On defense: From varsity fencing to exploring the natural defenses of plants

Casey Chan is a Chemistry PhD student at Stanford and part of the Chemistry/Biology Interface (CBI) Training Program at Sarafan ChEM-H. CBI is an interdisciplinary training program that supplements traditional degree-granting PhD programs at Stanford. The program aims to help scientists speak multiple scientific languages spanning chemistry, biology, engineering, and medicine, and enable them to tackle the most challenging and important problems facing human health. Chan sat down to talk with us about her research towards developing safer pesticides and the lessons from her fencing career that she has applied to her work in the lab.

What research area do you work in, and what problem are you trying to solve?

My PhD research is looking at how insects and plants interact with each other on a molecular level. Since plants can’t move to escape the predators that eat them, like insects and other organisms, they have to make their own defenses. Plants have created a wealth of different chemicals that may be used as shields inside their bodies. Many of these molecules have never been synthesized in a lab before, and we don’t know a lot about them. I am looking at these defense chemicals that plants make and trying to see if we can turn them into something that is agriculturally useful, like safer pesticides.

There are also a lot of examples of pests that have become resistant to pesticides. The question is, can we use more natural formulations derived from plants to prevent specific pests from impacting crops? And, can we do this without harming beneficial pollinators or other animals that may contact crop plants?

Can you give an example of the molecular interactions between insects and plants?

In some cases, insects have developed their own strategies to override plant defenses and can eat plants that otherwise would be toxic. One example is the Colorado potato beetle. It eats potatoes and is a major pest. Potatoes produce molecules called α-solanine and α-chaconine to defend against such pests. These molecules work by binding to an enzyme called acetylcholinesterase. When consumed by insects, these molecules block the breakdown of acetylcholine, a neurotransmitter important in nerve signal transmission. Several current agricultural pesticides work the same way.

The concentrations of these molecules are really high when the potato is young and still green. This is why you shouldn’t eat green potatoes—the same molecules that are toxic to insects will make you sick, but they often decrease in concentration once the potatoes ripen and mature. But, Colorado potato beetles can consume  α-solanine and α-chaconine without dire consequences. They can overcome the natural potato defenses and eat the plants before the potatoes ripen.

Why can potato beetles eat green potatoes when we can’t?

Over evolutionary time, the acetylcholinesterase of the potato beetle has become less catalytically active and also has some mutations near its active site, related to insecticide resistance, that may make it less sensitive than other organisms to certain pesticides and plant acetylcholinesterase inhibitors, like chaconine. Through these and other mutations still being investigated, potato beetles have adapted to be able to eat any part of the potato at any stage of the life cycle without a problem, even when the potatoes are still green and full of chaconine.

By studying the differences in the catalytically important part of acetylcholinesterase across different insect species, I am trying to find plant molecules that will target just one flavor of acetylcholinesterase in specific insect pests, like the potato beetle. We want to be able to get rid of these pests with little to no effect on other insects, animals, or humans.

How did you get into this area of research and what attracted you to the CBI program?

During undergrad, I did inorganic chemistry research. But in graduate school, I wanted to combine chemistry with biological applications. This is what attracted me to CBI. I’m super thankful because without CBI, I wouldn’t have found my PhD advisor, Beth Sattely. She came to give one of the CBI lightning talks early on, and those talks allowed me to see the range of research happening at Stanford. Beth’s lab focuses on plant chemistry and how plants use different biosynthetic enzymes to make natural products. Transitioning to plant chemistry was really interesting to me—to see how plants are such great chemists and how we can utilize that to improve agricultural systems.

What is your favorite part of CBI and being part of ChEM-H?

There are so many good things! I’m really thankful for the additional mentorship from program managers Bria Castellano and Lynette Haberman. Through CBI, I’ve also met so many awesome friends. Through the talks and posters given through CBI, we’ve gotten to know what other people are working on and are always trying to find ways to help each other.

What do you like to do outside of the lab?

I am interested in science communication, and I really enjoy journalism. I’m also part of a science policy group, both here on campus and nationally, where we’re advocating for science research funding, as well as other science policy issues. Outside of that, I was a varsity fencer, but I’m recently retired, so I’m learning how to play basketball. That’s been super fun!

Do you find any connections between what you’ve learned doing fencing at a high level and how you think about science?

In fencing, the matches are fast, but improvement takes a long time. I was never good at attacking compared to defending, and it took about a decade to get to a place where I felt comfortable. Zooming out and thinking about my entire career, that was something that took patience. A PhD is similar. Just the repetition, showing up every day, and moving little-by-little will move you in the right direction. Fencing has been super helpful in making me realize that things like science don’t happen overnight. You have to put in the work, whether you get immediate results or not.

Elizabeth Sattely is an associate professor of chemical engineering in the School of Engineering. She is also a member of Bio-X and a faculty fellow at Sarafan ChEM-H.