Mechanisms coordinating cell behaviors within tissues during development

发育过程中协调组织内细胞行为的机制

• 批准号: 10613921
• 负责人: Karen Kasza
• 金额: $ 38.92万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10613921
• 关键词: Address; Adhesives; Architecture; Award; Biochemical; Biological; Cells; Complex; Congenital Abnormality; Development; Disease; Drosophila melanogaster; Embryonic Development; Epithelium; Foundations; Genetic; Goals; Human; In Vitro; Individual; Malignant Neoplasms; Mechanics; Modeling; Molecular; Morphogenesis; Movement; Multicellular Process; Organ; Process; Proteins; Regulation; Research; Shapes; Structure; Techniques; Technology; Therapeutic; Tissues; Work; biological systems; cell behavior; fly; human disease; in vivo; innovation; insight; model organism; new technology; novel strategies; novel therapeutic intervention; programs; self organization; tool

PROJECT SUMMARY/ABSTRACT The formation of functional tissue architectures during embryonic development depends on the ability of cells to orchestrate collective tissue-level movements. The goal of my research program is to understand how cells work together to collectively generate the shape and structure of multicellular tissues in the process of morphogenesis. Our current understanding of morphogenesis has been limited by conceptual and technological barriers to dissecting the mechanical and molecular inputs that together coordinate cell behaviors. During this award, we will address these challenges and focus on resolving several key gaps in our understanding by: (1) elucidating how contractile and adhesive protein machineries in cells help coordinate activities between neighboring cells to give rise to collective cell and tissue movements and (2) dissecting how mechanical inputs integrate with molecular inputs to coordinate cell behaviors within tissues. Using the model organism Drosophila melanogaster, we are taking innovative approaches to address these questions in the context of epithelial tissue morphogenesis. To enable us to dissect mechanisms that coordinate cell behaviors, we are developing and using new technologies for controlling and quantifying the cell machineries and forces that drive these cell behaviors. These techniques, in combination with quantitative modeling, will allow us to dissect the molecular and mechanical mechanisms that coordinate cell behaviors within multicellular tissues. This work will provide a foundation for integrating mechanics into our understanding of how genetic and biochemical factors control development and may motivate new strategies for controlling tissue shape and structure in vivo and in vitro. More broadly, the tools and framework we develop will enable us to investigate the mechanisms that coordinate cell behaviors in a broad range of multicellular processes. A better understanding of the mechanisms underlying collective cell behaviors can elucidate general principles of self-organization in biological systems, provide insight into how improper regulation of these processes leads to human disease, and develop new approaches to manipulate these processes for therapeutic benefit.

项目摘要/摘要 胚胎发育过程中功能组织结构的形成取决于能力 细胞编排集体组织级运动。我的研究计划的目标是 了解细胞如何共同工作以共同生成多细胞的形状和结构 在形态发生过程中的组织。我们目前对形态发生的理解受到限制 通过概念和技术障碍来剖析机械和分子输入 共同协调细胞行为。在此奖项期间，我们将解决这些挑战，并关注 通过以下方式解决我们的理解中的几个关键差距：（1）阐明收缩和粘合蛋白的方式 细胞中的机器有助于协调相邻细胞之间的活动，从而产生集体电池 和组织运动，以及（2）解剖机械输入与分子输入的整合 协调组织内的细胞行为。使用模型有机体果蝇melanogaster，我们是 采用创新的方法在上皮组织的背景下解决这些问题 形态发生。为了使我们能够剖析协调细胞行为的机制，我们正在发展 并使用新技术来控制和量化驱动器的电池机器和力 这些细胞行为。这些技术与定量建模相结合，将使我们能够 解剖分子和机械机制，这些机制是在多细胞内协调细胞行为的 组织。这项工作将为将机械师整合到我们如何理解中的基础 遗传和生化因素控制开发，并可能激发控制的新策略 组织形状和结构在体内和体外。更广泛地，我们开发的工具和框架将会 使我们能够研究在多种细胞中协调细胞行为的机制 过程。更好地理解集体细胞行为的机制可以阐明 生物系统中自组织的一般原则，提供了有关如何不当的见解 这些过程的调节导致人类疾病，并开发了操纵的新方法 这些为治疗益处的过程。