BRC-BIO:Glial regulation of neural homeostasis during environmental stress in D. melanogaster

我们周围的环境在不断变化，或大或小。生物系统必须利用过程来维持体内平衡（一种生理平衡），以便在波动的环境中继续发挥作用。神经元的电活动控制着生存所必需的基本身体功能和行为。在神经系统中，另一组细胞被称为神经胶质细胞，负责调节和支持神经元。PI和其他人最近的研究表明，神经胶质细胞在帮助神经元维持体内平衡方面发挥着重要作用。该项目将利用果蝇的遗传工具来阐明神经胶质和神经元如何相互作用的新机制，使动物能够在波动的环境中生存和茁壮成长。该项目将与包容性教育实践相结合，包括由PI的神经生物学实验室课程的本科生完成的实验，以及参与一项基于研究的指导计划，该计划面向来自STEM历史上代表性不足的群体的一年级本科生。该项目还将开发一个科学翻译项目，为非科学家创造资源，以英语以外的语言了解与社会相关的科学研究。总之，这项资助的目标是将不同群体的学生纳入研究动物应对压力的生物机制，让学生有机会在STEM中培养归属感，学习动手实验技能，并在会议和同行评审的出版物中展示他们的工作。虽然很多工作都集中在细胞内在和神经回路水平的机制上，神经元通过这些机制调节其兴奋性，但神经胶质调节神经系统对环境应激反应的机制却知之甚少。利用黑腹果蝇，PI实验室最近确定了神经桩鞘胶质（EGN）中电压门控钾通道癫痫和离子转运蛋白ncc69这两个基因在胶质内平衡中的作用。其他人已经证明EGN在成年黑腹龙中起吞噬细胞的作用，因此该项目验证了神经元的胶质吞噬作用的假设，在突触修剪等过程中，调节神经系统在应对环境压力时维持体内平衡的能力。此外，该项目将梳理发育和成人胶质功能对神经系统稳态的影响。最终，该项目利用丰富的遗传工具、神经生理和行为分析，揭示神经胶质功能在调节神经活动和动物行为中的基本原理。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。

The environment around us is constantly changing, in ways both big and small. Biological systems must utilize processes to maintain homeostasis (a physiological equilibrium) in order to continue functioning amidst a fluctuating environment. The electrical activity of neurons controls essential bodily functions and behaviors that are necessary for survival. Within the nervous system, another set of cells, called glia, regulate and support neurons. Recent work by the PI, and others, has shown that glial cells play important roles in helping neurons maintain homeostasis. This project will use genetic tools available in fruit flies to elucidate novel mechanisms for how glia and neurons interact to enable animals to survive and thrive in fluctuating environments. The project will be integrated with inclusive educational practices, including experiments completed by undergraduate students in the PI’s Neurobiology Lab Course, and participation in a research based mentoring program for first year undergraduates from historically underrepresented groups in STEM. This project will also develop a Science Translators Program, creating resources for non-scientists to learn about socially relevant science research, in languages other than English. Together, the objectives of this grant will incorporate a diverse group of students in studying biological mechanisms through which animals respond to stress, giving students opportunities to develop a sense of belonging in STEM, learn hands-on lab skills, and present their work at conferences and in peer-reviewed publications. While much work has focused on the cell intrinsic and neural circuit level mechanisms through which neurons regulate their excitability, mechanisms by which glia regulate the nervous system response to environmental stress are less well understood. Using Drosophila melanogaster, the PI’s lab has recently identified glial homeostatic roles for two genes, the voltage-gated potassium channel seizure and the ion transporter ncc69, in neuropile ensheathing glia (EGN). EGN have been shown by others to act as phagocytes in adult D. melanogaster, therefore this project tests the hypothesis that glial phagocytosis of neurons, in processes such as synaptic pruning, modulates the ability of the nervous system to maintain homeostasis in response to environmental stress. Furthermore, the project will tease apart the impact of developmental and adult glial function on nervous system homeostasis. Ultimately, the project takes advantage of the wealth of genetic tools, neurophysiological and behavioral assays available in D. melanogaster to uncover basic principles of glial function in their regulation of neural activity and animal behavior.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.