Season 2, Ep. 1

Sophia Xu: The thing I like about plants is that they make so many cool natural products that are colorful, that are tasty, that smell good, and that really like enhance aspects of my life that I never really considered in the beginning.

[“Something Elated” begins]

Raleigh McElvery: Welcome to season 2 of “BioGenesis,” where we get to know a biologist, where they came from, and where they’re going next. I’m Raleigh McElvery from the MIT Department of Biology —

Conor Gearin: And I’m Conor Gearin from Whitehead Institute.

[“Something Elated” fades out]

McElvery: And together, we’re introducing you to the students behind the biology.

Gearin: Last season, we met three grad students who had encountered a surprise in their personal journeys or research projects. This season, we bring you stories of “Converging Paths.”

McElvery: We’ll introduce you to grad students who are melding seemingly disparate approaches in order to answer fundamental scientific questions our bodies and our world.

Gearin: Today we meet Sophia Xu, who’s bringing together modern scientific methods and ancient Eastern herbal remedies —

McElvery: Studying them in both fish and plants —

Gearin: To investigate how molecules in natural products interact with proteins in the human body.

McElvery: And maybe even find a cure for hangovers along the way. 

Xu: My name is Sophia Xu and I’m a fourth year PhD candidate in the MIT Biology program, and I work in the lab of Dr. Jing-Ke Weng in the Whitehead Institute.

[“Children of Lemuel” begins]

I grew up in Redmond, Washington, which most people know as Microsoft Town. And both my parents worked for Microsoft for several years when I was, well, when I was a kid. I guess the biggest influence was always my parents and particularly my mother. She has an advanced degree in math and was basically mine and my brother’s math tutor for our childhood.

[“Children of Lemuel” fades out]

So she and my dad are both immigrants from China. And they basically had to build their lives in the United States from nothing. And they were very much, like, wanted me and my brother to succeed and to live comfortable lives.

Gearin: Math wasn’t Sophia’s calling per se, but she saw the appeal of solving logic puzzles.

Xu: It was the beauty of these like elegant solutions that that got me going from one problem to the next. And so I started doing math competitions, and thanks to my mom’s tutelage, I ended up being OK at it and continued doing math competitions. Throughout high school, it was a fairly interesting experience because I ended up being basically the only woman on the team for a number of years. So that was an introduction into the world of STEM.

McElvery: But it wasn’t until high school that she finally found her niche, when she came face-to-face with her first research subject.

[“Rapids” begins]

Xu: I think it was junior year when I took AP Biology and we did this lab course where we looked at basically marine organisms that had been preserved in formalin. And I finally looked at this like fiddler crab sitting in this jar of formalin. When I looked at when I looked at the crab, I realized that basically everything that the crab does in order to keep itself alive and the things that its cells do and the things that we had learned in the class, they were also the things that my own body was doing to keep me alive, to keep me healthy, to keep me going. I guess I was at a stage of my life where I wanted to understand myself. And looking at this crab made me realize that by studying biology, I could learn more about myself.

Gearin: That summer, right before her senior year, she attended a 7-week research program for high school students at Stony Brook University. She was hoping to be placed in a psychology lab and explore the human experience. Instead, she ended up in a structural biology lab, studying mitochondria and gaining her first hands-on lab experience.

Xu: And I realized that like biology, the way that we had been learning it, like, taking a textbook, memorizing it from cover to cover, wasn’t really the way that biology really is. It’s very much about discovering what is unknown as opposed to memorizing what is already known. And then I just fell in love with like that question driven like, question-driven atmosphere and like the camaraderie of scientists working together towards a towards a common goal.

[“Rapids” ends]

McElvery: When it came time to select a college, it was a choice between the University of Washington, MIT, or Stanford. She chose Stanford.

Xu: And I was lucky enough that Stanford took me and was also very lucky that Stanford had a had a strong STEM program.

Gearin: Computer science was a popular major there, but –

Xu: It came down to not wanting to stare at a computer screen for a million hours a day.

McElvery: So, she picked biology instead.

Xu: Yeah, I bounced around between a couple of labs at Stanford.

[“Rafter” begins]

McElvery: First, there was Liang Feng’s structural biology lab.

Xu: He was working on the structural biology of membrane proteins.

McElvery: Then, corals in Steven Palombi’s lab.

Xu: We studied heat tolerance and corals and trying to understand how these coral reefs are tolerating different heating and cooling conditions .

McElvery: And finally, plant proteins with Wolf Frommer.

