Volume 18 • Issue 2

Small School, Big Science

Story and photography by R. Bryant Hill

Senior biology major Bryce Foster works with Assistant Professor Maria Todd studying abnormalities in “cell cycle” genes and their role in cancer.

Leading a larger trend in undergraduate education, small, private liberal arts universities like Southwestern are rapidly gaining a reputation as fertile ground for the next generation of scientists and some of the academy’s most interesting and challenging scientific research.

No longer are groundbreaking scientific endeavors solely undertaken at the large, research universities. Nor are science faculty looking only to engage the lab assistance of the best and brightest among this year’s crop of graduate students and postdoctoral fellows. More and more, undergraduates are granted access to significant research opportunities and given lab responsibilities once reserved for doctoral students. According to a Feb. 25, 2007, article in USA Today by Justin Pope of The Associated Press, “Traditionally, undergraduate education has taken place in the classroom, while research has been for graduate students and faculty. No more. Colleges and universities are pushing hard to get many more undergraduates involved in research.”

A Robin Wilson article titled “A Hothouse for Female Scientists,” appearing in the May 5, 2006, issue of The Chronicle of Higher Education, echoed this sentiment, stating, “Research universities have top-of-the-line laboratories, the most accomplished researchers and giant federal grants. But they don’t hold a monopoly on preparing future scientists.”

Many colleges and universities, especially at research universities, have increased undergraduate research opportunities because of market pressures within the increasingly competitive arena of undergraduate student recruitment. “It’s good for their reputation, which depends on students moving on to the next level,” says Pope. “Undergraduate research has become almost a prerequisite for top graduate programs. That’s a big reason demand is skyrocketing.”

Maria Todd, assistant professor of biology

More than anything else, this opens the door for undergraduates in the sciences to gain great research experience. Pope goes on to point out that greater emphasis is placed on the learning opportunities afforded by involving undergraduates in scientific research than on pushing them to achieve great breakthroughs in their fields of inquiry. Still, some exceed perhaps even their faculty collaborators’ expectations and earn the opportunity to present at national scientific conferences and symposia or earn prestigious National Science Foundation grants—as several Southwestern students have done in recent years.

Such experience is invaluable to undergraduates as they prepare for the next phase of their scientific careers—be it graduate school or the workplace. “Not only are undergraduate researchers more engaged in their subject,” notes Pope, “but they also appear to improve more broadly in teamwork and collegiality—skills employers value but complain students don’t typically learn in class.”

Pope also notes that many faculty find involving undergraduates in research especially challenging. After all, not all undergraduates—even those majoring in the natural sciences and planning to pursue advanced scientific research or medical degrees—are prepared to conduct research or play a significant role in the research method. Some may see it as an important stepping stone, but lack the drive and initiative to carve out necessary laboratory hours amidst an already hectic undergraduate schedule full of academic and social commitments.

This can be especially true on smaller, residential campuses where there exists a strong tendency toward students sometimes overextending themselves with all the academic, social, athletic and organizational opportunities typically available. Martín Gonzalez, assistant professor of biology at Southwestern, admits that there have only been a handful of undergraduates during his tenure who have been able to really put in all the time and effort necessary to sustain an individual research project because their schedules are so busy.

Pictured left to right: Senior Michelle Martinez, Junior Amber Hoerauf, and Maha Zewail-Foote, assistant professor of chemistry

Nonetheless, the simple fact that undergraduates studying the sciences at small liberal arts universities work so closely with science faculty and even have a chance to develop their own research projects puts them far ahead of their peers at most larger universities. According to Carolina Boet ’06, studying with Maria Cuevas, assistant professor of biology, “Working in Dr. Cuevas’ lab gives one a similar type of independence to what one would get in a graduate program.” She continues, “Students are responsible for their projects’ progress. Under Dr. Cuevas’ mentorship, students are responsible for primary literature review and current findings in the field. It is the students’ responsibility to keep bringing new essays, experiments and ideas to the project.”

Senior Tracey Einem, another of Cuevas’ undergraduate research students, adds, “While initial training is necessary, students are able to design their own experiments in accordance with Cuevas’ ‘big picture’ research goals. Students also participate in the analysis of results, which truly inspires independent learning.” This is one of the major goals of the liberal arts tradition, to instill in students a passion for learning and to nurture an individual passion and drive for the acquisition of knowledge, even if for the sake of knowledge alone. Einem also is one of 20 students nationwide to be offered an internship at the National Institutes of Health.

