Development and function in mucociliary epithelia

粘液纤毛上皮的发育和功能

基本信息

批准号：
10658656
负责人：
John B Wallingford
金额：
$ 39.75万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-15 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10658656
关键词：
Active Biological Transport Address Airway Disease Architecture Automobile Driving Award Biological Biological Process Biology Carrier Proteins Cell physiology Cells Cellular biology Cilia Cytoplasm Cytoplasmic Organelle Data Data Set Defect Development Diffusion Disparate Distal Dynein ATPase Elements Epithelium Etiology Eukaryota Failure Genetic Genetic Diseases Goals Human Human Genetics Inhalation Left Light Link Lung Lung diseases Maps Methods Molecular Molecular Biology Molecular Chaperones Morphogenesis Motor Movement Mucous body substance Organelles Orthologous Gene Pathologic Pathology Patients Pattern Physiology Play Process Proteins Proteomics Radial Resolution Role Sales Site System Tissues Work Xenopus base cell motility ciliopathy cilium motility experimental study improved in vivo innovation interdisciplinary approach mucus clearance novel protein protein interaction regenerative therapy repaired

项目摘要

Abstract: The mucociliary epithelium plays a key role in both normal and pathological airway biology, as it provides the first line of defense against inhaled agents. Defects in ciliary beating in multiciliated cells (MCCs) in the airway contribute to the progression of both genetic and acquired airway diseases. Here, we will study the molecular mechanisms controlling development and function of MCCs. The motor proteins that drive ciliary beating are assembled in the cytoplasm, and under the previous version of this award, we discovered a novel organelle in which these motors are concentrated with various factors that direct their assembly. The first Aim of this project will explore the hierarchy of interaction among proteins in these novel organelles; the second will explore the mechanisms by which motors are transported into cilia, and the third will use large-sale proteomic approaches to identify novel protein-protein interactions important for motor assembly and function. By rapidly determining the functions of several new protein involved in distinct processes in MCC development, the Aims in this proposal will provide critical new depth to our understanding of these essential cell. Moreover, by linking these the disparate processes in MCCs, the experiments here will add crucial new breadth to our understanding as well. Impact: Experiments proposed here will lead to a more detailed understanding of the cell biology and genetics of MCCs and ciliary beating. The results will aid in the development of regenerative therapies aimed at repairing or restoring damaged tissue and improving mucus clearance in patients with airway disease.

抽象的：粘膜钙上皮在正常和病理气道生物学中都起着关键作用，因为它提供了对吸入特工的第一道防线。气道多纤毛细胞（MCC）中睫状跳动的缺陷有助于遗传和获得气道疾病的进展。在这里，我们将研究控制MCC发展和功能的分子机制。电动机驱动睫状跳动的蛋白质在细胞质中组装，并在此之前的先前版本下组装奖项，我们发现了一个新颖的细胞器，其中这些电动机集中在各种因素中他们的组装。该项目的第一个目的将探讨这些项目之间蛋白质之间相互作用的层次结构新颖的细胞器；第二个将探索电动机运输到纤毛的机制，然后第三将使用大型蛋白质组学方法来识别对运动很重要的新型蛋白质 - 蛋白质相互作用组装和功能。通过快速确定与独特的几种新蛋白的功能 MCC开发过程中的过程，该提案的目标将为我们的理解提供关键的新深度这些必需的细胞。此外，通过将这些不同的过程链接在MCC中，此处的实验将也为我们的理解添加至关重要的新广度。影响：此处提出的实验将导致对细胞生物学和遗传学的更详细的了解 MCC和睫毛跳动。结果将有助于开发针对的再生疗法修复或恢复组织疾病患者的组织受损的组织并改善粘液清除率。