Dissection of Signaling Networks Maintaining Metabolic Homeostasis

生物如何在食物供应显著的环境变化下维持代谢稳态的机制尚不完全清楚。该领域特别感兴趣的是对饥饿形成稳态反应的潜在机制。该研究项目将利用模式生物——黑腹果蝇（Drosophila melanogaster）的可追踪性，以及强大的分子和成像工具来解决有关代谢决策的基本问题。该建议的一个主要结果是加强对这些代谢网络保护的理解。初步结果表明，这些网络很可能是高度保守的，因此可以用于许多实际应用，从治疗到害虫管理。来自PI的初步数据支持了能量传感器，amp活化蛋白激酶（AMPK）调节脂肪动力学激素（AKH）的分泌的假设，该激素的功能是调动能量储存，并且是对营养限制的行为和生理反应所必需的。本项目将研究：1)激素信号在AKH细胞生理中的作用机制；激素信号系统与AMPK之间的联系；iii) AKH细胞兴奋性的调控机制。本提案中计划的实验将为特定细胞群体中的细胞信号提供新的信息，这是产生特定行为和生理变化以维持能量稳态所必需的。这个研究项目也将被用来作为一个工具，扩大本科生的研究机会，也为区域机构的教师。这些机会将为教师和学生层面的代表性不足的人群提供研究机会。这种研究和教育的无缝整合将产生广泛的影响，为各种各样的学生提供本科研究机会的好处。

The mechanisms of how organisms maintain metabolic homeostasis in light of significant environmental variation in food availability are not completely understood. Of particular interest of the field are the underlying mechanisms that form homeostatic responses to starvation. This research project will take advantage of the tractability of the model organism, Drosophila melanogaster and powerful molecular and imaging tools to address fundamental questions regarding metabolic decisions. One principal outcome of this proposal is to enhance understanding of the conservation of these metabolic networks. Preliminary results suggest that these networks are very likely to be highly conserved, and may therefore be leveraged for many practical applications, ranging from therapeutics to pest management. Preliminary data from the PI supports the hypothesis that the energy sensor, AMP-activated protein kinase (AMPK) regulates the secretion of Adipokinetic Hormone (AKH), which functions to mobilize energy stores and is required for behavioral and physiological responses to nutrient limitations. This project will investigate: i) Functional mechanisms of hormonal signaling on AKH cell physiology; ii) Connections between hormonal signaling systems and AMPK; and iii) Regulatory mechanisms of AKH cell excitability. The planned experiments in this proposal will contribute new information into the cellular signals within a defined cell population, which is required for generating specific behavioral and physiological changes to maintain energy homeostasis. This research project will also be used as a vehicle to extend undergraduate research opportunities to students, and also to faculty at regional institutions. These opportunities will provide research opportunities to underrepresented populations at both the faculty and student level. This seamless integration of research and education will have broad impacts, in providing the benefits of undergraduate research opportunities to a diversity of students.