“We’re made up of molecules. We’re looking at what it is about them that makes them special: what it is about them that makes them work when they work properly, and what it is about them that makes them malfunction in the course of, say, disease.”
Biophysicist Lewis Kay, professor of molecular genetics and biochemistry at the University of Toronto, works to understand health and disease at a molecular level. And to do this he needs to understand how molecules interact with each other and evolve over time, because our molecules are anything but static.
“Just like if I take a picture of somebody, I get a static entity: I learn something about that person — what they look like, how big they are, perhaps — but I don’t learn a lot about them,” explains Kay.
Going beyond a snapshot to something more like a video requires Kay to develop new technology. His go-to experiment uses a method called nuclear magnetic resonance (NMR) spectroscopy. To better conceptualize how it works, Kay likens molecules to collections of bar magnets.
Just like life-sized bar magnets, which each have a north and a south pole, molecules can be arranged in ways that place north poles with north poles, or south poles with south poles — but because like poles repel each other, this is a high-energy configuration. Conversely, north poles being next to south poles represent low-energy configurations.
In an NMR experiment, forces are applied that raise the energy in the system to bring like poles together. Pushed into a high-energy configuration, Kay then monitors the system to see how the applied forces impact molecules as they return to their lowest energy states.
“I really have to learn about the nuances of these molecules. And to do that we have to develop the technology which not only allows us to have a picture of these molecules, but to understand how they evolve in time in response to various stimuli,” adds Kay.
Depending on the disease, some molecules need a boost, and others are already too active. By understanding each molecule and its interactions, Kay hopes to pinpoint whether their functionality needs to be turned up or down to restore health. He also develops tools that may help manipulate molecules to achieve the effect that a patient needs.
“We’ve got to be able to understand these biological molecules at a very fundamental level if we really want to address practical questions that come from disease,” says Kay.
“Molecules are at the root, and we want to be able to understand these molecules fundamentally. So that’s my North Star, that’s where we want to be now, that’s where we’re going to be working towards in the future.”