Xu: So he was building these fluorescent-based sensors to report on the intracellular concentrations of nutrients, like a variety of sugars, a variety of nitrogen-based nutrients. And I think really at that stage of my undergrad, I was interested in just seeing what was out there. So plants seemed exciting to me.

[“Rafter” fades out]

Gearin: I get that — they can taste good, smell good. They help produce the oxygen we breathe. They enhance quite a few aspects of our daily lives.

Xu: But plants, I guess, are seen as so very different from humans. Like they have these weird light responses. They eat sunlight. And studying plants, I guess is usually seen as like something that crop scientists do. But I think this is this is an unfair characterization of plants, because for basically all of human history, not only do we eat plants, we use plants to make the clothes on our back and the roofs over our head. We use them for medicine. And all of these like really great aspects of plants are driven by the specialized metabolism of plants.

McElvery: And Sophia had already experienced the medicinal properties of plants firsthand, back in high school when she went to visit her mom’s family in China.

[“When in the West” begins]

Xu: I accumulated an aggressive number of mosquito bites and some of them became very large blisters. So it was, like, my grandparents took care of me. And we also went to the doctor and through some combination of Western and Eastern medicine and probably my own natural immunity, I felt better eventually. I think it was it was really then that I started wanting to understand, like, what is it about traditional Eastern medicine that makes it work. Because there is thousands of years of literature of these medicines working for people and like some of them certainly don’t work. But some of them certainly do.

[“When in the West” ends]

McElvery: That experience in China stayed in the back of her mind as she considered graduate school.

Xu: I was at a stage where I thought I could do basically any science, really. The idea of like I had done some research in in undergrad, but that was very much like doing things that other people told me to do or asked me to do to further their own projects. And I wanted like the training to be able to develop my own questions and direct my own projects. And grad school was the natural next step for that.

McElvery: And, once again, MIT was on her list.

Gearin: This time, though, she decided to come.

[“Silver Lanyard” begins]

Xu: The distinguishing thing about MIT happened during the faculty dinner when I was able to talk to Steve Bell about something entirely not science-related.

McElvery: Steve Bell is one of the faculty members here at MIT Bio, and he was helping out with Interview Weekend.

Xu: We talked about a book series that we had both been reading: Red Rising. It’s essentially Hunger Games in space. And just like that, one small interaction just gave me the impression that in addition to caring about their science, the faculty also cared very much about that their students were well-rounded and had time to themselves and were interested in other things. And it was just like that small gesture that convinced me that MIT was the place for me.

[“Silver Lanyard” ends]

Gearin: As a first-year PhD student, she rotated in several labs. She was particularly excited for one rotation.

McElvery: Jing-Ke Weng’s lab at Whitehead Institute studies natural products made by a variety of organisms, but focuses on plants. Many of these plants come from ancient herbal remedy traditions.

Xu: There are a good deal of pharmaceuticals on the market in the modern day that are either derived from or related to natural products, and many of these are plant natural products. I think that taking the Western medicine scientific method to Eastern medicine and traditional medicine can help to bring together the understanding in both of those disciplines and really enhance the societal understanding and breadth of medicine.

Gearin: Jing-Ke’s lab studies how plants make these medicinal molecules, bringing together researchers from all sorts of disciplines. After her rotation, Sophia decided to stay.

[“Falaal” begins]

Xu: Yeah, so Jing-Ke does a really good job of hiring people with really diverse backgrounds to contribute to a common goal. So there are people who work with specific types of plants that are known to make molecules which are of potential interest to medicine. And they start from growing these plants, studying the transcriptomes, and like identifying candidate genes that could potentially be involved in synthesizing the molecules that they’re interested in. And then at multiple steps in this process, there are chemists who get involved. Computer scientists, biologists, plant biologists. And there are other people who take the same approach in fireflies or in bioluminescent jellyfish. And then there are still others — this is a relatively new direction in the lab — who take the molecules out of the plants and try to understand what they’re doing in humans.

[“Falaal” ends]

McElvery: How does Sophia fit in?

Xu: I consider myself a biochemist in training.

Gearin: She spends most of her time investigating one plant compound with medicinal applications

McElvery: The kudzu plant, which contains compounds that may have the potential to cure hangovers.

[“Building the Sled” begins]

Xu: The kudzu vine was originally imported to the United States from Japan. It was imported to stop soil erosion in the American South.

McElvery: You might know it as the weed that’s overgrown forests and houses.

Gearin: But it also has this history in traditional medicine.

