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）： 在这个修订后的应用程序中，我们建议桥接生物学和物理学的前沿课题，以创建肺部健康和疾病中集体细胞迁移的新物理图像。 该计划的项目和核心集中在一个共同的中心假设：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特性， 通过如在统一干扰相图上所述的玻璃化转变的概念将这些效应结合在一起。每个项目主任都是其各自学科的领导者。项目1（Weitz）将研究单文件迁移（1-D）中孤立（0-D）单个细胞水平的基本物理学，以及向2-D行为的过渡。这个项目将强调细胞体积调节在细胞堵塞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）中干扰的基本物理学。项目3（Drazen）将研究阻塞在支气管上皮中的作用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的新技术。核心B（韦斯）将寻找跨越项目和表征干扰相图区域的共同分子网络基序。核心C（Fredberg）是管理性的。总之，这个项目的跨学科项目和核心联合收割机将物理学和生物学结合在一起，这种结合很少实现。这些项目由一个中心假设统一起来，该假设是激进的、机械的和可检验的，并且有可能影响对肺损伤和修复的基本理解。