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.

脑形成是由神经元细胞通过称为神经发生的过程扩展和产生神经元种群的神经元细胞。神经发生的调节至关重要，因为增殖缺陷会导致发育障碍和癌症。电解质平衡和物理pH的维持对于功能性大脑至关重要。 pH调节蛋白的突变引起人类神经发育障碍。然而，关于pH的变化如何调节大脑形成的情况知之甚少。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。尖端技术将用于发现pH在大脑发育过程中如何影响神经元干细胞分裂。该研究计划与教育和外展计划紧密融合。本科生将参加新的研究密集型课程，以识别影响大脑发育的电解质调节器。将开发与米苏拉科学博物馆Spectrum合作的K-12学生展览。通过提供资源和技能来确保在广泛的生物科学职业道路上取得成功，这项工作的主要目标是确定pH指导和促进神经发生在大脑形成期间的神经发生的机制，从而促进科学领域的人数不足的学生，包括来自印度裔美国人社区的学生，包括来自印度裔美国人社区的人，包括来自印度裔美国人社区的学生，包括来自印度裔美国人社区的学生，包括来自印度裔美国人社区的学生，包括来自印度裔美国人社区的学生，包括来自印度裔美国人社区的学生，包括来自印度裔美国人社区的学生，包括来自印度裔美国人社区的人数不足的学生的组合变化。使用果蝇Melanogaster（一种具有良好特征的神经发生模型），将确定神经元干细胞不对称分裂和细胞身份中pH调节剂钠/质子交换器和质子囊泡ATPase的作用。这项投资将利用和开发尖端的遗传工具和创新方法来表征神经元发育过程中pH调节蛋白的细胞和亚细胞定位。此外，将采用空间和临时控制的pH传感器来解决以前难以捉摸的发展的动态pH依赖性方面。这项投资将发现通过pH动力学对神经细胞谱系进行调节的分子机制。该项目由该项目共同资助了生物科学局iOS的神经系统集群和既定的竞争研究（EPSCOR）的既定竞争性研究（EPSCOR）的既定基金会，这反映了NSF的智力统计范围，这是NSF的智力传教士的支持，并刺激了竞争性研究（EPSCOR）。 标准。