Frontiers

Digging Deeper

Undergraduate Tariro Mupombwa probes the mechanisms of energy production in tuberculosis bacteria.
December 2009

Among the many cultural differences Tariro Mupombwa, C’10, experienced when she first came to Penn from Zimbabwe was that of classroom expectations. While it was an adjustment for the biochemistry major to address her professors by their first names, still more startling was the intensity of class participation.

“In Zimbabwe, students were basically expected to give answers to whatever the professors asked of them,” Mupombwa says. “Here, they teach you how to go beyond memorizing the answer. Sometimes I’d be surprised by the suggestions students would make in class, which was something I was not used to.” But Mupombwa wholly embraced this entrepreneurial spirit of learning while conducting research with Dr. Harvey Rubin, Professor of Medicine.

Having witnessed the suffering caused by HIV/AIDS in her homeland, Mupombwa arrived at Penn with a profound interest in studying infectious diseases. During her sophomore year, she was directed to Rubin’s lab, which explores the genetic and metabolic regulatory networks that allow tuberculosis bacteria to persist long-term in human hosts.

Working with Rubin and Dr. Takahiro Yano, Mupombwa is studying an enzyme called NDH-2 that is critical to energy production in tuberculosis bacteria. She is trying to identify the enzyme’s binding region because this knowledge could contribute to the formulation of inhibitors that can interrupt the binding process.

“If we understand where the binding region of this enzyme is, we can come up with inhibitors that will stop energy production, which will result in the bacteria dying,” she explains.

"Research is open-ended. If you know what you're going to get, then I think it means you're not doing research anymore. The whole purpose is to keep digging deeper and trying different options to learn something new." – Tariro Mupombwa

To conduct this study, Mupombwa designs mutant bacteria with altered versions of NDH-2, and she then tests the mutants’ ability to produce energy. “If the mutation is important, then the enzyme will be unable to function properly,” she says. So far, two of the mutants Mupombwa has created show significantly impaired enzymatic activity, and she is in the process of investigating whether or not this phenotype is actually a result of the mutation. Another mutant is showing lower-than-normal levels of activity, and Mupombwa is embarking on further experiments to figure out why.

The opportunity to collaborate with colleagues is one of the aspects of her research experience that Mupombwa most enjoys. “I’ve realized you can’t do research on your own,” she says. “I enjoy talking, not only to people in my lab, but also to other peers who are doing research. It’s encouraging to hear them say, ‘I’ve been through the same situation—maybe you should try doing this.’ ”

Mupombwa believes the support of peers is crucial when dealing with the ups and downs inherent in research. “An important thing to keep in mind,” she says, “is that research is open-ended. If you know what you’re going to get, then I think it means you’re not doing research anymore. The whole purpose is to keep digging deeper and trying different options to learn something new. I’ve had to throw out the results of multi-day experiments, and it’s definitely frustrating when something like that happens. But then I’ll sleep on it and come back energetic the next day.”

Mupombwa’s activities at Penn are a testament to that energy. In addition to conducting her research, she founded a service project in which she partnered with the Salvation Army to collect and send 31 sewing machines to Zimbabwe. Recipients included residents of a senior care facility as well as a training program for garment making run by the Salvation Army. Mupombwa is currently in the process of applying to medical school, where she hopes to continue pursuing research on infectious diseases and drug discovery.