Angela Koehler: Hands-on at Harvard
By Karen Hopkin

It's 7 a.m. and Angela Koehler sits at the lab computer, answering e-mail, downloading journal articles, and checking the latest basketball scores. "I'm a huge fan," Koehler confesses, and catching up on NBA action in the early hours means that fewer people will be around to tease her.

Like most academic labs, the Schreiber suite is sparsely populated before 9 a.m. "I like it that way," says Koehler, who is a graduate student working with HHMI investigator Stuart Schreiber in Harvard's Department of Chemistry and Chemical Biology. "There's never any competition for equipment, so I can get a lot done between 7 and 10." After logging off, Koehler typically spends her morning at the bench: growing cell cultures, running chemical reactions, or purifying the proteins and small molecules she needs for her studies. After lunch, she crunches numbers and analyzes the day's data. By 7 p.m., Koehler is ready to head home—unless it's a Friday, in which case, the whole lab retires to the courtyard for its weekly "beverage bash."

It's hard work, but Koehler enjoys putting in the hours and working with her hands. "I like the small challenges, the manual tasks," she explains. Spending half a day in the cold room coaxing a single protein from a complex mix of cellular soup or coming up with the correct conditions to isolate the compound she wants—"it's like a game," says Koehler. "It's fun."

Koehler didn't start out as a chemist. In fact, chemistry was the subject that interested her the least. Growing up in Oregon, Koehler was drawn into science by the eruption of Mount St. Helens in neighboring Washington State. By the age of five or six, she was devouring books about volcanoes, planets, dinosaurs, and other heady topics.

Koehler entered college as a biology major but soon discovered that she longed to understand the world at the level of the molecule. "I didn't want to see proteins drawn as colored blobs," she says. But it wasn't until her junior year at Reed College in Portland—when Koehler signed up for courses in synthetic chemistry and animal physiology—that she found her calling. "In chemistry class we'd synthesize some natural product," she says. "Then I'd go to physiology class, where we'd treat cells with this compound to see what would happen. But no one ever explained how it worked." Now, in Schreiber's lab, Koehler tackles that question head on as she studies how drugs and other small molecules affect living systems.

In her current project, Koehler is developing techniques for simultaneously observing the interactions that occur between thousands of small molecules and the proteins to which they bind. With the help of specialized robots, Koehler makes glass slides coated with 10,000 or so different compounds, dips these slides into different solutions of purified protein, and then checks to see which molecules stick to which proteins. By monitoring millions of these interactions, Koehler hopes to isolate molecules that bind specifically to proteins that are physiologically important. For example, one compound she studied adheres tightly to E2, a protein made by the virus that causes cervical cancer. Now Koehler and her colleagues are testing to see whether her compound, or one like it, might someday be used as a drug to treat or prevent this deadly form of cancer.

After four years in the Schreiber lab, Koehler is preparing to defend her thesis. She'll then continue to work on her project for a year or two as an independent fellow in Harvard's Molecular Target Lab, which Schreiber now directs. As for the future, Koehler sees herself staying in academia, even though she may be a tad jealous of her buddies who took "real jobs" after college. "They're all driving around in their new sports cars," she remarks. "I don't even have a car."

Not that she needs one in Cambridge. A quick trip on the subway pretty much gets her where she needs to go. But accessibility isn't the area's only attraction. "I can't imagine not being here in the fall," says Koehler. "The colors are amazing. And everyone is so excited about going back to school," which is different from her experience in southern California. "In Pasadena, people laugh at you when you say you're a student," she says. "They think it's dorky."

Of course there's nothing dorky about Koehler, except maybe her approach to boiling a lobster. After scouring her cookbooks for the perfect protocol, she gathers her reagents and then meticulously adjusts the brine in the lobster pot to exactly the right salinity. "Come to think of it," she says, "it's just like working in the lab."

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