CAREER: Molecular Genetic Analysis of the Dictyostelium discoideum Developmental Regulator FbxA -- A Strategy for Integrating Research and Teaching

这个项目描述了在阿勒格尼学院的本科生物学课程中整合研究和教学的策略。PI的研究兴趣集中于了解在发育过程中建立和维持不同细胞命运的机制。她使用细胞黏液霉菌盘基网柄菌作为她的实验系统。Nelson博士对FbxA的分析有三个具体目标：1)确定FbxA调控的信号通路(S)的特征；2)表征FbxA的结构、功能和转录调控；3)使用网柄基菌作为工具，结合本科水平的研究实验室工作。FbxA是通过靶向蛋白质降解调节发育信号通路的蛋白质家族的成员。确定FbxA介导的降解目标是确定FbxA调节哪些发育途径的关键一步。将采用两种并行的方法来实现这一目标。FbxA本身也将通过确定其细胞类型特定的角色、创建显性负等位基因和启动子分析而得到更完整的表征。有针对性的蛋白质降解作为一种发育调节机制的重要性现在才被认识到。对FbxA及其调控的途径(S)进行更详细的分析，可能会对这一不断增长的领域做出重大贡献。这个职业项目说明了如何使用Dictyostelials，这既是学生可以接触到的，也是愿意接受复杂的分子遗传分析的，可以将研究整合到各级课程的课程中。通过初级研讨会和高级项目要求，阿勒格尼生物系成功地让本科生参与独立研究的历史由来已久。该奖项支持在一门新的实验室课程--生物学290：生物学中的调查方法--中使用网盘基菌，使研究培训成为入门课程中不可或缺的一部分。学生将以小组形式设计和执行独立的实验。实验设计和解释方面的帮助将作为每周讨论部分的一部分提供。学生专题将在书面报告和口头报告中达到高潮。这份提案描述了几套相关的为期四周的单元，纳入了对FbxA的调查提出的研究问题，并向学生介绍了各种技术。

This project describes a strategy for integrating research and teaching in the undergraduate Biology curriculum at Allegheny College. The research interests of the PI, Dr. Margaret K. Nelson, focus on understanding the mechanisms by which distinct cell fates are established and maintained over the course of development. She uses the cellular slime mold Dictyostelium discoideum as her experimental system. Dr. Nelson's analysis of FbxA, a protein that regulates several aspects of development, has three specific aims: 1) to identify of the signaling pathway(s) regulated by FbxA, 2) to characterize FbxA structure, function, and transcriptional regulation, and 3) to use Dictyostelium as a vehicle for incorporating investigative labwork at the introductory undergraduate level. FbxA is a member of a family of proteins that regulate developmental signaling pathways via targeted protein degradation. Identifying the targets of FbxA-mediated degradation is a crucial step in determining which developmental pathways FbxA regulates. Two parallel approaches will be employed to achieve this goal. FbxA itself will also be more completely characterized, via determination of its cell type-specific roles, creation of a dominant-negative allele, and promoter analysis. The importance of targeted protein degradation as a developmental regulatory mechanism is only now being realized. More detailed analysis of FbxA and the pathway(s) it regulates is likely to make a significant contribution to this growing field. This CAREER project illustrates how Dictyostelium, which is both student-accessible and amenable to sophisticated molecular genetic analysis, can be used to integrate research into courses at all levels of the curriculum. Through its junior seminar and senior project requirements, the Allegheny Biology Department has a long history of successfully involving undergraduates in independent research. This award supports the use of Dictyostelium in a new laboratory course, Biology 290: Investigative Approaches in Biology, making research training an integral part of the introductory curriculum. Students will work in small groups to design and execute independent experiments. Assistance with experimental design and interpretation will be provided as part of a weekly discussion section. Student projects will culminate in written and oral presentations. This proposal describes several related sets of four-week modules, incorporating research questions raised by investigations of FbxA and introducing students to a variety of techniques.