Meet a Whitehead Postdoc: Mike Torrens-Spence

Mike Torrens-Spence is a postdoc in Whitehead Institute Member Jing-Ke Weng’s lab investigating how plants make molecules of medicinal and agricultural interest and how to recreate those molecules using synthetic biology. We sat down with Torrens-Spence to learn more about him and his experiences in and out of the lab.

What are you investigating?

In the Weng lab, we have a pretty broad focus on interesting or valuable chemicals coming from nature. Do scientists know how to synthesize a natural product of interest? If not, we can tackle this. We have a lot of these sorts of projects, where there is a valuable chemical coming from a plant, so we ask how the plant makes it and we try to recreate that biosynthetic pathway ourselves. A lot of these interesting chemicals occur in individual plant lineages, and the chemical biology is different from all the other plant species out there, because it's evolved somewhat recently. If you don’t know the biochemical pathway, you have to generate transcriptomes of all the genes that are actively transcribed in the plant, and look at the chemical structure of the natural product, and through knowledge of plant biochemistry you can infer the sorts of enzymes that are necessary to make the chemical. You then make a candidate list of possible enzymes and test them. Once you figure out the pathway, you can put the enzymes in E.coli or yeast so these hosts can make the chemical.

What’s an exciting project that you’ve completed in the Weng lab?

I've been in the lab for five years, so I've worked on a bunch of different projects. One interesting example is salidroside, which is a compound that comes from Rhodiola rosea, a small, fleshy plant that grows at high altitudes. People have been using it as a medication for a very long time; some think it's anti-altitude sickness, or good for mental health. You can buy it as a root or in a supplement at the grocery store. The plant grows really slowly and at high altitude, so harvesting it isn’t necessarily easy or sustainable. So we figured out how the plant makes salidroside, and recreated that in yeast and a species of tobacco plant. Jing-Ke has used this pipeline several times to produce chemicals from nature in yeast, E. coli, and plant systems. I’d say we’re at the prototype stage, but the hope is that downstream you could eventually go to industry and have them use our systems to mass produce these chemicals of interest quickly and sustainably.

More recently, we figured out how plants make salicylic acid, which is a critical plant defense hormone. When a plant is invaded by pathogens or another biological stressor, this chemical is produced and signals the plant to defend itself. We recently figured out the common pathway for this compound in all plants, and then figured out that there's an extra step in a certain mustard family of plants, like Arabidopsis, the common model organism. This has a lot of agricultural applications; if you can make super pathogen-resistant plants, that is very valuable.

How did you end up at Whitehead Institute?

I was born in New Mexico, and grew up in Virginia. I went to Virginia Tech as an undergrad, and then stayed in Blacksburg, where Virginia Tech is, and worked for a startup company as a research associate for two years. That was a weird experience because a few weeks after I was hired the company fired about half of the employees. I was retained even though I was one of the newer people, but I didn’t have a lot to do for the first six months. At the same time, I was taking graduate classes for fun at Virginia Tech, and that basically segued into a PhD. I didn’t apply normally, I just kind of slipped in there. I worked in a vector-borne disease lab that studied mosquitoes that spread disease, but somehow, I ended up with a research project studying plant biochemistry. My PI was studying this family of enzymes that are responsible for making the cuticle in insects, but also produces super interesting molecules in plants, like molecules with medical applications. So I started learning about specialized metabolism in plants, and that’s how I came across Jing-Ke’s work. His research interests and mine were pretty similar, so I shot him an email about a postdoctoral position. I joined his lab early, maybe six months after he started it, and I’ve been here for more than five years now. It’s been a good fit.

What are your hobbies?

I do a lot of sports, mostly group fitness classes at this point. I run a lot, and I box. Swimming, rock climbing, skiing; I think sports are good stress management. Boxing especially is fantastic. I got scooped a few years ago, when I was doing a lot of boxing, and hitting a heavy bag was very therapeutic.

Traveling is another thing that I like to do. My family has a shared document tallying the number of countries we've been to. Most of my family members have country counts in the seventies or so. I'm in the low thirties, which is pretty good, but I'm still losing miserably compared with my immediate family members. It’s not fair, though, because one of my sisters works for the state department, and my other sister lives in Paris, which is really convenient for traveling. My parents retired and now travel a lot, basically four weeks on, four weeks off. I think my parents' objective in retirement is to beat my sisters in competitive traveling.

Do you have any pets?

My wife and I have a cat, Coco, and I photoshop the cat into weird photos that I think are pretty amazing. It was actually my sister’s cat. She adopted it from my parents’ neighbors when she was living at home, and then promptly left so my parents got the cat. When they retired, since they are always traveling, they gave us the cat—whom I’ve become very fond of.

What did you want to be as a kid?

Probably some sweet dragon monster, karate master something or other. Maybe that is how I got into biochemistry: I wanted to one day mutate myself into some kind of dragon monster that knew kung fu and had a lightning sword, very specifically.

What’s the coolest thing you’ve seen in the lab?

A lot of things in science are black boxes. You get your one output, which is a peak in a chromatogram or some sort of signal, and then you infer what biologically is happening because you can't actually visualize it. So I think anything that you can actually view is super satisfying. We make a lot of chemicals in the lab, and we work with a few things that are bioluminescent, florescent, or chromophores, so they have a color. Those projects are great because you can try to build the pathway in yeast and if your cultures turn yellow or purple, you know your biosynthetic hypothesis was correct without having to grind up that yeast and send it to the metabolomic core for analysis. You can just see that it’s producing the compound you want. Color is also a good way to screen for specific types of enzyme activity, and the immediate visual feedback is just very satisfying.

I'm working on a protein crystal structure at the moment—figuring out an enzyme’s three-dimensional shape—and it's so fun. You get to this point where you know you've got the data and you've got a partial solution, so you know the answer's there and you're going to solve it with some work. In this process you become super familiar with the protein. You stare at your model of it on the computer for hours, just clicking on it, moving it around trying to fit it to the experimental data. You close your eyes at night and you see the electron density and can start to imagine catalytic mechanisms. You also see weird abstract stuff in there. I sent a picture out to the lab Slack account recently to ask whether something in the electron density map looked more like a horse or a dog. The consensus was an afghan hound.

How do you deal with the inevitable failures that one experiences doing research?

 What worked for me is starting my postdoc off with ten projects. That means a long lead time, so maybe if you're trying to get a paper out in the first year or two, it's not a good way to do it. But if you want to guarantee that you'll be publishing in the long run, and if you can afford to be a postdoc for more than two years, then I think having a bunch of projects to start with is a good strategy. Maybe three quarters of them end in failure at various steps along the way, but for the final quarter you can gather enough data together into a cohesive story to make a paper.

Where do you see yourself in ten years?

I’m currently applying to faculty jobs, so hopefully, I’ll have tenure somewhere in ten years. It’s hard to say, because I don't think you can really picture these things until you're there.

But this field, learning about how chemicals in nature are made and developing useful natural products, is a fun place to be right now. We recently got the tools to crack these problems, and there aren't that many people doing it yet. Where do I want to be in ten years? I don't want to be a professor with my head in the clouds. I want to try to do something that benefits people in the next decade, not a hundred years from now.