Dissection of Signaling Networks Maintaining Metabolic Homeostasis

鉴于食物供应方面的重大环境变化，生物体如何维持代谢动态平衡的机制尚未完全了解。该领域特别感兴趣的是形成对饥饿的动态平衡反应的潜在机制。这项研究项目将利用模式生物--黑腹果蝇的易操纵性，以及强大的分子和成像工具来解决有关代谢决定的基本问题。这项提议的一个主要结果是加强了对这些代谢网络的保护的理解。初步结果表明，这些网络非常可能是高度保守的，因此可能被用于许多实际应用，从治疗到虫害管理。来自PI的初步数据支持这样的假设，即能量感受器AMP激活的蛋白激酶(AMPK)调节脂肪动力激素(AKH)的分泌，AKH具有动员能量储存的功能，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；2)激素信号系统与AMPK之间的联系；3)AKH细胞兴奋性的调节机制。这项计划中的实验将为特定细胞群体内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平衡所必需的。该研究项目还将被用作一种工具，将本科生的研究机会扩大到学生和地区机构的教职员工。这些机会将为教师和学生层面上代表性不足的人群提供研究机会。这种研究和教育的无缝结合将产生广泛的影响，为不同类型的学生提供本科生研究机会的好处。

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.