Mar 26, 2015

Breaking Down the Molecular Dance of Life

Research
Proteasome
By

Erin Howe

Basic science research is often the first link in the chain of discovery, uncovering new knowledge and setting the stage for further investigation. It’s these important initial steps that Lewis Kay is passionate about.

Professor Lewis Kay

“You take something that seems to be fairly esoteric and you can turn it into something that is incredibly useful,” says Kay, a Professor in the departments of Biochemistry, Molecular Genetics and Chemistry.

Kay is a leader in the field of nuclear magnetic resonance (NMR) spectroscopy, a technique used to determine a compound’s structure. A compound is a molecule with at least two different elements — like water, which has two hydrogen atoms and one oxygen atom.

Kay explains many molecules are made up protons, which are like tiny bar magnets that give off small magnetic fields that can be detected using a spectrometer. The protons leave signatures and Kay and his lab find ways to decipher them and uncover more information about the molecule’s structure and dynamics.

“Our research involves developing new experiments to do funky things to these ‘bar magnets’ in ways that allow them to reveal their innermost secrets to us,” says Kay.

NMR, the technique used to uncover these secrets, involves putting the molecules into a magnetic field to orient their bar magnets in particular ways. The bar magnets are energized, and their response is interpreted in the context of the molecular properties the lab is investigating. The spectrometer gives researchers an idea of what the molecular systems look like over time.

“Just like a person’s portrait can’t tell you everything about them, the information revealed by the structure of a molecule doesn’t reveal the whole picture, either,” explains Kay. “A photo might capture that person in the moment it was taken, but it doesn’t tell you how they respond to stress, if they are happy or sad, or how quickly their moods change. Similarly, to understand how a molecule functions, you need to know its prescribed structure, which may change in response to various stimuli. We want to understand those various structural changes and how they influence a molecule’s function.” 

Some of the questions Kay’s team helps answer involve the “molecular dance of life” — the ways biological molecules like proteins recognize and interact with one another. Through the discovery of new ways to understanding this ‘dance’, Kay and his team lay groundwork for future study into how to manipulate the interactions and eventually, improve human health.

For example, some molecules are known to bind together when they are performing properly. Others might bind together when they stop functioning.  Knowing about the mechanisms that prompt such changes can provide insight into how to prevent the deviations that lead to disease.

One system Kay’s lab explores is the proteasome, which is like a garbage can our cells use.  The proteasome chops up damaged or old proteins in our cells. In some illnesses, changing the speed of this process can impact disease progression. For example, cancer cells metabolize quickly, if you can slow down the proteasome, you can selectively destroy cancer cells. The Kay lab studies the way these ‘garbage can’ proteasomes change shape and communicate. By doing this, the team can look at various potential drugs and how they might work.

Proteasome

Kay’s passion is for doing the best science he can — and for him, that means taking a hands-on approach to research.  One way he does this is by writing the computer code used by the lab’s machinery.

“I am motivated by doing the experiments with my own hands,” he says. “As a principal investigator, there are certain areas I’m excited to remain involved in, like writing code, doing physics and hopefully translating ideas into reality and applying them to a system or two in our lab. It’s amazing to share our work and know others can benefit in ways that I could never imagine.”

The lab shares its methods freely with anyone who asks for them and researchers around the world benefit. Many hundreds of scientists in academia and industry use the methods Kay and his team develop.