RII Track-2 FEC: From Genome to Phenome in a Stressful World: Epigenetic Regulatory Mechanisms Mediating Thermal Plasticity in Drosophila

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Non-technical descriptionOver the last sixty years, science has made incredible advances in our understanding of the role of genetics in determining the structure and function of living organisms, with important implications for our ability to treat disease, improve agricultural resources, and conserve natural populations and communities. Yet even the same genes can have very different effects depending on the environment in which an organism develops and lives, with life-long or even multigenerational effects on physical traits when exposed to environmental stress. How these changes are accomplished at the molecular level is poorly understood, despite being critical for successful adjustment of the body to acute and chronic stress conditions. In this project, the researchers will investigate the epigenetic response to stressful temperatures in the fruit fly Drosophila melanogaster, along with closely related species living in diverse environments, as a model for uncovering the molecular mechanisms by which cells detect and respond to environmental stress. This work will provide research and training opportunities for a diverse group of graduate and undergraduate students in cutting-edge genomic sequencing technologies and bioinformatic analysis, with STEM outreach to high-school students from under-served urban and rural communities in three EPSCoR jurisdictions (Vermont, Rhode Island, and Kentucky). In addition, five new faculty members will be mentored as part of this project.Technical descriptionIn this project, a team of researchers from VT, RI, and KY will work collaboratively to test the hypothesis that epigenetic regulators act as an intermediary between environmental sensors and protein production, altering the set of genes available for transcription at the level of chromatin accessibility and then fine-tuning expression through the action of epitranscriptomic molecules. The primary objectives are to determine: 1) whether and how epigenetic mechanisms mediate plastic changes in thermal tolerance; 2) the extent to which epigenetic variation underlies natural segregating variation in phenotypic plasticity; and 3) the role of epigenetic divergence in shifting capacity for acclimation over evolutionary time. To identify epigenetic mechanisms driving plasticity, the project team will characterize changes in chromatin accessibility, post-translational histone modification, miRNA and lncRNA associated with developmental acclimation, adult-reversible acclimation, and rapid hardening in response to high and low temperatures in Drosophila melanogaster. Functional genetic manipulations will be used to validate candidate causal epigenetic mechanisms. Genome-wide association mapping and experimental evolution approaches will be employed to evaluate the genetic architecture of thermal plasticity. Finally, to test whether niche transitions to colder or warmer habitats are accompanied by evolutionary gains or losses of these plastic responses, the researchers will reconstruct the history of evolutionary shifts in capacity for thermal plasticity in species across New World species of Drosophila. The project will establish comparative and experimental models for understanding the evolutionary history and molecular mechanisms of thermal plasticity that are ideally suited to address long-standing hypotheses concerning the drivers of plasticity, and investigate the ecological and evolutionary role of plasticity in promoting organismal resilience in the face of rapid, progressive shifts in climate. This project will involve five junior faculty members with different areas of expertise. Two junior faculty members are from Primarily Undergraduate Institutions (PUIs), and mentoring programs that target these junior faculty members are in place. Three post-doctoral research associates will be involved in the project, who will become familiar with the experiences of faculty members at both PUIs and PhD granting institutions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.