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

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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.