Physics of collective cellular migration in lung health and disease

肺部健康和疾病中集体细胞迁移的物理学

• 批准号: 8898898
• 负责人: Jeffrey J Fredberg
• 金额: $ 243.23万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8898898
• 关键词: 3-Dimensional; Asthma; Behavior; Biological; Biology; Bronchial Spasm; CREB1 gene; Candidate Disease Gene; Cell Volumes; Cells; D Cells; Discipline; Disease; Epithelial Cells; Genomics; Glass; Health; Human; Image; Imaging technology; Laboratories; Lung; Lung diseases; MDCK cell; Mechanics; Methodology; Methods; Molecular; Pathogenesis; Phase; Phenotype; Physics; Process; Regulation; Role; Signal Pathway; Stress; System; Wound Healing; activating transcription factor 3; airway epithelium; asthmatic; bronchial epithelium; cell motility; lung injury; lung repair; migration; monolayer; new technology; novel; programs; response; transmission process

DESCRIPTION (Provided by applicant): In this revised application we propose to bridge cutting-edge topics in biology and physics in order to create a new physical picture of collective cellular migration in lung health and disease. The projects and cores of this program focus upon a common central hypothesis: In collective behaviors of epithelial cells in the lung, di- verse physical factors and their multiple biological effects are brought together by the concept of the glass transition as described on a unifying jamming phase diagram. Each project director is a leader in his or her respective discipline. Project 1 (Weitz) will investigate basic physics at the level of the single cell in isolation (0-D) in single-file migration (1-D), and in transition to 2-D behavior. This project will emphasize the unifying role of cell volume regulation in mechanical determinants of cell jamming. Project 2 (Fredberg) will investigate basic physics of jamming in monolayers (2-D) and cell clusters (3-D). Project 3 (Drazen) will investigate the role of jamming in the bronchial epithelium as a basic mechanisms of asthma pathogenesis. Core A (Butler, Zaman, Krishnan) will support and develop novel technologies for imaging of physical forces. Core B (Weiss) will seek common molecular network motifs that span projects and characterize regions of the jamming phase diagram. Core C (Fredberg) is administrative. Together, the interdisciplinary projects and cores of this pro- gram project combine physics and biology at a level that is realized only rarely. The projects are unified by a central hypothesis that is radical, mechanistic and testable, and that has the potential to impact basic under- standing of lung injury and repair.

描述(由申请人提供)： 在这一修订的应用中，我们建议将生物学和物理学的前沿主题联系起来，以创建一幅关于肺部健康和疾病中集体细胞迁移的新的物理图景。 该计划的项目和核心集中在一个共同的中心假设上：在肺上皮细胞的集体行为中，不同的物理因素及其多种生物学因素 通过统一干扰相图上描述的玻璃化转变的概念，将效果结合在一起。每个项目主管都是他或她各自学科领域的领导者。项目1(Weitz)将在单文件迁移(1-D)和过渡到2-D行为的隔离(0-D)的单细胞水平上研究基本物理。这个项目将强调细胞体积调节在细胞干扰的机械决定因素中的统一作用。项目2(Fredberg)将研究单层(2-D)和细胞团(3-D)中干扰的基本物理。项目3(DRAZEN)将调查作为哮喘发病基本机制的支气管上皮堵塞的作用。核心A(巴特勒、扎曼、克里希南)将支持和开发物理力量成像的新技术。核心B(Weiss)将寻找跨越项目和表征干扰相图区域的共同分子网络基元。核心C(Fredberg)是行政管理部门。总而言之，这个项目的跨学科项目和核心将物理学和生物学结合在一起，达到了很少有人实现的水平。这些项目统一于一个中心假设，该假设是激进的、机械性的和可测试的，并有可能影响对肺损伤和修复的基本理解。