RIG: Biophysical Characterization of Cdc42Hs Forms Associated with Cell Transformation

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This project will study the structure and dynamics of Cdc42Hs forms associated with its ability to affect the normal processes of cell signaling and proliferation. Cdc42Hs is a member of the Ras superfamily of Rho GTP-binding signal transduction proteins, which binds guanine nucleotides and acts as a molecular timing switch in multiple signal transduction pathways. Mutations in Cdc42Hs and other Ras proteins have been shown to lead to uncontrolled cell proliferation. In this project various deletion mutants of Cdc42Hs will be used to determine the effect of mutation on the conformation of this protein and its ability to bind to its effectors, in order to gain a better understanding of the processes by which changes in Cdc42Hs and its interaction with regulators affect various important signal transduction pathways. NMR and fluorescence spectroscopy will be used as tools to characterize the structural and dynamic effects of the apo form of Cdc42Hs. Dr. Adams has previously characterized the wild type Cdc42Hs and will use similar analytical tools to study the mutant forms. Broader Impacts: It is believed that the structural and molecular characterization of these Cdc42Hs constructs will have a broad importance to society by providing a basic understanding of the role that protein structure and flexibility play in facilitating protein-protein interactions that regulate cell signaling and intercellular communication. Perhaps the most important impact of this project is that it will allow an underrepresented minority investigator to develop an independent research program for the first time. The fundamental results will be presented to upper level undergraduate and graduate students, providing the investigator the chance to interact with and provide training to students. The time period allotted for this project will allow for the development of nurturing/mentoring skills by the investigator as they relate to the promotion of participation of underrepresented minorities in science. The investigator will interact with minority undergraduate students interested in science in programs such as the Cornell University College of Arts and Sciences Minority COSEP (Committee of Special Educational Projects) program, where the investigator has spoken with minority students in the past. This time will also be used to establish networks with other, more established minority scientists through involvement in scientific conferences, such as the Biophysical Society and the Protein Society, particularly with minority affairs committees for each society.