Unraveling DNA Mysteries

Megan Núñez

Photo by Richard Howard

Megan Núñez has devoted her career to solving microscopic mysteries, drawing on chemistry, biology, and physics while gathering clues and asking questions that bring her closer to answers.

Fortunately, Núñez, a professor of chemistry, is well-equipped for scientific detective work. In fact, it is this process of asking and answering questions that first drew her to research: She remembers herself as a child so brimming with curiosity that she was constantly asking her parents “why?” Later, as a chemistry student at Smith College, she stepped of the classroom and into the lab, where she was instantly transfixed by the seemingly infinite number of questions in front of her.

And for Núñez, there is no better target for her questions than the cell. “I feel like the cell is kind of like Russian dolls,” she says. “Every time you solve one problem, you open it up and there’s another one on the inside, and then you open that up and there’s another one, and they just go on forever.”

Her most recent mystery started with a broad question: What happens when DNA inside a cell is damaged? Núñez, along with an ever-rotating fleet of students, has spent more than a decade on the hunt for a tiny DNA lesion, 8-oxoguanine, that occurs when an extra oxygen atom is added onto guanine, one of the four DNA bases.

“That one atom can then cause your DNA to be mispaired and lead to mutations, and so we’re interested in: What does it look like? How does it lead to the miscopying? How do the repair proteins find it when it’s so small?” Núñez explains.

After working her way through different techniques, Núñez finally found success with single molecule experiments, where she takes an individual piece of DNA, “yanks on it like a shoelace” with a pair of optical tweezers and looks for tiny changes in the way it behaves. Using this approach, she was able to measure differences between regular and damaged DNA, thus pinpointing the lesion. She published these findings in March in Nucleic Acids Research.

Núñez is also investigating another DNA lesion called spiroiminodihydantoin that forms when two oxygen molecules are added onto a guanine base. She is also studying bacterial adhesions—how bacteria stick to surfaces and other bacteria—using an atomic force microscope that pokes and prods cells, forcing them to reveal their physical properties.

“It’s hard to put a distinct tag on what I do because I work at the interface between disciplines,” says Núñez. “But I really like that because by taking from some of the techniques of other disciplines, you can then answer questions that you couldn’t answer otherwise.”

Yet for Núñez, her favorite part of her job isn’t answering complex research questions. Rather, it is working with students—guiding them, collaborating with them, and supporting them as they grow into capable, self-assured scientists.

“I think that young women don’t usually see themselves as scientists. It’s not that picture that they ever grow up having, and so seeing that transformation of that view of themselves is really exciting and wonderful,” says Núñez.

She is committed to improving the educational experience for the entire Wellesley student body. As part of the College’s Inclusive Excellence Working Group, Núñez and other faculty members have been grappling with issues like how race and class affect students’ academic experience.

“We’ve had a lot of small programs that have been effective for groups of students, but we want to figure out how to make it universal, so that all of our students have this universally strong experience when they’re here, and they feel valued no matter what,” she says, adding that recently, conversations have centered on how to ensure every student is being equally heard during group projects.

While Núñez is confident that she and her colleagues will eventually achieve these goals, she also recognizes that with a continual influx of new students, slowing down isn’t an option. “You have to keep at it,” she says. “It’s like being at the seashore with your sandcastle—the water is just constantly eroding it, so you have to keep building and building and building.”

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