Mechanisms of Centromere Assembly in Drosophila

果蝇着丝粒组装机制

• 批准号: 1024973
• 负责人: Barbara Mellone
• 金额: $ 78.31万
• 依托单位: University of Connecticut
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1024973&HistoricalAwards=false
• 关键词: Mechanisms; Centromere; Assembly; Drosophila

Scientific Research:A hallmark of successful cell division is the accurate segregation of chromosomes to daughter cells during mitosis and meiosis. Understanding how cells mediate this critical event is central to understanding genome stability and, conversely, how its failure contributes to genetic abnormalities in cells and organisms. The centromere is a specialized structure present on all chromosomes that is absolutely essential for chromosome segregation because it provides the physical location for chromosomes to attach to spindle microtubules and be distributed equally to daughter cells. Even though a large number of centromeric components have been identified to date, particularly in humans, only a subset can be identified in the genome of Drosophila melanogaster. Furthermore, increasing new evidence suggests that the centromeres of Drosophila are regulated differently from those of the other eukaryotes analyzed so far. This raises the important question of whether pathways responsible for centromere function are conserved among different organisms. Characterizing this process in Drosophila, a model system that offers powerful cell biology and genetics, will ultimately contribute to a comparative understanding of centromere biology that will provide further insights into this fundamental phenomenon across species. Specifically, this project will identify novel components involved in centromere structure and function and define their role in pathways that mediate maintenance of the centromere through multiple cell divisions. In addition, an exciting new role for the cell cycle in regulating these processes will be further investigated. These goals will be achieved using an alliance of cell biological, molecular and biochemical methodologies to fill major gaps in our knowledge of the intriguing world of chromosome biology.Broader Impacts:This project includes ample opportunities for collaborative research exposing undergraduate and graduate students to the interdisciplinary nature of modern scientific investigation. An additional educational goal is to establish a comprehensive hands-on module that exposes students to cutting-edge cell division research including the latest methods in timelapse microscopy. Key outreach efforts are the promulgation of visual tools for the dissemination of knowledge about chromosome segregation and cell division to middle and high school students, teachers and the general public; the participation in initiatives to attract and develop the next generation of female scientists; and the involvement in programs exposing high school students to laboratory research.

科学研究：成功的细胞分裂的一个标志是在有丝分裂和减数分裂期间染色体准确地分离到子细胞。了解细胞如何介导这一关键事件是理解基因组稳定性的核心，反过来，它的失败如何导致细胞和生物体中的遗传异常。着丝粒是存在于所有染色体上的一种特殊结构，它对染色体分离是绝对必要的，因为它为染色体附着在纺锤体微管上并均匀分布到子细胞提供了物理位置。尽管迄今为止已经鉴定出大量的着丝粒成分，特别是在人类中，但在果蝇的基因组中只能鉴定出一个子集。此外，越来越多的新证据表明，果蝇的着丝粒受到的调节与迄今为止分析的其他真核生物的着丝粒不同。这就提出了一个重要的问题，即负责着丝粒功能的途径是否在不同的生物体中是保守的。在果蝇中描述这一过程，一个提供强大的细胞生物学和遗传学的模型系统，最终将有助于对着丝粒生物学的比较理解，这将为跨物种的这一基本现象提供进一步的见解。具体来说，该项目将确定参与着丝粒结构和功能的新成分，并确定它们在通过多次细胞分裂介导着丝粒维持的途径中的作用。此外，将进一步研究细胞周期在调节这些过程中的一个令人兴奋的新作用。这些目标将通过细胞生物学、分子生物学和生物化学方法的联合来实现，以填补我们对染色体生物学这一有趣世界的知识的主要空白。更广泛的影响：该项目包括大量的合作研究机会，使本科生和研究生接触到现代科学研究的跨学科性质。一个额外的教育目标是建立一个全面的动手模块，使学生接触到尖端的细胞分裂研究，包括在延时显微镜的最新方法。主要的外联工作是颁布视觉工具，以便向初高中学生、教师和一般公众传播关于染色体分离和细胞分裂的知识；参与吸引和培养下一代女科学家的倡议；以及参与让高中生接触实验室研究的项目。