This CAREER program is designed to integrate undergraduate molecular biology coursework with cell cycle research at Connecticut College. The career objective is to establish a productive research program in cell cycle regulation and to integrate that research into teaching undergraduate courses and guiding undergraduate research. Cell cycle regulation is interesting to young scientists since it plays such an important role in so many biological processes, such as development, differentiation and cancer. Specific research objectives are to distinguish the functions of two highly homologous cyclin dependent kinases (cdks), cdk4 and cdk6, both of which are expressed in most cell types. While it is believed that cdk4 and cdk6 have redundant functions and that both regulate cellular proliferation, an increasing body of evidence suggests that cdk4 and cdk6 may also have distinct functions. Data indicate that some cell types may specifically amplify only one of the two kinases, suggesting the hypothesis that cdk4 and cdk6 may be differently regulated or have different functions in specific cell types. Aims addressing this hypothesis are based on preliminary data which demonstrate that cdk4 and cdk6 functions can be distinguished in an astrocyte cell model. Experiments will investigate those properties of the kinases that may lead to observed differences in proliferation, morphology and localization of cdk4 and cdk6 in astrocytes expressing one or the other of these kinases. Biochemical experiments to investigate these differences are designed so that undergraduate researchers can successfully perform them. A library screen using a novel two-hybrid system will screen for interacting proteins specific for cdk6 and not cdk4. This screen will be incorporated into the molecular biology course at Connecticut College and will be carried out by undergraduate students as part of their laboratory coursework. The research proposed here and the scientific development of the students will be well served by the college's mission to incorporate research into the education of undergraduate students. An ongoing partnership between Connecticut College and Pfizer Pharmaceuticals will also provide a unique opportunity for academic and industrial collaboration as part of this project.
