Elucidating mechanistic connections between guidance signaling, microtubule regulation, and growth cone steering: Diversity Supplement

阐明引导信号传导、微管调节和生长锥转向之间的机制联系：多样性补充

• 批准号: 9671507
• 负责人: Laura Anne LOWERY
• 金额: $ 1.17万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-04 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9671507
• 关键词: Affect; Amino Acids; Behavior; Binding; Biochemical; Biology; Brain; Cues; Data; Development; Doctor of Philosophy; F-Actin; Female; Funding; Generations; Growth Cones; Hispanics; Mediating; Mentors; Mentorship; Microtubules; Modeling; Parents; Phosphorylation; Plus End of the Microtubule; Proteins; Regulation; Research; Research Personnel; Research Project Grants; Research Training; Senior Scientist; Series; Signal Pathway; Signal Transduction; Students; Swimming; TACC3 gene; Tadpoles; Techniques; Testing; Training; Work; Xenopus; biomedical scientist; career; insight; interest; neurodevelopment; neuronal growth; parent grant; programs; response; skills; training opportunity; undergraduate student; university student

Project Abstract It has long been established that growth cone navigation depends on regulated changes in both F-actin and microtubule (MT) dynamics in response to external guidance cues. However, the mechanisms by which these cues bring about specific changes in growth cone MT dynamics are a fundamental unresolved issue in the field. The parent research grant takes aim at that void, by investigating the functions of two interacting microtubule `plus-end tracking proteins' (+TIPs), TACC3 and XMAP215, and their regulatory mechanisms. These two +TIPs uniquely bind to the extreme end of the MT and their binding to MTs is thought to be regulated by phosphorylation. Our data support a model in which TACC3 and XMAP215 mediate changes in MT dynamics downstream of guidance cue signaling. We are currently funded to test the central mechanistic hypothesis that major guidance cue signaling pathways converge on TACC3 and XMAP215 to control MT plus-end dynamics and steer the growth cone. This supplement will fund the research training and career mentorship of a highly driven and enthusiastic first- generation female Hispanic undergraduate student, who has a strong interest and potential in eventually attending a graduate program in Biology. The undergraduate student will be trained not only in many diverse bench techniques, but she will be intensively mentored in how to be a successful biomedical scientist and succeed in a graduate PhD program in biology. With this supplement, she will work with a supportive team to make new insights into the mechanistic regulation of TACC3 during neural development, using a series of complementary approaches over the next three years. First, she will determine whether four critical phosphorylated amino acids are important for TACC3 biochemical interaction with XMAP215. Then, she will determine whether these amino acids affect the ability of TACC3 to bind to and regulate microtubules in neuronal growth cones. Finally, she will investigate whether these amino acids are important for TACC3 to promote normal swimming behaviors in Xenopus tadpoles as a readout of brain development. The undergraduate student will have extensive contact with her advisor as well as others on the parent grant (including a senior scientist, current PhD student, and senior undergraduate students). In the course of her undergraduate studies, she will have many opportunities to discuss and present her research in multiple forums, developing her skills not only as a bench biomedical researcher but as a scientific communicator. She will receive intensive mentoring from her advisor, and will participate in numerous additional training opportunities to strongly prepare her for the rigors of a graduate program.

项目摘要 长期以来，人们已经确定生长锥导航取决于两个方面的调节变化： F-肌动蛋白和微管 (MT) 动力学响应外部引导线索。然而， 这些线索导致生长锥 MT 动力学发生特定变化的机制 是该领域尚未解决的根本问题。家长研究补助金的目标是 void，通过研究两个相互作用的微管“正端跟踪蛋白”的功能 (+TIPs)、TACC3 和 XMAP215 及其调控机制。这两个+TIP 独一无二 结合到 MT 的最末端，并且它们与 MT 的结合被认为是受 磷酸化。我们的数据支持 TACC3 和 XMAP215 调节变化的模型 引导提示信号下游的 MT 动态。我们目前正在资助测试中央 主要指导信号信号通路汇聚于 TACC3 的机制假设 XMAP215 控制 MT 加端动态并引导生长锥。本补充将 资助高度驱动和热情的第一人的研究培训和职业指导 一代女西班牙裔本科生，对以下领域有浓厚的兴趣和潜力 最终参加了生物学研究生课程。本科生将接受培训 不仅在许多不同的卧推技巧上，而且她将在如何成为一名 成功的生物医学科学家并成功完成生物学研究生博士学位课程。有了这个 作为补充，她将与支持团队合作，对机制提出新的见解 使用一系列互补方法在神经发育过程中调节 TACC3 未来三年。首先，她将确定四个关键的磷酸化氨基是否 酸对于 TACC3 与 XMAP215 的生化相互作用很重要。那么，她将决定 这些氨基酸是否影响 TACC3 结合和调节微管的能力 神经元生长锥。最后，她将研究这些氨基酸是否对 TACC3 促进爪蟾蝌蚪正常游泳行为作为大脑读数 发展。本科生将与她的导师以及导师有广泛的联系 其他获得家长资助的人（包括高级科学家、现任博士生和高级科学家） 本科生）。在本科学习的过程中，她将会有很多 有机会在多个论坛上讨论和展示她的研究，从而发展她的技能 不仅作为一名替补生物医学研究员，而且作为一名科学传播者。她将收到 导师的强化指导，并将参加许多额外的培训 为她准备好应对研究生课程的严格要求的机会。