CAREER: Bioelectric mechanisms of brain development

大脑的形成源于神经干细胞，通过一个被称为神经发生的过程，神经干细胞扩张并产生不同数量的神经元。神经发生的调控是至关重要的，因为增生缺陷会导致发育障碍和癌症。电解质平衡和生理pH值的维持对大脑的功能至关重要。pH调节蛋白突变导致人类神经发育障碍；然而，对于pH值的变化是如何调节大脑形成的，我们知之甚少。该项目利用果蝇来确定pH调节分子在神经发生过程中的作用。将利用尖端技术来发现pH值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。本科生将参加一门新的研究密集型课程，以确定影响大脑发育的电解质调节因子。与米苏拉的科学博物馆SpectrUM合作，将为K-12学生开发一个神经生物学和遗传学研究的展览。拟议的综合研究、教育和推广将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，从而增加在科学领域中代表性不足的学生的数量，包括来自印度裔美国人社区的学生。这项工作的主要目标是确定在脑形成过程中pH值的变化指导和促进神经发生的机制。以神经发生模型果蝇为研究对象，研究pH调节剂钠/质子交换剂和质子囊泡atp酶在神经干细胞不对称分裂和细胞身份中的作用。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，空间和时间控制的pH传感器将被用来解决动态的pH依赖方面的发展，这一直是难以捉摸的。本研究将发现通过pH动力学调节神经细胞谱系的分子机制。该项目由生物科学理事会IOS神经系统集群和美国国家科学基金会刺激竞争性研究的既定计划（EPSCoR）共同资助。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。

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.