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

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。准确评估营养状况对生存至关重要。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。在脂肪因子过剩的状态下，脂肪因子释放一个信号，表明能量资源可以用于免疫和繁殖等昂贵的活动。在饥饿期间，它们的分泌减少，表明能量不足，从而导致能量节约。最近的证据表明，果蝇脂肪因子Upd2的核隔离是由at8控制的，at8是一种以自噬作用而闻名的蛋白质。此外，Upd2可以通过破坏Upd2和Atg8的蛋白质相互作用而被迫保持核，从而增加果蝇的饥饿抗性并促进饥饿后的饥饿反应。这些数据提示Upd2和Atg8可能影响基因表达。本研究旨在确定这种未经研究的脂肪因子驱动基因表达形式的作用。该项目将通过一个已建立的暑期实习项目，将这项研究用于教学和指导代表性不足的少数民族高中生，向学生传授基本的苍蝇研究概念，培养科学兴趣。该项目旨在描述Upd2和at8如何在营养胁迫期间和之后改变核景观来调节生物体适应性。这两种蛋白都不能结合DNA，因此与Upd2和Atg8相关的DNA/染色质结合蛋白将通过免疫沉淀来确定。该项目将使用表观基因组分析的CUT&amp；Tag方法确定Upd2与基因组结合的位置。同时，利用RNAseq可以生成与营养状态变化相关的基因的差异表达谱。两种分析的数据将结合使用当前的计算方法来确定Upd2以营养依赖的方式调节的候选基因。候选基因将在果蝇模型中突变，用于在喂食和饥饿条件下的摄食行为分析，以证明它们参与营养感知反应。这种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，研究员也将在这个研究系统中获得新的经验和训练。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. 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.