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Characterization of a novel, evolutionarily distinct chaperone for centromeric histone H3

一种新颖的、进化上独特的着丝粒组蛋白 H3 伴侣的表征

基本信息

批准号：
1330667
负责人：
Barbara Mellone
金额：
$ 51万
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：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2018-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1330667&HistoricalAwards=false
关键词：
Characterization novel evolutionarily distinct chaperone

项目摘要

This research will take an evolutionary approach to understand how centromeres assemble. Centromeres are essential elements of chromosomes that are crucial for proper transmission of genetic information from cell to cell during cell division. When centromeres fail to assemble correctly, the result can be an imbalance in chromosome number whereby cells have too many or too few chromosomes. In animals, such an imbalance can lead to visible developmental defects, which in turn can lead to birth defects or death. This study aims to impact our understanding of the conserved aspects of centromere assembly, and hence aspects that are crucial for preventing an imbalance in chromosome number and catastrophic developmental defects. In addition, this research will have a strong educational impact by providing opportunities for undergraduate and graduate students to engage directly in research and by developing a new hands-on summer laboratory workshop for high school teachers to enable them to learn about chromosome biology and take the lessons learned back to their high school classrooms.In eukaryotes, centromeres assemble by binding special centromere-specific histone H3 proteins, which are escorted to the correct location on the chromosome by chaperone proteins. Recent results have revealed structural and sequence variation in these chaperones, which suggests that during evolution, multiple mechanisms may have arisen for assembling centromeres. This work will focus on analysis of the chaperone proteins using evolutionary, structural and functional studies. Comparisons will be made among a newly discovered chaperone from Drosophila and two well-conserved chaperones from yeast and mouse. The outcomes of the work will provide unique mechanistic and evolutionary insights into the fundamental processes that govern centromere structure and function. The project will also have broad impact from the educational perspective. The research will be carried out by undergraduate and graduate students, many of whom are women, thereby providing opportunities for scientific training, career development and direct participation in the promulgation of scientific findings through publications and conference presentations. In addition, a novel hands-on summer laboratory workshop will be developed for high school teachers (ten per year), focusing on the basic biology of chromosome segregation and cell division and extending to emerging topics such as stem cells and altered genetic states in cancer. The teachers will leave the workshop armed with teaching materials, ideas for lesson plans, and positive research experiences through their direct involvement in experimentation. By enabling the teachers to take what they learn back to their classrooms, the workshops will have a multiplier effect on the scientific education of scores of pre-college level students.

这项研究将采取进化的方法来了解着丝粒是如何组装的。着丝粒是染色体的基本元素，对于细胞分裂期间细胞间遗传信息的正确传递至关重要。当着丝粒不能正确组装时，结果可能是染色体数量的不平衡，即细胞具有太多或太少的染色体。在动物中，这种不平衡可能导致明显的发育缺陷，进而导致出生缺陷或死亡。这项研究的目的是影响我们对着丝粒组装保守方面的理解，从而对防止染色体数量失衡和灾难性发育缺陷至关重要。此外，这项研究将通过为本科生和研究生提供直接参与研究的机会，并为高中教师开发一个新的实践暑期实验室讲习班，使他们能够了解染色体生物学，并将学到的经验教训带回高中课堂，从而产生强大的教育影响。在真核生物中，着丝粒通过结合特殊的着丝粒特异性组蛋白H3蛋白进行组装，它们被伴侣蛋白护送到染色体上的正确位置。最近的研究结果揭示了这些分子伴侣的结构和序列变异，这表明在进化过程中，可能出现了多种机制组装着丝粒。这项工作将侧重于分子伴侣蛋白的进化，结构和功能的研究分析。将在一个新发现的果蝇伴侣蛋白和两个保守的酵母和小鼠伴侣蛋白之间进行比较。这项工作的成果将为控制着丝粒结构和功能的基本过程提供独特的机制和进化见解。该项目还将从教育角度产生广泛影响。这项研究将由本科生和研究生进行，其中许多是妇女，从而提供科学培训、职业发展和通过出版物和会议发言直接参与公布科学成果的机会。此外，还将为高中教师开发一个新颖的动手夏季实验室研讨会（每年10个），重点是染色体分离和细胞分裂的基础生物学，并扩展到干细胞和癌症遗传状态改变等新兴主题。教师将离开车间武装教材，教案的想法，并通过他们的直接参与实验积极的研究经验。通过使教师能够把他们学到的东西带回课堂，讲习班将对数十名大学预科学生的科学教育产生倍增效应。