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

BRC-BIO：环境应激期间神经胶质对黑腹果蝇神经稳态的调节

• 批准号: 2216837
• 负责人: Alexis Hill
• 金额: $ 44.54万
• 依托单位: College of the Holy Cross
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2216837&HistoricalAwards=false
• 关键词: BRC; BIO; Glial; regulation; neural

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.

我们周围的环境不断发生着大大小小的变化。生物系统必须利用过程来维持稳态（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生存所需的基本身体功能和行为。在神经系统内，另一组细胞（称为神经胶质细胞）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稳态方面发挥着重要作用。该项目将利用果蝇中可用的遗传工具来阐明神经胶质细胞和神经元如何相互作用的新机制，以使动物能够在波动的环境中生存和繁衍。该项目将与包容性教育实践相结合，包括本科生在 PI 神经生物学实验室课程中完成的实验，以及参与针对 STEM 历史上代表性不足群体的一年级本科生的研究型指导计划。该项目还将开发一个科学翻译计划，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，这笔赠款的目标将让不同的学生群体参与研究动物应对压力的生物机制，让学生有机会培养 STEM 的归属感，学习实验室实践技能，并在会议和同行评审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其兴奋性的细胞内在和神经回路水平机制上，但神经胶质细胞调节神经系统对环境应激反应的机制尚不清楚。 PI 的实验室最近利用果蝇确定了神经胶质鞘神经胶质细胞 (EGN) 中两个基因的神经胶质稳态作用，即电压门控钾通道癫痫和离子转运蛋白 ncc69。其他人已证明 EGN 在成年黑腹果蝇中充当吞噬细胞，因此该项目测试了这样的假设：在突触修剪等过程中，神经胶质细胞的吞噬作用调节神经系统响应环境压力而维持稳态的能力。此外，该项目将梳理发育和成人神经胶质功能对神经系统稳态的影响。最终，该项目利用黑腹果蝇中丰富的遗传工具、神经生理学和行为测定来揭示神经胶质功能在神经活动和动物行为调节中的基本原理。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。