Student research provides new insights into cellular machinery of Chagas' disease parasite
Michelle Oppenheimer of Charlotte, N.C., a Ph.D. student in biochemistry in the College of Agriculture and Life Sciences at Virginia Tech, has received a two-year $46,000 fellowship from the American Heart Association to advance her research on a parasite that causes Chagas' disease, which can lead to swelling and inflammation of the heart.
The parasite, Trypasonoma cruzi, is carried primarily by the blood-sucking bug known as vinchuca or “kissing bug” (Triatoma infestans), which is rampant in South America. As a result, Chagas' disease infects millions of people.
The parasite cell surface allows it to evade the victim’s immune system. An important component of the cell surface is the sugar, Galatofuranose (Galf). Oppenheimer is studying the enzyme, UDP-galactopyranose mutase, that produces Galf. Since Galf is absent in humans, the cellular processes that produce it may provide a target for a drug treatment with few or no side effects.
Oppenheimer traveled to the University of Alberta in Canada to learn how to synthesize a substrate, which is the molecule that the enzyme acts upon or converts to a specific product. She has developed an assay specific to the T. cruzi enzyme in order to measure its activity. Her project involves site-directed mutagenesis to understand the role of certain amino acids in catalysis and the use of alternative substrates, or mimics, to probe the mechanism of action of the enzyme.
"The ultimate goal is to understand the chemical mechanism and use the information for rational drug design," said Oppenheimer's major professor, Pablo Sobrado, assistant professor of biochemistry.
Oppenheimer said, "I am interested in understanding how proteins function and enjoy doing research that has an application to human health." Chagas was of particular interest because it presently has no effective treatment, she said.
Galf is also produced on the cell surface in other disease-causing parasites, which may offer broader applications for drugs to inhibit its production.
Oppenheimer's research to understand how the T. cruzi enzyme works complements Sobrado's research for the National Institutes of Health-funded Drug Development Consortium for Chagas' Disease. His group is using a high through-put assay to test products from drug libraries as inhibitors of the T. cruzi enzyme.
With a score of "excellent," Oppenheimer ranked in the top three percent among 109 applicants from the Mid-Atlantic region for the American Heart Association fellowship, Sobrado said.