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

几十年的遗传学研究已经证实了内源性移动的DNA元件对基因组的破坏性影响。然而，相对较少的是，已经了解到的战略，已演变为打击破坏性的影响转座因子。DNA甲基化的破坏与移动的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移动的元件沉默。我们观察到杂交有袋类动物的DNA甲基化和随之而来的移动的元件激活的戏剧性变化。这一观察结果表明，与其有害作用相反，转座因子可能赋予种群内的遗传变异性。该项目的重点是已知表现出基因组不稳定性的种间杂交，并调查了DNA甲基化的分解和移动的元素在杂交诱导的基因组应激中的活性。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。这些实验有望拓宽我们对维持染色体组型完整性的机制的理解，一旦它们在一个物种中固定下来。在这项研究中使用的分子生物学和细胞遗传学技术是唯一适合扩大分子生物学学生在康涅狄格大学的教育经验。分子和细胞生物学系的应用基因组学计划已经启动，其主要目标是向学生传授功能基因组学的最新概念和技术进展。作为这一职业项目的一部分，正在制定新的课程，为毕业生、大学生、贫困中学生和私营部门的继续教育学生提供学习这些专题的机会。在新设计的讲座和实验室课程，以及在独立的研究项目中，学生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工作台上的实践经验获得技术知识，还可以通过实地观察和样品收集获得技术知识。

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.