Xu: Yes. So the kudzu vine is used to treat various aspects of alcoholism. So you don’t want to drink anymore. And the molecule that is responsible for this effect is identified and well-described. But then the flowers have this really interesting effect where they seem to be doing the opposite thing. They’re making hangovers less bad. So the idea here is to try to identify what molecule is made in the flowers that isn’t made in the roots that is mediating this effect.

McElvery: So basically, the two ends of the plant produce two opposite effects. Sophia wanted to understand why the flowers have this hangover-alleviating effect.

Gearin: And to make matters more complicated, she actually started off her plant project in fish.

McElvery: A postdoc in the lab had been using zebrafish to study the anti-anxiety effects of a different compound in the kava plant.

Xu: And the thought was that I could also use the zebrafish to study the effect of these kudzu flowers. There’s quite a bit of biology that is common to all forms of life. So if we want to understand how a molecule that we pull out of a kudzu vine or any plant can interact with human biology. it’s not widely accepted that we just give this molecule directly to humans. We need to test its safety in in a variety of other settings. And one of these is fish, which share a good amount of biology with humans. I was excited to learn new things. And just drink everything that grad school had to offer me, and if it was working with fish in a plant lab, then so be it.

[“Building the Sled” ends]

Gearin: Since her first year in the lab, Sophia has moved out of the zebrafish system, and is now working in test tubes, investigating how a group of molecules called isoflavones, isolated from the kudzu flower, interact with an enzyme found in humans.

Xu: the human protein that we’re working with is ALDH2.

McElvery: That’s Aldehyde dehydrogenase 2

Xu: So ALDH2 is the enzyme that’s responsible for clearing the hangover-causing molecule and is also the one that’s involved — that’s been implicated in Asian glow. Asian glow is the term to describe the flushing that many Asians get when they drink any amount of alcohol. And ALDH2 is… about one third of all East Asians carrying the reduced-activity mutation for ALDH2.

McElvery: At least one of the molecules from kudzu, called irisolidone, seems to boost the activity of ALD2, which makes the hangover go away faster.

Xu: And we’ve found that this molecule does seem to have a small effect in making this enzyme go faster in a test tube, which we interpret to potentially be at the base of alleviating hangovers.

Gearin: It’s a tantalizing clue. It suggests that an ancient herbal remedy could eventually be transformed into a modern hangover treatment.

Xu: I think for me, this project is more basic science driven, and trying to understand where are what are the atomic interactions between this plant-derived molecule and the human enzyme. But definitely when people ask me what I do at parties, I say that I’m developing a cure for hangovers.

McElvery: Beyond grad school, Sophia wants to continue exploring new fields.

Xu: I definitely know that I want to continue with the research side of things. Whether that’s in academia or in industry is still up in the air. I’m perhaps leaning more towards the academia side. But it remains to be seen.

[“Thannoid” begins]

Gearin: In the meantime, she has found time for fulfilling activities outside the lab.

Xu: What do I do for fun? I Dragon Boat. Dragon boating is a water sport. It is effectively canoeing, but with a really long canoe and it’s 20 paddlers, so 10 rows of two. And then there’s a drummer and a steers person. And on race day, we also put a dragon head and a tail.

McElvery: She also volunteers in Whitehead Institute’s educational programs for middle school and high school students, giving them hands-on opportunities to do science experiments.

Xu: I really enjoy the outreach programs because I get to interact with kids who are. you know, at an earlier stage of their lives and potentially you get to have some influence in showing them things that excite me. And maybe the things that excite me will excite them, too. When the kids ask questions, sometimes these questions are things that have never really occurred to me. It’s a lot of, like, why questions. And sometimes, the only answer I can give them is: I don’t know, but maybe someday you can answer that that question.

[“Thannoid” ends]

Gearin: Well, that’s all for today. Next time, tune in to hear about combing biology, chemistry and computer modeling to understand how proteins in our bodies interact.

[“Something Elated” begins]

McElvery: Subscribe to the podcast on Soundcloud and iTunes or find us on our websites at MIT Biology and Whitehead Institute.

Gearin: Thanks for listening.

[“Something Elated” fades out]

Produced by Raleigh McElvery and Conor Gearin.

Music for this episode came from the Free Music Archive and Blue Dot Sessions at www.sessions.blue. In order of appearance:

• “Something Elated” — Broke for Free
• “Children of Lemuel” — Blue Dot Sessions
• “Rapids” — Blue Dot Sessions
• “Rafter” — Blue Dot Sessions
• “When in the West” — Blue Dot Sessions
• “Silver Lanyard” — Blue Dot Sessions
• “Falaal” — Blue Dot Sessions
• “Building the Sled” — Blue Dot Sessions
• “Thannoid” — Blue Dot Sessions