CAREER: Bioelectric mechanisms of brain development

脑的形成来自神经干细胞，神经干细胞通过一个被称为神经发生的过程扩张并产生不同数量的神经元。神经发生的调控至关重要，因为增殖缺陷会导致发育障碍和癌症。电解质平衡和维持生理pH值对大脑的功能至关重要。PH调节蛋白的突变会导致人类的神经发育障碍；然而，人们对pH的变化如何调节大脑形成知之甚少。这个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。将利用尖端技术来发现在大脑发育过程中pH如何影响神经干细胞分裂。研究计划与教育和推广活动紧密结合在一起。本科生将参加一门新的密集研究课程，确定电解质调节剂对大脑发育的影响。与米苏拉科学博物馆SPECTRUM合作，将为K-12学生开发神经生物学和遗传学研究的展览。拟议的研究、教育和推广相结合，将通过提供资源和技能，确保在广泛的生物科学职业道路上取得成功，增加科学领域中代表性不足的学生的数量。这项工作的主要目标是确定在大脑形成过程中，PH值变化指导和促进神经发生的机制。利用果蝇，一个很好地描述神经发生的模型，将确定pH调节器，钠/质子交换器和质子囊泡ATPase在神经干细胞不对称分裂和细胞特性中的作用。这项研究将利用和开发尖端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以前仍然难以捉摸的动态与pH有关的发育方面。这项研究将发现pH动态调节神经细胞谱系的分子机制。该项目由生物科学局iOS的神经系统集群和国家科学基金会建立的刺激竞争研究计划(EPSCoR)联合资助。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。

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.