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，变化的方式有大有小。生物系统必须利用各种过程来维持动态平衡(生理平衡)，以便在不断变化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。在神经系统内，另一组细胞，称为神经胶质，负责调节和支持神经元。PI和其他人最近的工作表明，神经胶质细胞在帮助神经元维持内稳态方面发挥着重要作用。这个项目将使用果蝇中可用的遗传工具来阐明胶质细胞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，以及参与一项针对STEM历史上代表性不足群体的一年级本科生的基于研究的指导计划。该项目还将开发一个科学翻译者计划，为非科学家创造资源，以英语以外的语言学习与社会相关的科学研究。总而言之，这笔资助的目标将包括不同群体的学生，研究动物对压力做出反应的生物机制，让学生有机会在STEM中培养归属感，学习动手实验室技能，并在会议和同行评议的出版物上展示他们的工作。虽然许多工作都集中在神经元调节兴奋性的细胞固有和神经回路水平的机制上，但对神经胶质细胞调节神经系统对环境应激的反应的机制了解较少。利用黑腹果蝇，PI的实验室最近确定了两个基因--电压门控钾通道癫痫和离子转运体ncc69--在神经丛生神经胶质细胞(EGN)中的胶质细胞内稳态作用。其他人已经证明Egn在成年黑腹果蝇身上扮演着吞噬细胞的角色，因此这个项目测试了神经元的胶质吞噬作用，在突触修剪等过程中，调节神经系统在应对环境压力时保持内稳态的能力的假说。此外，该项目将梳理出发育和成人神经胶质功能对神经系统动态平衡的影响。最终，该项目利用D.Blackogaster提供的丰富的遗传工具、神经生理和行为分析来揭示神经活动和动物行为调节中神经胶质功能的基本原理。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。

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.