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
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
Rachel Kahn 03, who
also worked in Malachowskis 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
Malachowskis 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.
Malachowskis 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
"What we hope to contribute
is intellectual inspiration for drug developers,"
Last summer in Malachowskis
lab, Kahn and Katherine Wang 03 synthesized
beta-lactams, protein mimics with a four-membered
ring structure in a crucial enzyme attack site.
Kahns objective was to synthesize a beta-lactam
protease inhibitor for porcine pancreatic elastase,
a relatively inexpensive serine protease related
to human leukocyte elastase. Wangs 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
Chans 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. "Theres 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.
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
Chan compares lab research
to a treasure hunt. "Sometimes, one finds
all the clues and is successful, and sometimes
one doesnt," she points out. "Yet
when a reaction fails or doesnt work, Ive
learned that it does not reflect my abilities;
things just dont work sometimes."
"Ive 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,
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. "Thats a clear
indication of her productivity," Malachowski
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 Chans work in Malachowskis
lab. Wangs 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.
Analysis (from left) Sabah
Quraishi 03, Peter Brodfuehrer
and Kuorkor Dzani 04
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."
an interesting dynamic," says Brodfuehrer.
"Theyve learned to work with one another;
theyve each learned which things they do
At the start of the summer,
"I was a little apprehensive," admits
Dzani, whos majoring in biology and English.
But the experience has turned out to be "really
great," she reports. "Its not
just learning biology; you have to learn techniques
and how to analyze your results."
Brodfuehrers 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,
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 its a voltage-dependent
process," Brodfuehrer says.
It wasnt 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 hadnt
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. Youre not expected to
make an earth-shattering discovery; youre
there to learn."
Dzani and Quraishi have come
a long way, Brodfuehrer reflects. "Its
a pretty steep learning curve, but theyve
done a really good job," he says. At the
beginning of the summer, "theyd read
some of my papers, but they were unfamiliar with
doing the work and what information you
get out of it."
Time (from left) Thida Aye 04
and Alphonso Albano
Dzani and Quraishis
summer research was funded by a National Science
Foundation grant awarded jointly to Brodfuehrer
and Alfonso M. Albano, the Marion Reilly Professor
of Physics. Albanos 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 Brodfuehrers
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, whos
double majoring in physics and mathematics with
a minor in economics. "For my part of the
project, Im 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."
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
Aye acknowledges that her
research was "a bit harder than I thought,
since the project involves a programming method
that Im not very familiar with. I had to
learn it from scratch, but now I can say Im
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
cant 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 dont know
whats going to happen."
Bryn Mawr Colleges 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 Colleges 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.