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Summer of Science
By Barbara Spector
This summer, Bryn Mawr College undergraduates experienced life as a full-time scientist by pursuing mentored research projects on campus as part of the College's Undergraduate Summer Science Research Program.
"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.
Each year since 1989 the College has provided 35 to 45 students 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 often co-author articles in scientific journals with their faculty mentors and present their findings at professional meetings.
Investigating Genetic Imprinting
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From left: Jennifer Gerfen, Lu Mei He, Geneva Stein and Tamara Davis
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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. 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."
Mentored Independence
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."
Surprising Discoveries
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.
Creating Analogs of Natural Products
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From left: Shauna Bennett, William Malachowski, Jisun Lee and Ronke Imbeah-Ampiah
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Chemistry majors Jisun Lee '06, Ronke Imbeah-Ampiah '06 and Shauna Bennett '07 spent the summer in the lab of William Malachowski, assistant professor of chemistry. Malachowski's research focuses on devising efficient methods to make analogs of complex natural products that are used in drug development.
Lee's project involved a method of synthesizing quaternary carbons that combines two reactions: the Birch reduction-allylation and the stereospecific Cope rearrangement. Her ultimate aim is to use the procedure to synthesize (+)-lycoramine, an analog of (-)-galanthamine, which has been approved for treatment of Alzheimer's disease. "The Birch reaction and the Cope reaction were put together in sequence before, but not to make this particular compound," explains Lee. "Basically, if the Birch-Cope sequence works to make the proposed compound, then it would mean that this is a new way to make the natural product." Lee who plans to incorporate the project into her thesis, spent part of the summer making starting materials that are not commercially available and testing the versatility of the Birch-Cope allylation reaction.
Lee had previously done research in a neuroscience lab at a medical school in her native Korea. She plans to take the MCAT exam but is also contemplating graduate school. "I've always been interested in clinical studies," she says. The focus on drug synthesis has given her a new perspective, she explains. "I would like to get involved in analyzing drugs."
Lee says she learned an essential lesson during her summer experience: "I was reminded every day that it is important to be careful and take time to think through each and every step of a reaction. The result really shows in the purity and the yield of your product."
Posing Questions
Malachowski's mentoring strategy involves "closer supervision in the beginning, so the students experience some progress," he explains. "Then I back away slowly and see how things go. Initially, I try to explain things to them. At about three weeks in, I encourage them to think about posing questions to themselves about what may have occurred when something goes wrong. Hopefully, the training wheels are off, and they don't even have to leave their hood and come to me."
Imbeah-Ampiah and Bennett aimed to synthesize inhibitors of the enzyme indoleamine-2, 3-dioxygenase (IDO). Tumor cells express IDO, which catalyzes the cleavage of tryptophan, an amino acid. IDO also has been linked to immunosuppression in cancer. Imbeah-Ampiah also worked in Malachowski's lab in the summer of 2004 and hopes the research will serve as a foundation for her thesis.
"Last summer was my first time in the lab and I didn't have too much experience," Imbeah-Ampiah recalls. "But I'm used to the methods and more comfortable this summer." The experience has given her a taste of science's challenges, she says. "There are always questions to ask in the lab. You can do an experiment every day of the week, but every day is different. It's a wonderful experience to put theory into practice." She hopes to pursue a graduate degree in medicinal chemistry and work in either academia or the pharmaceutical industry.
Gaining Confidence
After Malachowski explained the techniques to her, Bennett recalls, "I was surprised that I could handle myself in the lab. I had no prior experience working in a lab and had no idea of what to expect."
She says she prefers full-time research to her lab classes. "In class, you worry about getting your work done and doing it right, but you don't really worry about the chemistry. In the lab, you really care about what you make. I'm happy when I purify something and see the product come out."
The summer research projects are "not only an intellectually stimulating experience in terms of the students' personal growth," Malachowski says. "In addition, there's the practical element. They're learning skills in the lab that are considered valuable in the chemical community, particularly in the pharmaceutical industry. They definitely are benefiting both intellectually and personally."
Barbara Spector writes on science and technology as well as business topics. She is the editor-in-chief of Family Business magazine and former editor of The Scientist .
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