The opportunity to develop their research skills, to hone their methodologies and instrumentation skills under the direct supervision of a faculty researcher, is of immeasurable benefit.

Scientific inquiry is driven by a similar passion. Gonzalez notes, “My love of science and curiosity inspire my work. I do what I do simply to know how things work. As a child, didn’t you ever take something apart just because you wanted to understand how it worked? I’m just a big kid with bad knees.”

“Working in the laboratory, students learn about the process of science. This imparts to them an appreciation of the dedication required to succeed in science and an understanding that all the information they listen to in lectures and read in their textbooks is the result of years, if not decades, of tough, hard work and persistence,” says Gonzalez. “They learn that science is as much about negative results—and how to deal with them—as it is about success. In my opinion, there are few greater joys in life than the sense of discovery. Students obtain great satisfaction from knowing that the data they teased from an organism is unknown to the world until we present/publish the results.” He concludes, “The ultimate benefit of the research we do in my lab will not be measured by the results we generate from our experiments, but by the interest the lab experience sparks in these young individuals to go out, advance their education, and make discoveries that will benefit us all.”

Junior Jason Burnham

Big Science

That’s not to say that there isn’t some rather astounding scientific work being done in the labs at smaller universities across the country. His modesty aside, Gonzalez and his students engage in important research on DNA repair and mutagenesis in E. coli bacteria. He explains, “When DNA is damaged in bacteria, a set of genes are turned on that are the ‘last resort’ for the organism’s survival. The two proteins made from these genes make up a DNA polymerase that is capable of copying damaged DNA. In non-stress situations,” Gonzalez says, “the DNA polymerase responsible for copying DNA is unable to copy DNA that is damaged. Students in my lab study how these ‘last resort’ proteins are regulated.”

Gonzalez and his students employ numerous techniques in the lab—knocking genes out of organisms to assess their role in DNA repair, using site-directed mutagenesis, which involves introducing specific mutations into genes of interest to assess the import of that area to gene function, and regularly performing gene splicing.

This E. coli research project is funded by the National Institutes of Health. While the work itself offers many benefits from a basic science standpoint, it is also significant for its potential in understanding bacteria resistance mechanisms. The ‘last resort’ process studied by Gonzalez and his students is one of the mechanisms that bacteria have evolved to resist antibiotics. Research like theirs helps develop a better understanding for exactly how these organisms evolve their defenses and, hopefully, will lead to methods for circumventing them.

Several faculty at Southwestern conduct research aimed at understanding cancer, perhaps the major challenge to human longevity. Cuevas has been involved with two research endeavors in this area. One of her research projects “examines the cytotoxic effect of anthrapyrazoles, which are organic compounds that intercalate with DNA, and attempts to elucidate the molecular mechanisms behind their effect,” she says. The promise of this research lies in the understanding created by examining these cellular mechanisms. It is Cuevas’ hope that such understanding will demonstrate how these specific compounds work and how they might be harnessed to “control and/or stop the unregulated cell proliferation that is seen in cancer.”

Martín Gonzalez, assistant professor of biology, helps Jason Burnham check his work.

Cuevas also is involved with research on tamoxifen, a widely used drug for the treatment of some types of breast cancer, with several other faculty at Southwestern. According to Cuevas, “Tamoxifen blocks the actions of estrogen.” Which is why it can be an effective treatment in breast cancer. But, as Cuevas explains, “In the endometrium (inner lining of the uterus) tamoxifen acts like estrogen.” Funding for this research comes from the Merck Science Institute.

Maha Zewail-Foote, assistant professor of chemistry, also involved in tamoxifen research, explains further, “The human body metabolizes tamoxifen into derivatives that can react with DNA to form tamoxifen-DNA adducts. These adducts can potentially alter DNA replication, gene expression and, ultimately, disrupt the normal cell cycle, a molecular hallmark of cancer.” She continues, “We are currently examining which DNA sequences are most vulnerable to reacting with these derivatives as well as the structural and biological consequences of the resulting adducts. This will help shed light on the mechanisms underlying the induction of the endometrial tumors by tamoxifen. Such information could have important ramifications for the prevention and treatment of the most prevalent cancer in women today.”

