RUI: Investigations into the Role of the CHD1 ATPase in Chromosome Structure in Drosophila

智力优势：在真核细胞中，DNA与组蛋白相互作用形成一种称为染色质的结构，其基本单位是核小体。虽然染色质曾经被认为是惰性的，只存在于组织和压缩DNA，但现在很清楚，染色质可以主动控制基因的表达。因此，正确的染色质结构的形成和维持至关重要。这个项目的目标是利用果蝇(果蝇)强大的分子和遗传工具来了解基因表达过程中染色质结构是如何保持的。该研究的重点是染色质重塑因子CHD1的作用。CHD1是一种高度保守的ATPase，定位于转录活性基因。该项目解决了特定的假设，即CHD1针对活性基因，以促进转录后的染色质重组，从而调节全球染色体结构。这一假说将通过两个特定的目标得到验证：(1)研究CHD1丢失或增加后染色质组成和组蛋白修饰的变化，以及(2)使用生化方法和新的遗传分析相结合的方法识别与CHD1功能相互作用的蛋白质。为了达到这些目标，研究人员将使用各种遗传、生化和细胞生物学工具和技术，这些工具和技术是研究染色体形态的理想工具。广泛的影响：了解在基因表达过程中染色体结构是如何保持的，与我们对细胞生物学的基本理解有关。这项研究的一个更直接的影响是本科生的参与。克莱蒙特学院麦肯纳学院、斯克里普斯学院和匹泽学院的本科生将在调查人员的指导下进行大部分研究。这三所顶尖的文科院校共享研究人员的独特部门(联合科学系，由物理学家、化学家和生物学家组成)。大多数理科专业的学生将研究作为毕业论文的一部分，许多学生在二年级或三年级就开始进行研究。在这个项目的三年时间里，调查员将为10-15岁的本科生提供大量(通常是多年)的研究经验，为他们提供技能，帮助他们在研究生教育和他们选择的职业中取得成功。这将允许本科生真正拥有自己的项目，并在通常为研究生保留的水平上参与研究。高级本科生将有机会参加年轻本科生的培训，让他们深入了解如何教授科学并解释如何进行研究。

Intellectual Merit:In eukaryotic cells, DNA interacts with histone proteins to form a structure called chromatin, the basic unit of which is the nucleosome. While chromatin was once thought to be inert, present only to organize and compact the DNA, it is now clear that chromatin can actively control gene expression. Formation and maintenance of the correct chromatin structure is therefore critical. The goal of this project is to use the powerful molecular and genetic tools of Drosophila melanogaster (the fruit fly) to understand how the structure of chromatin is maintained during gene expression. The research focuses on the role of the chromatin remodeling factor CHD1. CHD1 (chromodomain, helicase, DNA-binding domain protein) is a highly conserved ATPase that is localized to transcriptionally active genes. This project addresses the specific hypothesis that CHD1 is targeted to active genes to promote chromatin reassembly in the wake of transcription, thereby modulating global chromosome structure. This hypothesis will be tested through two specific aims: (1) Investigate changes in chromatin composition and histone modifications following loss or gain of CHD1, and (2) Identify proteins that functionally interact with CHD1 using a biochemical approach complemented with a novel genetic assay. To address these aims the investigator will employ a variety of genetic, biochemical, and cell biological tools and techniques that are ideal for the investigation of chromosome morphology.Broader impacts: The understanding of how chromosome structure is maintained during gene expression is relevant to our basic understanding of cell biology. A more immediate impact of this research is the involvement of undergraduates. Undergraduate students from Claremont McKenna, Scripps, and Pitzer Colleges of the Claremont Colleges will carry out much of this research under the mentorship of the investigator. These three top-tier liberal arts institutions share the investigator's unique department (The Joint Science Department, consisting of physicists, chemists, and biologists). Most of the science majors conduct research as part of a senior thesis, and many students begin research in their sophomore or junior years. Over the three years of this project, the investigator will provide a substantial (often multi-year) research experience for 10-15 undergraduates, providing them with skills to help them succeed in postgraduate education and in their chosen careers. This will allow undergraduates to have true ownership of their own projects, and participate in research at a level usually reserved for graduate students. Senior level undergraduates will have the opportunity to participate in the training of younger undergraduates, giving them insights into how to teach science and explain how research is done.