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: 9086401
• 负责人: Jeffrey J Fredberg
• 金额: $ 243.94万
• 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/9086401
• 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）： 在这个修订后的应用程序中，我们建议将生物学和物理学的前沿主题联系起来，以创建肺部健康和疾病中集体细胞迁移的新物理图景。 该项目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因素 正如统一干扰相图上所描述的，玻璃化转变的概念将效应汇集在一起​​。每个项目总监都是其各自学科的领导者。项目 1 (Weitz) 将研究单细胞迁移 (1-D) 中孤立 (0-D) 水平的基础物理，以及向 2-D 行为转变的过程。该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）和细胞簇（3-D）干扰的基本物理原理。项目 3（Drazen）将研究支气管上皮细胞中的干扰作为哮喘发病机制的基本机制。核心 A（Butler、Zaman、Krishnan）将支持和开发物理力成像新技术。 Core B (Weiss) 将寻找跨越项目并表征干扰相图区域的常见分子网络图案。核心 C (Fredberg) 是行政性的。该计划项目的跨学科项目和核心将物理学和生物学结合在一起，达到了很少实现的水平。这些项目由一个激进的、机械的和可测试的中心假设统一起来，并且有可能影响对肺损伤和修复的基本理解。