Zewail-Foote does additional research on the anti-cancer drug daunomycin. This work is funded by a highly competitive PRF grant from the American Chemical Society. Specifically, she and her students are “characterizing the types of DNA damage that result from photoactivation of daunomycin and the role of oxygen in this process.” Daunomycin has been shown to produce oxygen radicals in the presence of light, explains Zewail-Foote, which may contribute to “daunomycin’s enhanced anti-cancer activity in the presence of light.” She says, “These studies will enrich our current understanding into the alternate anti-cancer mechanisms of daunomycin, which could lead to better design of cancer therapeutics.”

Maria Todd, assistant professor of biology, also conducts cancer research, but her work is focused on the genes that lead to the development of cancer. “Numerous genes and their protein products are required to ensure the regulated growth and division of normal (non-tumor) cells,” explains Todd. “Deregulation of one or more of these genes has been found to lead to uncontrolled cellular proliferation, the accumulation of further gene mutation(s) and the subsequent development of a tumor. My lab studies the role of abnormalities in these ‘cell cycle’ genes in the development of ovarian and breast cancers.”

In her research work prior to joining the Southwestern faculty, Todd identified cyclin E, a key cell cycle gene “whose protein product is aberrantly elevated in multiple ovarian and breast tumors.” Since arriving at Southwestern, Todd has involved several undergraduates, including Kristen Meerbrey ’06 and senior Shea Spruill, in her research efforts and found continued success in working with cyclin E. While at Southwestern, she has managed “both to characterize the stability of cyclin E and to restrict cyclin E protein expression in ovarian cancer cells.” In other words, she has been successful at suppressing the growth of ovarian cancer cells. Her current research with Spruill is aimed at regulating cyclin E in ovarian cancer cells during which time the growth characteristics of the cancer cells will be assessed and compared to the growth characteristics of non-tumor cells.

“Identification of specific genetic defects in cancers of a particular pathology is critical if we are to develop more reliable screening methods for cancers in the early stages of development,” says Todd. “Additionally, once we know what causes cancer at the genetic level, we can design gene-based therapies (such as the suppression of cyclin E described above) tailored to treat the specific cause of a patient’s tumor.”

Undergraduates at smaller institutions like Southwestern, given the above, have very rich and significant opportunities. The opportunity to develop their research skills, to hone their methodologies and instrumentation skills under the direct supervision of a faculty researcher, is of immeasurable benefit. They also gain preparation for a variety of careers and the confidence to pursue their own research interests, their own answers to tough questions. Returning to Pope, there is “a growing recognition that—whether it’s science or literature or history—research seems to do students all sorts of good, even if they don’t make a career out of it.” Even if they do make a career of it, those fortunate enough to have worked with teacher/researchers like Todd and others mentioned here, will be ready to hit the ground running toward the next major scientific breakthrough and, maybe, it might just turn out to be the breakthrough that really does save the world.

Saving the World

“I have always been interested in energy and the different ways in which things are powered,” says Southwestern first-year student Pelham Keahey. “As nonrenewable resources are running out and energy costs keep rising, it is really important for us to find a new reliable energy source that can, quite literally, power the world. But, until we accomplish that, we have to make every little bit count.”

Enter solar power. Keahey came to Southwestern with a very strong background in physics and an obvious interest in energy. Seeing a student who needed a challenge, Steve Alexander, associate professor of physics, urged Keahey to develop a research project and apply for funding from the King Creativity Fund. Says Alexander, “Given his solid background, our department wanted to see if there was some way we could enhance his first-year experience. After discussing several topics, we wandered around to the subject of energy and decided to see if we could construct a low-cost solar water heater.”

Alexander goes on to explain that designing “an efficient solar collector will involve an understanding of optics, a bit about thermodynamics and even a bit about astronomy.” The goal for the project is to construct a solar-powered water heater that would cost about $100 and be able to heat enough hot water each day for a family of four. “In short,” says Alexander, “we want to save the world.”

FYI…

From 2004-2006, more than half of all Southwestern’s natural science majors have gone on to graduate study in the sciences or to medical school. Southwestern, too, is a hotbed for female scientists with several recent graduates garnering National Science Foundation Fellowships for their doctoral study. Among them:

Frances Chu ‘02 Biology/Chemistry double-major now at Harvard
Kimberly lrson ‘04 Chemistry major now at Berkeley
Ana Alcaraz ‘03 Chemistry major now at Emory
Janel Owens ‘03 Chemistry major now at University of California–Davis