RUI: Investigating the mechanisms of Syndecan function during nervous system development

RUI：研究 Syndecan 在神经系统发育过程中的功能机制

• 批准号: 0841551
• 负责人: Karl Johnson
• 金额: $ 51.99万
• 依托单位: Pomona College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0841551&HistoricalAwards=false
• 关键词: RUI; Investigating; mechanisms; Syndecan; function

"This award is funded under the American Recovery and Reinvestment Act of 2009(Public Law 111-5)."The proper development of the central nervous system depends on the ability of neurons to extend axons to their proper synaptic targets and to build synapses on them once they have arrived. Syndecan was recently shown to be a crucial regulator of nervous system development. Mutations in the Syndecan gene cause fruitfly embryos to develop with frequent errors in axon guidance at the midline of the central nervous system. In addition, Syndecan mutants have severe defects in synapse growth. Binding partners for the extracellular domain of Syndecan have recently been identified, however, the mechanisms by which Syndecan controls neural development is unknown. In this project, biochemical and genetic screens will be conducted using the fruitfly Drosophila melanogaster to identify novel proteins that work with Syndecan to help build the central nervous system. In addition, a variety of engineered Syndecan expression constructs will be tested in order to reveal which domains of Syndecan are required for function. These studies should provide insight into the molecular mechanisms of how Syndecan controls axon guidance and synapse formation, and also are likely to identify novel genes which control these processes. In addition, because Syndecan is highly conserved from Drosophila to humans, this project will provide broadly applicable information about how neurons find their synaptic targets, and how synapses grow once the postsynaptic target has been contacted. This project will be conducted at a small liberal arts college and entirely by undergraduate students. Students considering careers in science benefit tremendously from undergraduate research experiences; it allows them to learn how scientific knowledge is gained, and to consider whether they wish to pursue a career in scientific research. Working closely with the PI, students will develop their own research projects. The research is also brought into the classroom, providing additional opportunities for undergraduate students to use the mutants and other genetic materials developed in the PI's laboratory to conduct their own independent research projects in his upper-division courses. Lastly, contact with both junior high and high school students through the Cabrillo Marine Aquarium will allow additional opportunities to discuss research and the process of conducting hypothesis-driven scientific inquiry.

“该奖项是根据 2009 年美国复苏和再投资法案（公法 111-5）提供资金的。”中枢神经系统的正常发育取决于神经元将轴突延伸到适当的突触目标并在到达后在其上构建突触的能力。 Syndecan 最近被证明是神经系统发育的重要调节剂。 Syndecan 基因突变导致果蝇胚胎发育时中枢神经系统中线的轴突引导经常出现错误。 此外，Syndecan突变体在突触生长方面存在严重缺陷。 Syndecan 细胞外结构域的结合伴侣最近已被鉴定，然而，Syndecan 控制神经发育的机制尚不清楚。 在该项目中，将使用果蝇果蝇进行生化和遗传筛选，以确定与 Syndecan 一起帮助构建中枢神经系统的新型蛋白质。 此外，还将测试各种工程化 Syndecan 表达构建体，以揭示功能需要 Syndecan 的哪些结构域。 这些研究应该提供对 Syndecan 如何控制轴突引导和突触形成的分子机制的深入了解，并且还可能识别控制这些过程的新基因。 此外，由于 Syndecan 从果蝇到人类都高度保守，因此该项目将提供广泛适用的信息，了解神经元如何找到其突触目标，以及一旦接触到突触后目标，突触如何生长。该项目将在一所小型文理学院进行，完全由本科生进行。 考虑从事科学事业的学生可以从本科研究经历中受益匪浅；它使他们能够了解如何获得科学知识，并考虑他们是否希望从事科学研究事业。 学生将与 PI 密切合作，开发自己的研究项目。 该研究还被带入课堂，为本科生提供了额外的机会，让他们可以使用PI实验室开发的突变体和其他遗传材料，在他的高年级课程中开展自己的独立研究项目。 最后，通过卡布里洛海洋水族馆与初中生和高中生进行接触将为讨论研究和进行假设驱动的科学探究过程提供更多机会。