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

“该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。“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靶点并在它们到达后在其上建立突触的能力。 Syndecan最近被证明是神经系统发育的重要调节剂。 Syndecan基因的突变导致果蝇胚胎在中枢神经系统中线的轴突引导中经常出现错误。 此外，Syndecan突变体在突触生长中具有严重缺陷。 Syndecan胞外结构域的结合伴侣最近已被确定，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Drosophila melanogaster进行生物化学和遗传筛选，以鉴定与Syndecan一起帮助建立中枢神经系统的新型蛋白质。 此外，将测试多种工程化的多配体蛋白聚糖表达构建体，以揭示多配体蛋白聚糖的哪些结构域是功能所需的。 这些研究将有助于深入了解Syndecan如何控制轴突导向和突触形成的分子机制，并可能发现控制这些过程的新基因。 此外，由于Syndecan从果蝇到人类都是高度保守的，因此该项目将提供有关神经元如何找到其突触靶点以及一旦接触突触后靶点突触如何生长的广泛适用信息。该项目将在一个小型文理学院进行，完全由本科生进行。 考虑从事科学职业的学生从本科研究经历中受益匪浅;它使他们能够了解科学知识是如何获得的，并考虑他们是否希望从事科学研究。 与PI密切合作，学生将开发自己的研究项目。 这项研究也被带入课堂，为本科生提供了额外的机会，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进行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和高中学生接触，将有更多的机会讨论研究和进行假设驱动的科学探究的过程。

"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.