RUI: Chromatin Dynamics and Transcription in Drosophila melanogaster

智力优势：该项目的目标是利用果蝇强大的遗传系统来了解细胞中DNA是如何管理的以及基因是如何被调节的。在真核细胞中，DNA与组蛋白相互作用形成一种叫做染色质的结构。染色质结构和功能受染色质修饰酶和染色质重塑因子的调控。这些蛋白质如何产生和维持染色质结构，以允许适当的基因表达在整个生物体的发展是非常有趣的。PI的长期目标是了解染色质重塑因子如何调节染色质的动态性质。本项目主要研究黑腹果蝇CHD1染色质重塑因子及其在组蛋白动态跨基因调控基因表达中的作用。实验将验证CHD1染色质重塑因子调节组蛋白跨基因动力学以对抗抑制性染色质的工作假设。参与这些过程的蛋白质是高度保守的；因此，这些对黑腹果蝇的研究应该适用于包括人类在内的其他生物。PI将采用遗传，分子和细胞生物学工具和技术，这是染色体形态，基因沉默和组蛋白动力学研究的理想选择。这项工作非常适合PI的本科生实验室，因为果蝇遗传学特别适合学生研究。更广泛的影响：来自克莱蒙特麦肯纳、斯克里普斯和皮策学院的本科生将进行大部分研究。在她在W.M.凯克科学系的前9年里，PI在她的研究实验室指导了43名本科生（37名女性和6名男性），其中包括3名拉丁裔学生，3名非裔美国学生和几名第一代大学生。研究生通常在实验室呆一到三年。在这个项目的三年里，PI将为10-15名本科生提供实质性的（通常是多年的）研究经验，为他们提供帮助他们在自己选择的职业中取得成功的技能。三所顶级文理学院共享PI独特的跨学科部门。该系大约70%的理工科毕业生是女性，部分原因是来自斯克里普斯女子学院的大量理工科毕业生。凯克理学院每四名学生中就有一名是少数族裔，该系15%的学生来自科学领域代表性不足的少数族裔。因此，学生团体将PI置于鼓励来自历史上代表性不足群体的理工科学生的位置。作为这项研究的一部分，本科生将参加包括年度果蝇研究会议和Asilomar染色质和染色体会议在内的国家会议并展示他们的工作。

Intellectual Merit: The goal of this project is to use the powerful genetic system of Drosophila melanogaster (the fruit fly) to understand how DNA is managed in the cell and how genes are regulated. In eukaryotic cells, DNA interacts with histone proteins to form a structure called chromatin. Chromatin structure and function is regulated by chromatin modifying enzymes and chromatin remodeling factors. How these proteins generate and maintain chromatin structures to allow proper gene expression throughout the development of an organism is of great interest. The PI's long-term goal is to understand how chromatin remodeling factors regulate the dynamic nature of chromatin. This project is focused on the Drosophila melanogaster CHD1 chromatin remodeling factor and its roles in regulating histone dynamics across genes to regulate gene expression. Experiments will test the working hypothesis that the CHD1 chromatin remodeling factor regulates histone dynamics across genes to antagonize repressive chromatin. The proteins involved in these processes are highly conserved; these studies in Drosophila melanogaster should therefore be applicable to other organisms, including humans. The PI will employ genetic, molecular, and cell biological tools and techniques, which are ideal for the investigation of chromosome morphology, gene silencing and histone dynamics. This work is ideally suited for the PI's undergraduate laboratory, as Drosophila genetics is especially amenable to student research. Broader impacts: Undergraduate students from Claremont McKenna, Scripps, and Pitzer Colleges will carry out most of the research. During her first nine years in the W.M. Keck Science Department, the PI mentored 43 undergraduates in her research laboratory (37 women and 6 men), including three Latina students, three African-American students, and several first-generation college students. Research students typically spend one to three years in the laboratory. Over the three years of this project, the PI will provide a substantive (often multi-year) research experience for 10-15 undergraduates, providing them with skills to help them succeed in their chosen careers. Three top-tier liberal arts institutions share the PI's unique interdisciplinary department. Approximately 70% of the department's science graduates are women, partially due to a large number of science majors from Scripps, an all-women's college. One of every four Keck Science students is an ethnic minority, and fifteen percent of the department's students are from ethnic groups underrepresented in the sciences. The student body therefore places the PI in the position to encourage science students from historically underrepresented groups. As part of this research, undergraduates will attend and present their work at national conferences including the Annual Drosophila Research Conference and the Asilomar Chromatin and Chromosomes conference.