

Dr. Lewis E. Kay, Professor in the Department of Biochemistry at the University of Toronto, was recently awarded Canada’s highest prize for biomedical research, the Canada Gairdner International Award, for his work on the development and use of nuclear magnetic resonance (NMR) techniques for investigating molecular motion and short-lived conformations in large multiprotein complexes. Professor Justin E. Nodwell, Chair of the Department of Biochemistry at U of T, characterized Dr. Kay’s contributions as, “seeing the unseeable.” Professor Kay will deliver the Gairdner National Program Lecture tonight, November 14, at McGill. Register to attend.

On Oct. 27, how did it feel to receive the Canada Gairdner International Award, which many people in the science research community call the “Baby Nobel”?

Now that I have had some time to reflect, I have gained an even greater appreciation for what it means to be recognized by the Gairdner Foundation. The week of the Gala was just fantastic. I had the opportunity to visit my alma mater, the University of Alberta, and then to return home to Toronto, where I have been a professor for 26 years to receive the award. As far as my experience is concerned, I cannot imagine any award celebration reaching that level of impact. I am extremely proud of the science, and it was emotionally meaningful to be in the presence so many outstanding researchers, my family and friends, and in my city. Though there are many as deserving or more deserving than I in Canada, I am the first to win this award since McGill’s Nahum Sonenberg in 2008. My hope is that Canadians will continue to achieve the deserved recognition for their excellent science through awards such as this in years to come.

Tell us about the title of your upcoming talk, Nuclear magnetic resonance, Why bother? Studies of the p97 molecular machine provide an answer.

Many of the molecules in our cells are like very large machines that are responsible for biological function. Like the machines that power a car, microscopic machines work through movement, synchronicity and change in response to other components. In other words, these molecules do not exist in isolation, but are involved in interactions with other molecular players. In my field, the difficulty was improving technology to be able to have a closer look at the large molecular machines that are the focus of my work. It is very challenging in general to view these molecular machines, but particularly in nuclear magnetic resonance spectroscopy of proteins (NMR), which obtains information about the structure and dynamics of proteins.

In recent years, we have developed experiments that allow us to look at these molecular machines and ask questions about their dynamics. Much effort has been focused on getting a picture of the three dimensional structure of molecules, but much less emphasis has been placed on understanding how the picture changes with time and in health and disease. In my talk at McGill, I will illustrate that how the picture changes in disease states, specifically involving a very important molecule called p97, is worthy of attention. My title question is of course a rhetorical one. Exciting technological advances and other techniques have questioned the validity of the approach I take in my research, but I can provide an important response to that challenge.

How does p97 impact the body in disease?

p97 is a very important molecule that maintains cellular levels of protein. In the body, you have the movers and shakers that carry out the enzynamic reactions that are involved in maintaining functional molecules. p97, however, is multi-functional: they transport molecules to cellular garbage cans; they are involved in the repair of the genetic blueprint, i.e. DNA, from damage; they are involved in regulating molecules that in turn give cells their shape and form. p97 is a regulating molecule. When you have mutations in p97, you get aberrant function and advanced disease. It is implicated in cancer and in neurodegenerative disease, the latter of which I will discuss at McGill. I will be talking about a series of disease mutants and about the methodologies that allowed us to ask novel questions about this particular system.

You compare proteins to “machines.” Why is this metaphor useful when talking about the molecular functions of proteins?

When speaking about the work that I do, the language can very quickly become technical and mathematical; however, I believe it is important for me to express what it is that I do to people who are not experts in my field but who pay for my work through public funds, including through provincial and federal research grants.

As we age, everyone will face health issues, and it seems to me that we should be spending more of our time and effort to make the government realize the importance of investing in basic research. The fact of the matter is that basic science is not funded at the level it should be in Canada. We live in an era where people live longer and these extended lifespans generate all sorts of new diseases that have very significant implications for our society. We are also in an era where scientific advances are more rapid than ever before. At this critical juncture in time, we must invest more enthusiastically in basic science; however, we do not need exorbitant amounts of money to have a significant effect on science and health. While many scientists are increasingly pushed toward the area of ‘translational research,’ the one thing I want to emphasize is that you cannot translate impact without first doing the fundamental research. It is perhaps important to point out that this interview has been transcribed using a computer and is probably being read online – technologies that are a product of fundamental physics and quantum mechanics. Neither would have happened if we were solely focused on putting out a product rather than doing fundamental research.

When I give a talk, I endeavour to make my work accessible and appealing, hoping to spark interest and curiosity, which are the two main ingredients that drive discoveries and change in the way we interact with the world.

2017 Gairdner National Program Lecture;  Nuclear magnetic resonance, why bother? Studies of the p97 molecular machine provide an answer.

Nov. 14, 5 p.m., McGill Faculty Club, 3rd Floor, Billiard Room. Register online.