Q&A: Lindsey Macpherson, UTSA Brain Health Consortium

Macpherson combines her love for cooking in her research on the sense of taste, sometimes even cooking in the lab.

(April 17, 2018) -- Lindsey Macpherson is an assistant professor of biology at The University of Texas at San Antonio specializing in sensory neuroscience. She and her students are currently researching the sense of taste and the molecules, cells and circuits involved in communication between the tongue, stomach and brain.

Macpherson joined UTSA in 2017 as part of the university’s formation of the Brain Health Consortium, a world-class research cluster dedicated to developing groundbreaking approaches for treating brain diseases and injuries. She joined UTSA from Columbia University, where she completed her post-doctoral fellowship, and The Scripps Research Institute, where she completed her doctoral studies.

How would you describe your current research? Why did you decide to focus on this topic?

I'm interested in sensory neuroscience, especially chemosensation, which is our ability to detect chemicals in the environment. Taste and smell are the senses that usually come to mind when you think about chemosensation, but chemicals are also sensed by nerves innervating the skin as well as the airways and digestive tract.

The research in my laboratory focuses on the molecules, cells and circuits of chemosensory systems starting with the detection of a chemical stimulus by a molecular receptor, to perception of that stimulus by the activation of neural cells within a circuit, which leads to a behavior or reaction to that stimulus.

I find this topic to be so fascinating because we experience the world through our senses. Our day-to-day experience is limited by the types of receptors our cells express and the connections between neurons in our brains that produce the representation of the world around us.

I'm excited to do research in this field because so many basic questions remain about how we detect and process sensory information. Years of evolution have produced highly sensitive and sophisticated systems to inform us if a potential food is nutritious or toxic. My job as a researcher is to determine how that works. My approach is similar to that of a mechanic-in-training: get a flashlight, observe what's going on, tinker with it, remove or modify a piece and see what happens to the machine, and eventually use what I've learned to predict the function and connections between each piece.

What is one experience as a professor or researcher that has inspired you?

Going into graduate school, my goal was to finish my Ph.D. and then return to the biotechnology and pharmaceutical industry where I had some experience working as a technician. This plan was thrown out the window after I rotated in Ardem Patapoutian's laboratory at The Scripps Research Institute in my first year.

At the time, we were studying temperature-sensitive ion channels. One of these channels could be activated by painfully cold temperatures but also by pungent chemicals such as those found in wasabi and cinnamon. My rotation project was to identify other compounds that could activate the channel. Since cooking is a big hobby of mine, I gravitated toward garlic and onions, thinking about the painful burning prickling sensations you get on your lips and tongue when you eat them raw.

Every morning, I would stink up the lab preparing my garlic and onion extracts to assay their effect on the channels. Imagine my excitement when I looked through the lens of the microscope, and saw the cells expressing this channel light up bright as Christmas trees in response to the garlic extract!

The question was then, “What is the active component in these complex extracts that is acting as the ligand for the receptor?” Again, thinking of my cooking experience, I noted that roasted garlic and cooked onions don't have the pungency of the raw vegetables; perhaps I could use this insight to find the active compound. Indeed, extracts of cooked garlic no longer activated the channel, and with the help of our collaborators in the chemistry department, we were able to pin down the main active compound as allicin, a chemical that is produced by an enzyme when raw garlic or onions are cut or crushed. Baking the vegetables inactivates the enzyme, so that allicin can no longer be produced. So next time you feel the pungency of garlic or onions, think about allicin binding to TRPA1 channels activating the pain-sensing neurons innervating your mouth.

This experience sucked me into the field of basic academic research. I got such a thrill from trying something completely new, making hypotheses and testing them. Throughout my Ph.D. and postdoctoral work, and now as an assistant professor, I'm continually inspired by interactions and collaborations with other scientists. Science at its best is a team effort.

What’s one token of advice you would give your younger self?

I've always been a schemer. I love making plans, from to-do lists to vacations to life goals. That's often a good thing, but I would tell my younger self to be more open to opportunities as they arise and not to worry so much that this might deviate from my original plan. Looking back, these opportunities were usually positive and I needlessly worried that I was going off-track.

What advice do you have for a student considering joining your field?

Don't be too hard on yourself. You have to be very tolerant of failure. I tell all the students who come to the lab to do research that they need to expect failure 99 percent of the time. If research was easy, we would have figured everything out already! The key is to learn from failure, don't keep banging your head against the same wall, move one step in another direction, informed by the previous failure, and then try again.

What is the most important thing going on in your field that no one is talking about?

I don't think it's a secret that it's a really exciting time for biological research and especially neuroscience. Technological advances like CRISPR gene editing, optogenetics, single-cell RNA sequencing and computational modeling are making a huge impact by accelerating the speed of research and introducing completely new ways to tackle our research questions.

Do you have a favorite quote?

"We’re filled with passion for science, and passion is the quality that leads one to ignore consequences. (And that’s where babies come from.)"
- Adam Ruben, science writer and humorist

— Joanna Carver

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