Bryn Mawr College
A quarterly newsletter on research, teaching, management, policy making and leadership in Science and Technology

Summer at the Bench
By Barbara Spector

What are the rewards and challenges of a research career? Last summer, a select group of Bryn Mawr College students got a glimpse of the answer through participation in the 13-year-old Undergraduate Summer Science Research Program.

For Sook Chan ’04, the experience offered an introduction to basic science. "As a chemistry major, it really helps to spend at least one summer in the lab, just to gain a better understanding of scientific research," says Chan, one of five undergraduates mentored by William P. Malachowski, assistant professor of chemistry.

Team Malachowski (from left) Tina Morgan Ross, Katherine Wang ’03, Rob Broadrup, Sook Yee Chan ’04, Rachel Kahn ’03, Sadie White ’03, William Malachoski and Chenyang Tie

Rachel Kahn ’03, who also worked in Malachowski’s lab, notes that "summer lab work is good preparation for the independent research and thesis of senior year at Bryn Mawr." The experience also grooms students for graduate school or work in industry and helps to distinguish them from their peers, adds Kahn, a chemistry major.

Protease Inhibition

Malachowski’s lab is synthesizing molecules that resemble proteins but are altered structurally to inhibit the activity of protease enzymes, which catalyze cleavage of the amide bond in proteins. This leads to the degradation of proteins, a factor in diseases such as rheumatoid arthritis, emphysema, artherosclerosis, cystic fibrosis and pancreatitis.

Malachowski’s group is developing beta-lactam protease inhibitors, which inhibit the enzyme process by mimicking the structure of the natural substrate. The group plans to conduct enzyme-inhibition studies to determine whether the beta-lactam molecules actually do inhibit proteases.

"What we hope to contribute is intellectual inspiration for drug developers," Malachowski explains.

Last summer in Malachowski’s lab, Kahn and Katherine Wang ’03 synthesized beta-lactams, protein mimics with a four-membered ring structure in a crucial enzyme attack site. Kahn’s objective was to synthesize a beta-lactam protease inhibitor for porcine pancreatic elastase, a relatively inexpensive serine protease related to human leukocyte elastase. Wang’s project involved adding a methyl group to the beta-lactam ring to assess whether increased selectivity or enhanced reactivity would result.

Sadie White ’03 attempted to create a mimic with a five-membered ring in this site. "The responses of proteases to this structure will be compared to their interactions with structures including four-membered rings to determine if one type is a more effective inhibitor than the other," explains White, a chemistry major.

Chan’s goal was to make a seven-membered ring in order to assess its efficiency in enzyme inhibition. Elisa Jimenez ’03 aimed to synthesize a beta-lactam to target papain, a protease found in papaya that uses a cysteine residue to cleave peptide bonds.

"I feel fortunate to be working with students who are this bright," Malachowski says. "There’s a joy you get out of seeing people learn and understand."

Malachowski encourages the undergraduates to devise their own approaches rather than constantly seek his advice. "They have different levels of independence as they mature as scientists — and as they mature as people, too," he says.

Discoveries Made

"Research has taught me to remain tenacious, humble and good-humored in the face of complications," White says. "Much like all of life, laboratory work is unpredictable in its pattern of successes and failures."

Chan compares lab research to a treasure hunt. "Sometimes, one finds all the clues and is successful, and sometimes one doesn’t," she points out. "Yet when a reaction fails or doesn’t work, I’ve learned that it does not reflect my abilities; things just don’t work sometimes."

"I’ve learned to work more slowly, be more careful and become less ambitious, at times," says Wang, a double major in biology and English. "Instead of setting up three reactions and getting three poor yields as a result of having rushed through the follow-up work, it is better to get one good, clean yield."

Rewards of Discovery

The summer research experience offers other benefits as well. Malachowski is currently drafting a paper incorporating experiments done by Wang, who worked in his lab throughout the 2001-02 academic year. Wang will be a co-author of the paper, which will be submitted to a major scientific journal. "That’s a clear indication of her productivity," Malachowski notes.

In September, participants in the summer program presented their research at an in-house poster session. Kahn, whose research is funded by Pfizer, will also give a presentation at the pharmaceutical company. She gave a similar presentation last fall at Bristol-Myers Squibb, which funded her summer 2001 research. "I got a lot of positive feedback and good ideas from researchers for improving reactions that failed," Kahn recalls.

This summer, Bristol-Myers Squibb funded Chan’s work in Malachowski’s lab. Wang’s research was funded through the General Electric Faculty for the Future Program and Bryn Mawr College. White was supported through a grant from the Dorothy Nepper Marshall Fellowship Fund, which also includes a teaching project that she will develop in 2002-03. Jimenez, a chemistry major, was supported by Bryn Mawr College.

Data Analysis (from left) Sabah Quraishi ’03, Peter Brodfuehrer and Kuorkor Dzani ’04

Studying Swimming

Kuorkor Dzani ’04 and Sabah Quraishi ’03 — who spent the summer in the lab of Peter D. Brodfuehrer, associate professor and chair of biology — say their shared experiences have forged a bond between them. "In the beginning, neither of us had any background in research," says Quraishi, a biology major. "As our skills on a basic level increased, the research brought us together."

