SUMMER AT THE BENCH: UNRAVELING GENOMIC IMPRINTING

This summer, Bryn Mawr College undergraduates experienced life as full-time scientists by pursuing mentored research projects on campus as part of the College's Undergraduate Summer Science Research Program. This two-part series looks at two research groups. This week, we'll focus on a group that investigated genomic imprinting under the supervision of a biology professor; next week: a group of young chemists' efforts to synthesize analogs of natural products used in drug development.

From left: Jennifer Gerfen, Lu Mei He, Geneva Stein and Tamara Davis

"The program has helped me realize that this is really what I want to do," says Geneva Stein '06, who did her research in the lab of Tamara Davis, associate professor of biology. "I like learning about molecular biology and learning about the process — for example, why and how we use PCR," says Stein, a biology major who plans to attend graduate school.

Since 1989 the College has provided 35 to 45 students annually with 10-week research stipends to conduct independent research with faculty members. In addition to their work in the lab, students attend weekly seminars and participate in a poster session to present their research to faculty and students. They earn academic credit for research performed in their junior or senior years, and they often co-author articles in scientific journals with their faculty mentors and present their findings at professional meetings.

Investigating Genetic Imprinting

Tamara Davis' lab focuses on the mechanism of genomic imprinting. In mammals, there are several genes for which only the maternally inherited copy is expressed, as well as some for which only the paternally inherited copy is expressed. In genetic imprinting, the maternal and paternal alleles are marked, enabling the cellular machinery to distinguish between them. Imprinting is believed to be controlled by DNA methylation, or bonding of a methyl group to the cytosine residue of a CpG dinucleotide, one of the basic structural units of DNA. Davis' group is analyzing methylated patterns in imprinted genes during different stages of gamete development in the mouse to determine when methylation occurs.

For their summer projects, Stein and Lu Mei He '06 investigated methylation acquisition on the paternal allele of the mouse gene Gtl2. Stein, who also worked on the project during the summer of 2004, admits to having been "a little scared" at the prospect of an independent project at the very beginning. "I expected it to be more professor-driven," she recalls. But the nervousness soon wore off, Stein says, and she decided to return to the lab in 2005 because "I felt very dedicated to it and wanted to see the project through."

He, an English major/biology minor, did research at Memorial Sloan-Kettering Cancer Center in the summer of 2004. While that experience offered the opportunity to interact with many different biological researchers, she says, pursuing a project on campus enables her to continue her investigations after the summer ends. She is considering attending medical school and combining research with clinical studies.

Jennifer Gerfen '06 analyzed the influence of the methylation state on gene expression in Davis' lab. Gerfen, a biology major who worked with the mouse gene Rasgrf1, previously did research for five summers at the National Institutes of Health. "At the NIH I was part of a project, but it wasn't so much my project," she says. "Here, I have the ability to troubleshoot when something is going wrong." Gerfen, who has done cell and molecular biology research, says the experience has helped to clarify her career plans. "I had been wavering as to what kind of research to go into. But doing something that's entirely molecular has influenced me."

Because all three students had previous research experience, "they came in very well-versed in molecular biology techniques in the lab and were able to work independently quickly," Davis says. "I didn't leave them entirely to their own devices, but I encouraged them to do their own thing and come to me when they have questions. It's a pleasure — and a little bit of a surprise — when I can go away for a day and they don't need me."

He says she appreciates Davis' mentoring style: "Professor Davis definitely wants the students in her lab to get their hands dirty. I think that's what research is like in the real world — a good mentor will guide you, but it's a personal experience."

Davis notes that the undergraduates' summer research experience is "a very different experience from what they get doing their research part-time during the academic year." While classes are in session, she notes, "they're much more distracted; there's a number of things pulling at their time." During the summer, "I teach them how to multitask so they're not bored, and I allow them to do more of their own troubleshooting, because they have more time."

At one point in the summer, Stein experienced a disappointing setback. She thought she had identified a difference in the genetic code that would distinguish between maternally and paternally inherited copies of the gene. "I found a difference," she recalls, "but it was due to a mistake in one of the amplifications." Davis explained to her that false data are a fact of research life. "She is now trying to figure out if there are other differences between the two strains," Davis says.

Gerfen obtained a very interesting result from her experiments — one that was contrary to the group's expectations. They had expected that the methylation of one region was controlling the expression of her gene, but her findings indicated that the difference in methylation is not the only factor influencing the differences in expression.

"Her result was very exciting," Davis says. "I communicated it to my colleagues. It is pointing us in a totally different direction in terms of experimental approach." Gerfen expects to continue investigating what factors are influencing gene expression during the fall.

In late July, Davis, He and Gerfen traveled to Quebec for a meeting of the Society for the Study of Reproduction, where the students presented posters. "It's good to have a colleague-like experience — to get a chance to share my ideas and get advice on where to go from here," He says.

"It's a pleasure to see them so excited about what they're doing," Davis observes.

—by Barbara Spector, for Bryn Mawr S & T

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