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.

映射小管蛋白景观的工具项目摘要：做超过信息这小管。微管蛋白神经元重组研究无论新的对于神经元的建筑复杂性和信号传导效率至关重要。但是，我们不完全了解神经元如何在正确的位置和正确的时间建立专门的微管网络。在过去的15年中，我们已经意识到微管内的微管蛋白亚基携带以调节网络组装和功能的翻译后修饰的形式。提案将此概念扩展到微管蛋白同种型水平 - 编码α-和β的基因家族我们的目标是开发新工具，以实现有史以来的第一个可视化和操纵活细胞中的同种型。提案将创建工具，以提高我们对β-微管蛋白同种型TUBB3的理解形态发生，但也将对许多实验室产生广泛的影响。我们的方法将1）创建一个可以与其他实验室共享的TUBB3结合抗体TUJ1的形式成本，2）创建有史以来研究小管蛋白同种型中的第一个f irt-fribogy，3）确定 TUBB3表现出对神经元区域或PTMS微管的偏见富集，4）创建一个快速和选择性部署TUBB3在细胞中的工具微管 - 这 c 。该提议的成功将为我们未来的R01提案，该提案将阐明调节TUBB3定位和功能的机制在发育期间，以及如何破坏疾病。