Solving Complex Puzzles in the Lab and in Life

By Julia Van Develder

In 1665, British scientist Robert Hooke was the first to observe what we now know to be the basic structural and functional unit of all living things—the cell. It would be almost two centuries before scientists recorded the next groundbreaking discoveries in cell biology—that all plants are composed of cells, that all animals are composed of cells, and that all cells come from preexisting cells.

In the century and a half since those discoveries, our knowledge about cellular structure and function has increased exponentially. But we’re still a long way from having a solid under-standing of how cells actually work.

Associate Professor of Chemistry Teresa Garrett’s research is focused on one class of molecules that plays a key role in the cell—phospholipids. “They comprise the cell membrane in all living organisms,” says Garrett. “If you think of an orange as a cell, the phospholipids are like the skin of the orange. They actually define a cell, and they regulate what gets in and what gets out. So you can think of them as sort of the gatekeepers.”

A member of the Vassar faculty since 2007, Garrett teaches courses in general chemistry, biochemistry, and protein chemistry, and runs an active lipid research program that involves student researchers. “There are six degrees of separation between what I do and some potential good that could come of it in practice,” says Garrett. “Basically, with regard to a certain class of lipids called headgroup acylated phospholipids, I want to understand how they are made and what they do.

How do these machines actually work? It’s almost like a kid taking apart a toaster to see how it works.”

Growing up, I was always kind of a nerdy science and math kid. Whenever I was exposed to proteins, lipids, and enzymes, it all made sense.

Garrett’s research may not have immediate pharmaceutical or medical applications, but it is an important piece in the complex puzzle of cell mechanics. Whether it’s a unicellular organism like Escherichia coli or an 80-trillion-cell organism like an adult human being, the basic metabolic functions of their cells are the same—they build things, and they break things down in order to grow, reproduce, maintain themselves, and respond to environmental changes.

With E. coli (the “tame lab strain”) as her model organism, Garrett and her students are studying the biosynthesis and function of headgroup acylated phospholipids—how the cell builds this particular phospholipid and what it does. “There’s an enzyme in the cell that makes this phospholipid, so we get cells that are genetically mutated to be missing the enzyme, and we also have cells that have more of the enzyme than normal. Then we can ask questions about how the cells function. Do they grow as fast, or do they grow slower? Can they grow at high temps and low temps? Can they handle being exposed to antibiotics? And if we change the lipid composition, what effect does that have on the cell?”

How did she become interested in lipid chemistry? “Growing up, I was always kind of a nerdy science and math kid,” says Garrett. “But whenever I was exposed to bigger, organismal or ecosystem kinds of things, I either wasn’t interested or couldn’t wrap my mind around it. And the same on the other end—the super small, subatomic, quantum side of things.

But whenever I was exposed to cell stuff—proteins and lipids and enzymes—it all made sense and seemed cool.”

A Poughkeepsie native who moved with her family to Florida when she was in high school, Garrett went to Florida State University with the intention of eventually going to medical school. “By second semester freshman year I was doing independent research in biochemistry, and sophomore year I began working with a biology professor, Lloyd Epstein. I worked for him over the summer, and from that time on, it was clear what I was going to do. I loved working in the lab. I just spent all my time in the lab—on weekends, early in the morning. If I wasn’t in class, I was in the lab.”

Her career plan at age 20: “I thought, ‘I’m going to go to graduate school, and then I’m going to get a great postdoc, and then I’m going to start my own lab, and then I’m going to win the Nobel Prize in chemistry!’ And then life happens.”

She earned her PhD from Duke University in 1998 and gave birth to daughter Ariane two months later.

“I took four years off to have my kids,” says Garrett, whose second daughter, Madeline, was born in 2000. “The decision to take a hiatus was lonely. You’re in this environment where everyone around you has decided to work while they have their babies and to put them in daycare, and I didn’t want to do that. So it felt lonely. But then I found out that I was not the person who invented this. Many, many people have done it—female scientists whom I really respected and thought were great had done the same thing, only 20 years earlier. So I’ve made a point of having this be something that’s part of my identity in a much more visible way because I don’t want other young women—or young men, for that matter—to think that no one’s ever done this before. I want them to be able to say to their spouse or their mentor or their postdoc adviser, I can come back, and other people have come back, and they’re very successful.

