Tools for mapping the tubulin landscape

绘制微管蛋白景观的工具

基本信息

批准号：
10785950
负责人：
Jeffrey Kyle Moore
金额：
$ 15.52万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-15 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10785950
关键词：
Amino Acid Sequence Antibodies Architecture Area Axon Binding Biochemical Brain Brain Diseases C-terminal Cells Chemicals Chimeric Proteins Code Cytoplasm Cytoskeleton Data Dendrites Development Disease Distal Elements Environment Exhibits Future Gene Family Goals Heterogeneity Human Genome Imaging Device Intrabody Kinesin Lead Malignant Neoplasms Maps Messenger RNA Microtubule-Associated Proteins Microtubules Modality Molecular Monoclonal Antibodies Morphogenesis Motor Movement Muscle Neurodevelopmental Disorder Neurons Nuclear Organelles Paclitaxel Pattern Pharmaceutical Preparations Play Population Positioning Attribute Post-Translational Protein Processing Process Recombinant Antibody Recombinants Refractory Regulation Research Research Personnel Role Signal Transduction Site Structural defect Surface Tail Testing Therapeutic Time Translations Tubulin Variant Visualization alpha Tubulin beta Tubulin brain malformation cancer cell cell motility cell type cost developmental disease dimer extracellular gain of function insight nerve supply programs recruit response success superresolution microscopy tool ubiquitin-protein ligase

项目摘要

Tools for mapping the tubulin landscape Project Summary: do Over information This tubulins. tubulin neuronal recombinant research whether new are essential to the architectural complexity and signaling efficiency of neurons. However, we not fully understand how neurons build specialized microtubule networks at the right place and right time. the past 15 years, we have come to appreciate that the tubulin subunits within microtubules carry in the form of posttranslational modifications that regulate the assembly and function of networks. proposal extends this concept to the level of the tubulin isotypes – the gene families that encode α - and β Our goal is to develop new tools that will enable the first-ever visualization and manipulation of a isotype in living cells. proposal will create tools that will advance our understanding of the β-tubulin isotype, TUBB3, during morphogenesis, but will also have broad impacts across many labs. Our approach will 1) create a form of the TUBB3-binding antibody Tuj1 that can be shared with other labs and bring down costs, 2) create the f irst-ever intrabody for studying a tubulin isotype in living ells, 3) determine TUBB3 exhibits biased enrichment to regions of the neuron or to microtubules with PTMs, 4) create a tool for rapid and selective depletion of TUBB3 in cells Microtubules - This c . The success of this proposal will set the stage for our future R01 proposal, which will elucidate the mechanisms that regulate TUBB3 localization and function during development, and how these are disrupted in disease.

绘制微管蛋白景观的工具项目概要：做超过信息这微管蛋白。微管蛋白神经元的重组的研究无论新的对于神经元的结构复杂性和信号传导效率至关重要。不完全了解神经元如何在正确的地点和正确的时间构建专门的微管网络。在过去的 15 年里，我们逐渐认识到微管内的微管蛋白亚基携带着以调节网络组装和功能的翻译后修饰的形式。提案将这一概念扩展到微管蛋白同种型的水平——编码 α 和 β 的基因家族我们的目标是开发新工具，首次实现对数据的可视化和操作活细胞中的同型。该提案将创建工具，以增进我们对 β-微管蛋白同种型 TUBB3 的理解，形态发生，但也会对许多实验室产生广泛的影响，我们的方法将 1) 创建一个 TUBB3 结合抗体 Tuj1 的形式，可以与其他实验室共享并降低成本，2) 创建第一个体内用于研究活体中的微管蛋白同种型，3) 确定 TUBB3 对神经元区域或具有 PTM 的微管表现出偏向富集，4) 创建快速选择性去除细胞中 TUBB3 的工具微管 - 这 c 该提案的成功将为我们未来的 R01 提案将阐明调节 TUBB3 定位和功能的机制在发育过程中，以及这些在疾病中如何被破坏。