NSF Postdoctoral Fellowship in Biology FY 2021: Elucidating the mechanism by which Taf14 links metabolic flux to gene transcription

该行动资助2021财年NSF生物学博士后研究奖学金，研究基因组，环境和表型之间相互作用的生命规则的综合研究。该奖学金支持将以创新方式为《生活规则》领域作出贡献的研究员的研究和培训。每一个生物都必须对周围的环境做出适当的反应。这是生物学的一个基本规则，无论你是酵母还是复杂的有机体，比如人类。对环境条件的不适当反应可能是致命的，因此，对这些反应的调节是至关重要的。调控是在基因水平上控制的，根据需要将正确的基因“打开”或“关闭”。生物体必须不断响应的一个关键环境因素是养分的可用性。该研究员将寻求理解营养供应与指定细胞生长的“开”和“关”基因之间的微妙关系。除了在此奖项中获得的科学进步外，该研究员还长期参与社区外展活动，特别是以青年为中心的活动，并将在该奖项的整个任期内继续向不同的受众开展外展活动。利用出芽酵母作为模式生物，这项研究将解决生物学中的一个基本问题：环境中的营养可用性如何转化为基因表达的变化，从而表明细胞是否应该继续生长和分裂。具体来说，这项研究将着眼于整个基因组中组蛋白修饰形式的表观遗传标记。研究表明，差异代谢的副产物沉积在组蛋白上，然后由组蛋白读取器结合，从而影响基因转录。组蛋白解读器Taf14最近被发现与促生长基因的调控有关。然而，Taf14与六种不同的基因调控复合物的关联掩盖了这种情况发生的确切机制。这项研究将对酵母菌进行基因工程改造，以选择性地破坏Taf14与每个复合体的相互作用，以便评估个体的贡献。该研究将通过展示代谢的不同副产物如何直接下游基因调控来推进科学知识。它将为表观遗传修饰如何转化为基因表达或抑制，从而影响细胞增殖提供有价值的培训和见解。根据该奖项，研究员还将积极参与北卡罗来纳大学的许多指导、教学和推广项目，特别是与北卡罗来纳公立学校系统直接相关的项目。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2021, Integrative Research Investigating the Rules of Life Governing Interactions Between Genomes, Environment and Phenotypes. The fellowship supports research and training of the Fellow that will contribute to the area of Rules of Life in innovative ways. Every living organism must respond appropriately to the environment around them. This is a fundamental rule in biology whether you are a yeast or complex organism such as a human. An inappropriate response to environmental conditions can be fatal, thus, the regulation of these responses is critical. Regulation is controlled at the genetic level turning the right genes “ON” or “OFF” as needed. One key environmental factor that organisms must continually respond to is nutrient availability. The Fellow will seek to understand the delicate relationship between nutrient availability and the “ON” and “OFF” genes that specify cellular growth. In addition to the scientific advancements gained during this award, the Fellow has a long track record of participating in community outreach events, especially youth-centered events, and will continue with outreach events to diverse audiences throughout the tenure of this award.Using budding yeast as a model organism, this research will address a fundamental question in biology: how nutrient availability in the environment is translated into changes in gene expression that signal whether cells should continue to grow and divide. Specifically, this research will look at epigenetic markers in the form of histone modifications across the genome. It has been shown that byproducts of differential metabolism are deposited on histones, which are then bound by histone readers that subsequently influence gene transcription. The histone reader, Taf14, has recently been connected to regulation of pro-growth genes. However, the exact mechanism through which this occurs is masked by Taf14’s association with six different gene regulatory complexes. This research will genetically engineer strains of yeast to selectively disrupt Taf14’s interaction with each complex so that individual contributions can be evaluated. The research will advance scientific knowledge by demonstrating how the different byproducts of metabolism direct downstream gene regulation. It will provide valuable training and insights into how epigenetic modifications are translated into gene expression or repression, thus influencing cell proliferation. Under this award, the Fellow will also actively engage in the many mentoring, teaching, and outreach programs available at the University of North Carolina, especially those directly involved with the North Carolina public school system.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.