"It’s an interesting dynamic," says Brodfuehrer. "They’ve learned to work with one another; they’ve each learned which things they do well."

At the start of the summer, "I was a little apprehensive," admits Dzani, who’s majoring in biology and English. But the experience has turned out to be "really great," she reports. "It’s not just learning biology; you have to learn techniques and how to analyze your results."

Brodfuehrer’s lab is investigating the initiation of swimming behavior in Hirudo medicinalis, the medicinal leech. The leech is a useful organism to study, Brodfuehrer explains, because it exhibits a limited range of behaviors and has relatively few neurons. Researchers can easily manipulate leech neurons to study how the nervous system controls swimming, a rhythmic behavior. Insights from these experiments can be applied to other systems, such as breathing in mammals, which is also a rhythmic behavior, Brodfuehrer notes.

Dzani and Quraishi used the isolated nerve cord of the leech to investigate the underlying cellular mechanism that produces long-term activation of neurons associated with generating leech swimming behavior. "Our goal is to see what channels are involved, what ions are involved and whether it’s a voltage-dependent process," Brodfuehrer says.

No Smooth Sailing

It wasn’t always smooth sailing, the two students report. In the first half of the summer, they attempted to assess the effect of a channel-blocking drug on neuronal excitation. They tried to determine whether the drug would block activity when they passed current through the nerve cells. "We got some results and thought it was due to the drug," Dzani explains. But there was one hitch: They hadn’t done their control experiments first. When they finally did do the controls, they found to their dismay that "the activity was not due to the drug but rather to the alcohol we used to dissolve the drug," Dzani says.

The discovery, though disappointing, taught Dzani some important lessons, she notes: "Do your controls early, be willing to learn, and keep on trying. You’re not expected to make an earth-shattering discovery; you’re there to learn."

Dzani and Quraishi have come a long way, Brodfuehrer reflects. "It’s a pretty steep learning curve, but they’ve done a really good job," he says. At the beginning of the summer, "they’d read some of my papers, but they were unfamiliar with doing the work and what information you get out of it."

Screen Time (from left) Thida Aye ’04 and Alphonso Albano

Signal Results

Dzani and Quraishi’s summer research was funded by a National Science Foundation grant awarded jointly to Brodfuehrer and Alfonso M. Albano, the Marion Reilly Professor of Physics. Albano’s portion of the project involves nonlinear analysis of electrophysiological signals associated with the swimming reflex in the leech. Thida Aye ’04 spent the summer developing algorithms to analyze time-series measurements from the leech experiments in Brodfuehrer’s lab.

"We aim to determine the differences between the signals generated in the leech ventral cord that result in swimming and non-swimming behavior when the leech is stimulated," explains Aye, who’s double majoring in physics and mathematics with a minor in economics. "For my part of the project, I’m concentrating on the possible disparity between signals that turn out to be nonlinear and elicit swimming, and non-swimming actions of the leech before the stimulation."

Aye notes that this "real-life research work" is more cross-disciplinary than her coursework. "For example, you have a mathematical idea, and then you apply it to physical and biological systems," she says. "This is a good project to see how the other disciplines approach their work."

Challenging Experience

Mentoring an undergraduate poses challenges because of the short duration of the summer session, Albano notes. "You have to pick a project that can be done in a reasonably short time — or a small part of a long-term project, as in this case," he says. In addition, he points out, the project must be tailored to the students’ level of experience. "They come to you clean," Albano says. "What they have are basic skills and, one hopes, some interest."

Aye acknowledges that her research was "a bit harder than I thought, since the project involves a programming method that I’m not very familiar with. I had to learn it from scratch, but now I can say I’m fairly good at it."

Albano says that before they spend time in a lab, undergraduates tend to have "a romanticized view of research." The summer experience informs their career decisions by teaching them that occasionally scientific experimentation involves frustration and tedium.

Evidently, Aye — who spent last summer doing research with Victor Donnay, associate professor and chair of mathematics — has learned this lesson. "Both of my summer research projects taught me that you have to be patient and motivated," she says. "You can’t expect to find significant results every single day. Some days you are just doing number punching, so to speak. Some days you can get a lead and the project will take a step forward.

"You don’t know what’s going to happen."

Summertime Science

Bryn Mawr College’s Undergraduate Summer Science Research Program, established in 1989, is open to students in biology, chemistry, computer science, geology, mathematics, physics and psychology. The program is funded by government agencies, nonprofit foundations, corporate donations, and endowments by alumnae and friends of the College, as well as by the College’s own funds.

Faculty members mentor students for 10 weeks of independent research. The undergraduates spend 40 hours per week doing computational research, fieldwork, or hands-on laboratory experimentation. The summer program also includes seminars designed to introduce students to science careers. In summer 2002, 36 students collaborated with 17 faculty members on 33 research projects.

About the Author

Barbara Spector writes on science and technology as well as business topics. She is the executive editor of Family Business magazine and former editor of The Scientist.