“Every other year, NYU has a program called ‘What can you do with a PhD?’ and they put together a panel for postdocs and graduate students. I’ve participated in that and I make sure those people know that I took time off, and (a) I got a job, and (b) I got tenure, and (c) I publish papers, and I’m kind of a happy person! So there’s more than one way to do this!”

When she went back to work in 2003, part of her postdoc involved coordinating a basic science course for medical school students, and she also began teaching an undergraduate biochemistry course during the summer session at Duke. “I think that is where I really got the teaching bug,” she says.

Her church also played a role in clarifying her career goals. “We have a Gifts and Talents program at our church, and one of the things that came up was that one of my big strengths is mentoring. And I realized that that was the part of my job that I liked the most—getting the undergraduates all excited about biochemistry and science, and helping the graduate students figure out not just their experiments, but how to function in this intense environment.”

Last year, Garrett completely redesigned the lab component of her biochem class. The outcome, she says, is “amazing.”

At that point, she and her spouse, Chris, and their daughters were at a crossroads. If they were going to make a move, they wanted to do it when their daughters were still in elementary school. “You don’t want it to be when they’re in high school because then you’re going to have to pay for therapy, and middle school is really hard, too, so we said, okay, it’s got to be soon.”

Garrett only considered posts at liberal arts colleges. “I wanted to be someplace where being a good teacher mattered,” she says, “a place where I would be evaluated on how well I did with my teaching as well as my research. So for me, Vassar is the perfect combination.”

Anu Sopeyin ’15, a biochemistry major from Nigeria, has taken several courses with Garrett and began working in her lab second semester freshman year. “Basically, I just went to her office and said, ‘I think your research is really cool. Please consider taking me,’ and she did!” says Sopeyin. “It has been a great experience. She doesn’t spoon-feed you. She challenges you. And you don’t really understand the worth of that until you look back and see where you started from and how much you’ve grown.”

Funded by Vassar’s Center for Collaborative Approaches to Science (which is in turn funded by a grant from the Howard Hughes Medical Institute), Garrett completely redesigned the lab component of the 200-level biochemistry class last year. “We focused on a particular protein, an enzyme called CMP kinase,” she says. “This is an understudied enzyme—there are some things that are known about it, but there’s also a lot we don’t know. So the students worked in groups, and they developed purification protocols, and they developed assays, and they had to come up with a question they wanted to answer about this enzyme and design an experiment.”

Sam Verbanic ’15, a biochemistry major from New Hampshire, says it was completely different from the usual lab course. “Usually you work in pairs, and they give you the lab, and it’s like a cookbook—very straightforward instructions about what you should be doing that day and what you should expect to see. This wasn’t like that.”

Every step of the way, they had options to consider and decisions to make. And the outcome? “It was amazing,” says Garrett. “At the end, when they did their oral presentations, I was so proud I had to choke back tears. I was amazed at how engaged they were and how deeply they had thought about their projects and how they put their presentations together. And teaching the lab this way was so much more fun—I will never go back to doing it the other way.”

Garrett says she has no regrets about the career path she’s taken. “I like that I can actually take the time to interact with my students in a personal way—even if it’s saying something like, ‘Hey—you’re crashing and burning in my class. What’s going on?’ I like that I can spend time helping them with their work, suggesting different approaches to the material, reminding them that they should sleep. I like that I get to be that kind of person instead of the kind who says, ‘Get out of my office, I have a grant to write.’ Feeling that I make a difference in the lives of these students is the thing that I like the best. And when I talk about my job with my group from church, that’s where I see this as me doing what I should be doing, where I feel that my being here has a positive impact on their lives.”

And clearly, it does. “She’s my role model,” says Sopeyin. “She’s a mom, she’s a professor, she’s a runner. And she definitely mentors me, not only on science but life. So for me it’s like a whole round experience, and I am grateful for that.”