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

“这项奖励是根据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其适当的突触目标，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关键调节剂。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突变体在突触生长方面存在严重缺陷。Syndecan细胞外结构域的结合伙伴最近已被确定，然而，Syndecan控制神经发育的机制尚不清楚。在这个项目中，将使用果蝇进行生化和遗传筛选，以识别与Syndecan一起帮助建立中枢神经系统的新蛋白质。此外，将测试各种工程Syndecan表达结构，以揭示Syndecan的哪些结构域是功能所必需的。这些研究将提供Syndecan如何控制轴突引导和突触形成的分子机制，也可能发现控制这些过程的新基因。此外，由于Syndecan从果蝇到人类都高度保守，该项目将提供广泛适用的信息，了解神经元如何找到它们的突触靶点，以及突触后靶点接触后突触如何生长。这个项目将在一所小型文理学院进行，全部由本科生进行。考虑从事科学职业的学生从本科研究经历中受益匪浅；它让他们学习如何获得科学知识，并考虑他们是否希望从事科学研究事业。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，利用PI实验室开发的突变体和其他遗传物质，在他的高年级课程中进行他们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，将为讨论研究和进行假设驱动的科学探究的过程提供额外的机会。

"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.