CAREER: Distinct Functions of Cdk4 and Cdk6

本职业课程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节方面建立一个富有成效的研究项目，并将该研究纳入本科课程教学和指导本科生研究。年轻科学家对细胞周期调控很感兴趣，因为它在许多生物过程中起着如此重要的作用，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（cdks）， cdk4和cdk6的功能，这两种激酶在大多数细胞类型中都有表达。虽然人们认为cdk4和cdk6具有冗余功能，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数据，这些数据表明cdk4和cdk6的功能可以在星形胶质细胞模型中区分出来。实验将研究这些激酶的特性，这些特性可能导致在表达其中一种激酶或另一种激酶的星形胶质细胞中cdk4和cdk6在增殖、形态和定位方面的差异。研究这些差异的生化实验是为了让本科生研究人员能够成功地进行这些实验而设计的。使用新型双杂交系统的文库筛选将筛选cdk6特异性而非cdk4特异性的相互作用蛋白。该筛选将被纳入康涅狄格学院的分子生物学课程，并将由本科生作为实验课程的一部分进行。学院的使命是将研究纳入本科生的教育，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的持续合作关系也将为该项目的学术和工业合作提供独特的机会。

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.