Indrani Bose, Ph.D. - US grants

Intellectual Merit:
The overall goal of this research is to define the mechanism and role of the enzyme acetate kinase. Acetate kinase catalyzes the interconversion of acetate and acetylCoA. As acetylCoA is a key metabolite at the crossroads of many metabolic pathways, understanding acetate kinase structure, function and regulation is key to understanding basic metabolism. Although previously thought to be present primarily in bacteria, acetate kinase has now been identified in eukaryotic microbes such as fungi and protozoans. Initial characterization of acetate kinases from these organisms has revealed unique properties, suggesting that the acetate kinase enzyme family is far more diverse than previously thought. The biochemical differences between bacterial and eukaryotic acetate kinases suggest that this enzyme may serve a different physiological function in eukaryotes. This is further evidenced by the fact that phosphotransacetylase, an enzyme that functions with acetate kinase in bacteria, is absent in fungi and protozoans. The specific aims of this project are to understand the basis for the biochemical differences among the eukaryotic and bacterial acetate kinases and to determine the roles of this enzyme in fungi and protozoans. This will be the first investigation of eukaryotic acetate kinases and should shed light on additional physiological roles for this enzyme and provide unique insights into the biochemical mechanism of this important metabolic enzyme. Furthermore, acetate kinase is part of a wide family of related enzymes, which includes hexokinase, other sugar kinases, actin and Hsp70 heat shock proteins; these studies will thus provide insight into evolution of this enzyme superfamily.

Broader Impacts:
The project has a broad educational impact at the graduate, undergraduate, and high school levels. The research provides a wealth of projects for students at all levels of education and ability. Projects will afford training in biochemistry, molecular biology, and microbial cell biology. Graduate students will play an essential role and will each direct an undergraduate student as well, providing an important mentoring opportunity. The research will involve high school students from the Summer Program for Research Interns at Clemson University. In addition to providing a number of graduate and undergraduate research projects at both Clemson University and Western Carolina University, this joint project also offers the Western Carolina students greater exposure to a Ph.D.-granting research university. Students involved in this project will present their research at state and regional scientific meetings as well as national meetings.