NSF Award
9983736
9983736<br/>Li<br/>GTPases are molecular switches that regulate diverse cellular functions via binding and hydrolyzing GTP. In many cases, however, the mechanism by which the GTPase cycle is coupled to biological function is unknown. The long-term goal of this project is to employ a multidisciplinary approach to obtain a thorough understanding of the chemical principle and the biological function of GTPases. This goal will be accomplished through a series of research and education initiatives. The research project focuses on the Rab5 GTPase. The Rab family of GTPases regulates specific intracellular trafficking events. Rab5 in particular is localized to the cytoplasmic side of early endosomes and is important for early endosome fusion, an essential step of endocytosis. In this project, the mechanism of Rab5 GTPase activity, its regulation by a newly identified GTPase-activating protein (GAP), and its specific function in endosome fusion will be investigated by using experimental techniques of cell biology, molecular biology, biochemistry, and biophysics. The structural determinants of Rab5 that are important for the specific interaction with the GAP will be determined, as well <br/>as the structural determinants of Rab5 that are important for its unique intrinsic GTPase activity. The large number of Rab GTPases not only share common properties but also show individual differences, including the quantitative difference in GTPase activity and the qualitative difference in functional specificity. The molecular basis of these differences is unclear. This project should help clarify these issues and will have a significant impact on the fundamental mechanism of GTPase activity as well as the specific Rab5 function in regulating endosome fusion. <br/><br/>In this Career award, the current knowledge and cutting-edge research on GTPases and GTPase-mediated biological functions will be integrated into an education initiative, which focuses on the development of a graduate course entitled "multidisciplinary approach to biological problems" to explore new ways of teaching. This course will encourage students to think and solve biological problems from the perspectives of not only biology but also chemistry, physics, and mathematics. An effective way to teach this course is to use specific examples. In this regard, the GTPase superfamily of proteins provides a rich resource for understanding the principles of physical structure, chemical kinetics, and biological function. This course will help overcome the barrier and cultivate a collaborative spirit across disciplines and better prepare biology students for careers in academia and industry.
