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

在过去的六十年里，科学在我们对遗传学在决定生物体结构和功能中的作用的理解上取得了令人难以置信的进步，这对我们治疗疾病、改善农业资源和保护自然人口和社区的能力具有重要的影响。然而，即使是相同的基因，也可能根据有机体生长和生活的环境而产生非常不同的影响，当暴露在环境压力下时，会对身体特征产生终生甚至数代的影响。这些变化是如何在分子水平上完成的，尽管对身体成功适应急性和慢性应激条件至关重要，但人们对此知之甚少。在这个项目中，研究人员将研究果蝇以及生活在不同环境中的密切相关物种对压力温度的表观遗传反应，以此作为揭示细胞检测和响应环境压力的分子机制的模型。这项工作将为不同的研究生和本科生提供尖端基因组测序技术和生物信息学分析方面的研究和培训机会，并将STEM推广到三个EPSCoR司法管辖区(佛蒙特州、罗德岛州和肯塔基州)服务不足的城市和农村社区的高中生。此外，作为该项目的一部分，五名新的教职员工将得到指导。技术描述在该项目中，来自VT、RI和KY的研究人员团队将合作测试这一假设，即表观遗传调节因子在环境传感器和蛋白质生产之间扮演中介角色，在染色质可及水平上改变可用于转录的基因集，然后通过表位转录分子的作用微调表达。主要目的是确定：1)表观遗传机制是否以及如何调节热耐性中的可塑性变化；2)表观遗传变异在多大程度上支持表型可塑性的自然分离变异；以及3)表观遗传差异在进化过程中在适应能力转移中的作用。为了确定驱动可塑性的表观遗传机制，该项目组将表征与发育适应、成虫可逆适应以及对高温和低温反应的快速硬化相关的染色质可及性、翻译后组蛋白修饰、miRNA和lncRNA的变化。功能性遗传操作将用于验证候选的因果表观遗传机制。将采用全基因组关联作图和实验进化方法来评估热塑性的遗传结构。最后，为了测试生态位向更冷或更暖的栖息地的转变是否伴随着这些塑料反应的进化得失，研究人员将重建新大陆果蝇物种热塑性能力进化转变的历史。该项目将建立比较和实验模型，以了解热塑性的进化史和分子机制，这些模型非常适合于解决有关可塑性驱动因素的长期假设，并调查可塑性在促进生物在面对快速、渐进的气候变化时的弹性方面的生态和进化作用。这个项目将涉及五名具有不同专业领域的初级教员。两名初级教员主要来自本科院校(PUI)，针对这些初级教员的指导计划已经到位。三名博士后研究助理将参与该项目，他们将熟悉PUI和博士授予机构的教职员工的经验。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.