CAREER: Bioelectric mechanisms of brain development

职业：大脑发育的生物电机制

• 批准号: 2338239
• 负责人: Beverly Piggott
• 金额: $ 110万
• 依托单位: University of Montana
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-03-01 至 2029-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2338239&HistoricalAwards=false
• 关键词: CAREER; Bioelectric; mechanisms; brain; development

Brain formation arises from neural stem cells which expand and generate diverse populations of neurons through a process known as neurogenesis. The regulation of neurogenesis is vital as proliferation defects cause developmental disorders and cancer. Electrolyte balance and the maintenance of physiological pH are essential for a functional brain. Mutations in pH regulatory proteins cause neurodevelopmental disorders in humans; yet remarkably little is known about how changes in pH regulate brain formation. This project uses the fruit fly to determine the role of pH regulatory molecules during neurogenesis. Cutting-edge techniques will be utilized to discover how pH influences neural stem cell division during brain development. The research plan is tightly integrated with educational and outreach initiatives. Undergraduates will participate in a new research-intensive course identifying electrolyte regulators affecting brain development. Collaborating with Missoula’s science museum, SpectrUM, an exhibit for K-12 students in neurobiology and genetics research will be developed. The combined research, education and outreach proposed will boost numbers of underrepresented students, including those from Indian American communities, in science by providing resources and skills to ensure success in a wide range of biological sciences career paths.The major goal of this work is to identify the mechanisms by which changes in pH instruct and facilitate neurogenesis during brain formation. Using Drosophila melanogaster, a well characterized model for neurogenesis, the role of pH regulators sodium/proton exchangers and proton vesicular ATPase in neural stem cell asymmetric division and cell identity will be determined. This investigation will leverage and develop cutting-edge genetic tools and innovative approaches to characterize cellular and subcellular localization of pH regulatory proteins during neural development. In addition, spatially and temporally controlled pH sensors will be employed to resolve dynamic pH-dependent aspects of development that have remained previously elusive. This investigation will discover the molecular mechanisms underlying regulation of neural cell lineage by pH dynamics.This project is jointly funded by the Neural Systems Cluster in IOS of the Directorate for Biological Sciences and the Established Program to Stimulate Competitive Research (EPSCoR) of the National Science Foundation.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.

脑的形成源于神经干细胞，其通过称为神经发生的过程扩展并产生不同的神经元群体。神经发生的调节是至关重要的，因为增殖缺陷会导致发育障碍和癌症。电解质平衡和生理pH值的维持对功能性大脑至关重要。pH调节蛋白的突变会导致人类神经发育障碍;然而，人们对pH值的变化如何调节大脑形成知之甚少。该项目使用果蝇来确定pH调节分子在神经发生过程中的作用。尖端技术将被用来发现pH如何影响大脑发育过程中的神经干细胞分裂。研究计划与教育和推广活动紧密结合。本科生将参加一个新的研究密集型课程，确定影响大脑发育的电解质调节剂。与米苏拉的科学博物馆，光谱，为K-12学生在神经生物学和遗传学研究的展览将开发合作。联合研究，教育和推广建议将提高代表性不足的学生，包括那些来自印度裔美国人社区，在科学提供资源和技能，以确保在广泛的生物科学职业道路的成功。这项工作的主要目标是确定的机制，通过pH值的变化指示和促进大脑形成过程中的神经发生。使用果蝇，一个很好的表征模型神经发生，pH调节剂钠/质子交换和质子囊泡ATP酶在神经干细胞不对称分裂和细胞身份的作用将被确定。这项研究将利用和开发尖端的遗传工具和创新方法来表征神经发育过程中pH调节蛋白的细胞和亚细胞定位。此外，将采用空间和时间控制的pH传感器来解决以前仍然难以捉摸的动态pH依赖性方面的发展。本研究旨在揭示pH动力学调控神经细胞谱系的分子机制。本项目由生物科学理事会IOS神经系统组和刺激竞争研究计划（EPSCoR）共同资助。该奖项反映了NSF的法定使命，并被认为是值得通过使用该基金会的知识产权进行评估的支持。优点和更广泛的影响审查标准。