CAREER: Investigations of Methylation, Mobile Elements and Hybrid Genomic Instability

职业：甲基化、移动元件和混合基因组不稳定性的研究

• 批准号: 0093250
• 负责人: Rachel O'Neill
• 金额: $ 64.5万
• 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: 2001
• 资助国家: 美国
• 起止时间: 2001-02-15 至 2007-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0093250&HistoricalAwards=false
• 关键词: CAREER; Investigations; Methylation; Mobile; Elements

Decades of genetic research have established the destructive influence endogenous mobile DNA elements have on genomes. Relatively little, however, has been learned about the strategies that have evolved to combat the disruptive influence of transposable elements. Disruptions in DNA methylation have been directly associated with activation of mobile elements, and it has been theorized that methylation's primary purpose is to keep mobile elements silent. We have observed a dramatic change in DNA methylation and consequent mobile element activation in hybrid marsupials. This observation suggests that, antithetical to their deleterious effects, transposable elements may confer genetic variability within populations. This project focuses on interspecific hybrids known to exhibit genomic instability, and investigates the breakdown of DNA methylation and the activity of mobile elements in the face of hybridization-induced genomic stress. Likewise, the genomic alterations observed in interspecific hybrids known to exhibit disruptions in methylation are being characterized more fully in order to ascertain the molecular mechanisms underlying genomic instability. These experiments promise to broaden our understanding of the mechanisms that maintain the integrity of karyotypes once they are fixed in a species. The molecular biological and cytogenetic techniques utilized in this study are uniquely suited for broadening the educational experience of molecular biology students at the University of Connecticut. An Applied Genomics Initiative in the department of Molecular and Cell Biology has been instigated with the primary goal of teaching students the latest conceptual and technical advances in functional genomics. As part of this CAREER project, new curricula is being developed that offers graduates, undergraduates, underprivileged secondary school students and continuing students from the private sector the opportunity to learn these topics. In newly designed lecture and laboratory courses, as well as in independent research projects, students learn about genome structure and the de-stabilizing influence of hybridization. Not only can students gain technical knowledge through hands-on experience at the bench, but also through observation and sample collection in the field.

几十年的遗传研究已经确定了内源性可移动DNA元件对基因组的破坏性影响。然而，人们对对抗转座因子的破坏性影响的策略却知之甚少。DNA甲基化的中断与可移动元件的激活直接相关，并且理论上甲基化的主要目的是保持可移动元件沉默。我们已经观察到DNA甲基化和随之的移动元件激活在杂交有袋动物的戏剧性变化。这一观察结果表明，与它们的有害作用相反，转座因子可能赋予种群内的遗传变异。本项目关注已知表现出基因组不稳定性的种间杂交，并研究DNA甲基化的破坏和面对杂交诱导的基因组胁迫时可移动元件的活性。同样，在已知表现出甲基化破坏的种间杂交中观察到的基因组改变正在被更充分地表征，以确定基因组不稳定性的分子机制。这些实验有望扩大我们对维持核型完整性机制的理解，一旦核型固定在一个物种中。本研究中使用的分子生物学和细胞遗传学技术特别适合于扩大康涅狄格大学分子生物学学生的教育经验。分子和细胞生物学系的应用基因组学计划已经启动，其主要目标是教授学生功能基因组学的最新概念和技术进展。作为这个职业项目的一部分，正在编制新的课程，为毕业生、本科生、贫困的中学生和私营部门的在读学生提供学习这些主题的机会。在新设计的讲座和实验课程以及独立研究项目中，学生将学习基因组结构和杂交的不稳定影响。学生不仅可以通过在实验台上的实践经验获得技术知识，还可以通过实地观察和样本收集获得技术知识。