NSF Postdoctoral Fellowship in Biology FY 2021: Deciphering how adipokine control of the epigenome impacts an organism's starvation response

这一行动为NSF 2021财年生物学博士后研究奖学金提供了资金，综合研究调查了支配基因组、环境和表型之间相互作用的生命规则。该奖学金支持研究员的研究和培训，这些研究员将以创新的方式为生活规则领域做出贡献。对营养状况的准确评估对生存至关重要。脂肪细胞通过分泌一种叫做脂肪因子的激素来发出营养过剩的信号。脂肪因子调节几个生理过程的决定，包括饥饿、免疫和生殖。在过剩的状态下，脂肪因子释放出一种信号，表明能源资源可以用于昂贵的活动，如免疫和生殖。在饥饿期间，它们的分泌减少，表明能量不足，推动能源节约。最近的证据表明，果蝇脂肪因子Upd2的核隔离受Atg8控制，Atg8是一种以其在自噬中的作用而闻名的蛋白质。此外，Upd2可以通过破坏Upd2和Atg8的蛋白质-蛋白质相互作用而被迫保持核状态，从而增强果蝇的抗饥饿性，并促进饥饿后的饥饿反应。这些数据表明，Upd2和Atg8可能影响基因表达。这项研究试图确定这种未被研究的脂肪因子驱动的基因表达形式的作用。该项目将致力于这项研究，通过一个既定的暑期实习计划来教授和指导未被充分代表的少数民族的高中生，向学生传授基本的苍蝇研究概念并培养科学兴趣。该项目试图描绘出Upd2和Atg8如何在营养应激期间和之后改变核景观来调节身体健康。这两种蛋白都不能与DNA结合，因此与Upd2和Atg8相关的DNA/染色质结合蛋白将通过免疫沉淀法测定。该项目将使用表观基因组图谱的切割和标签方法来确定Upd2与基因组的结合位置。结合起来，将使用RNAseq生成与营养状态变化相关的基因的差异表达谱。来自这两个分析的数据将使用当前的计算方法结合起来，以确定受Upd2以依赖于营养的方式调控的候选基因。在果蝇模型中，候选基因将发生突变，用于分析摄食和饥饿条件下的取食行为，以证明它们参与了营养感知反应。这一行为筛选将提供一种有趣而简单的方式向本科生介绍苍蝇研究的基本概念，该研究员还将在该研究系统中获得新的经验和培训。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。

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. An accurate assessment of nutritional status is essential for survival. Fat cells signal a nutrient surplus state by secreting hormones called adipokines. Adipokines regulate decisions on several physiological processes including hunger, immunity, and reproduction. In surplus states, adipokines release a signal indicating energy resources can be devoted to costly activities like immunity and reproduction. During starvation, their secretion is reduced, signaling an energy deficit driving energy conservation. Recent evidence suggests that nuclear sequestration of the fly adipokine Upd2 is controlled by Atg8, a protein known for its role in autophagy. Furthermore, Upd2 can be forced to remain nuclear by disrupting the protein-protein interactions of Upd2 and Atg8, resulting in increased starvation resistance and promoting post-starvation hunger responses in flies. These data suggest that Upd2 and Atg8 may affect gene expression. This study seeks to determine the role of this unstudied form of adipokine-driven gene expression. The project will devote this research to teaching and mentoring high school students of underrepresented minorities through an established summer internship program to teach students basic fly research concepts and cultivate scientific interest.The project seeks to delineate how Upd2 and Atg8 modify the nuclear landscape to regulate organismal fitness during and after nutrient stress. Neither protein can bind DNA, so DNA/Chromatin binding proteins associated with Upd2 and Atg8 will be determined via immunoprecipitation. The project will determine where Upd2 binds to the genome using the CUT&Tag method of epigenomic profiling. In conjuction, a differential expression profile of genes associated with changes in nutrient state will be generated using RNAseq. Data from both analyses will be combined using current computational approaches to identify candidate genes regulated by Upd2 in a nutrient-dependent manner. Candidate genes will be mutated in the fly model for feeding behavior analysis during fed and starvation conditions to prove their involvement in the nutrient sensing response. This behavioral screening will provide a fun and simple way to introduce undergraduates to basic concepts of fly research and the Fellow will receive new experience and training in this study system as well.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.