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

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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.