CAREER: Distinct Functions of Cdk4 and Cdk6

该职业计划旨在将康涅狄格学院的本科分子生物学课程与细胞周期研究相结合。 职业目标是在细胞周期调控方面建立一个富有成效的研究计划，并将该研究纳入本科课程教学和指导本科研究。细胞周期调控是年轻科学家感兴趣的，因为它在许多生物过程中起着重要的作用，如发育，分化和癌症。具体的研究目标是区分两种高度同源的细胞周期蛋白依赖性激酶（cdk），cdk 4和cdk 6的功能，这两种激酶都在大多数细胞类型中表达。虽然认为cdk4和cdk6具有冗余的功能并且都调节细胞增殖，但越来越多的证据表明cdk4和cdk6也可能具有不同的功能。 数据表明，某些细胞类型可能只特异性扩增两种激酶中的一种，这表明cdk4和cdk6可能在特定细胞类型中受到不同的调节或具有不同的功能。 解决这一假设的目的是基于初步的数据表明，cdk4和cdk6的功能，可以区分在星形胶质细胞模型。实验将研究这些激酶的特性，这些特性可能导致在表达这些激酶中的一种或另一种的星形胶质细胞中观察到cdk4和cdk6的增殖、形态和定位的差异。生物化学实验，以调查这些差异的设计，使本科研究人员可以成功地执行它们。使用一种新的双杂交系统的文库筛选将筛选出特异于cdk6而非cdk4的相互作用蛋白。这个屏幕将被纳入康涅狄格学院的分子生物学课程，并将由本科生进行，作为他们的实验室课程的一部分。学院的使命是把科研纳入本科生的教育中，这将很好地服务于这里提出的研究和学生的科学发展。康涅狄格学院和辉瑞制药公司之间正在进行的合作伙伴关系也将为学术和工业合作提供一个独特的机会，作为该项目的一部分。

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.