NSF-ANR: Co-Dynamics of Contraction and Adhesion in Animal Morphogenesis

NSF-ANR：动物形态发生中收缩和粘附的协同动力学

• 批准号: 2204227
• 负责人: Edwin Munro
• 金额: $ 57.63万
• 依托单位: University of Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2204227&HistoricalAwards=false
• 关键词: NSF; ANR; Co; Dynamics; Contraction

A central challenge in biology is to understand how groups of cells rapidly and collectively deform themselves during early development. Actomyosin-based contractile networks produce the forces that deform cells, while adhesion networks transmit those forces across cell-cell contacts. These networks must continuously remodel themselves as cells move, divide and exchange neighbors. But how they do so, and how each shapes the organization and dynamics of the other, remains poorly understood. We will address this challenge in nematode worm embryos, combining advanced microscopy, genetic and biophysical manipulations and mathematical modeling. In addition to providing new insight into mechanisms that govern the rapid remodeling of early embryos. The project will provide students with valuable cross-training at boundaries of biology, physics and mathematics. The PI will incorporate concepts and methods emerging from this work into undergraduate and graduate level courses in biological dynamics, and into a new practical course in microscopy to be taught at the MBL.The goal of this multidisciplinary collaborative effort is to understand how the macroscopic dynamics of force transmission emerge from the microscopic dynamics and coupling of contractile and adhesion networks in early C. elegans embryos. We will leverage cutting edge microscopy tools to characterize the microscopic dynamics of adhesion network assembly and remodeling as new contacts form and grow. We will determine how the architecture of adhesion networks are shaped by actin network architecture, contractility and flow, and how in turn, patterns of contractility and flow are shaped by anchorage of contractile networks at cell-cell contacts. Finally, we will use physical theory and modeling, constrained by microscopic observations and biophysical measurements, to understand how physical coupling between these two networks controls the balance of frictional slippage and force transmission across contacts. This work will yield fundamental new insights into how early embryos can orchestrate rapid remodeling using the highly conserved molecular machinery that governs contractility and adhesion. It will provide a unique interdisciplinary training opportunity for both graduate and undergraduate students, and the conceptual and methodological results from this work will inform the development of new lectures and course modules for two quantitative biology courses and a new hands-on microscopy course taught by the PI.This collaborative US/France project is supported by the US National Science Foundation and the French Agence Nationale de la Recherche, where NSF funds the US investigator and ANR funds the partners in France.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

生物学的一个核心挑战是理解细胞群如何在早期发育过程中迅速集体变形。基于肌动球蛋白的收缩网络产生使细胞变形的力，而粘附网络通过细胞间的接触传递这些力。当细胞移动、分裂和交换邻居时，这些网络必须不断地自我改造。但它们是如何做到这一点的，以及每一种如何塑造另一种的组织和动态，人们仍然知之甚少。我们将在线虫胚胎中解决这一挑战，结合先进的显微镜，遗传和生物物理操作以及数学建模。除了提供对控制早期胚胎快速重塑机制的新见解之外。该项目将为学生提供宝贵的生物学、物理学和数学交叉训练。该项目将把从这项工作中产生的概念和方法纳入生物动力学的本科和研究生课程，以及MBL教授的一门新的显微镜实践课程。这项多学科合作的目标是了解早期秀丽隐杆线虫胚胎中力传递的宏观动力学是如何从微观动力学和收缩和粘附网络的耦合中产生的。我们将利用尖端的显微镜工具来表征新接触形成和生长时粘附网络组装和重塑的微观动力学。我们将确定粘连网络的结构是如何被肌动蛋白网络结构、收缩性和流动所塑造的，以及反过来，收缩性和流动的模式是如何被细胞-细胞接触处的收缩网络锚定所塑造的。最后，我们将利用物理理论和建模，在微观观察和生物物理测量的约束下，了解这两个网络之间的物理耦合如何控制摩擦滑移和接触面间力传递的平衡。这项工作将对早期胚胎如何利用控制收缩性和粘附性的高度保守的分子机制来协调快速重塑产生根本性的新见解。它将为研究生和本科生提供一个独特的跨学科培训机会，从这项工作中获得的概念和方法结果将为PI教授的两门定量生物学课程和一门新的动手显微镜课程的新讲座和课程模块的开发提供信息。这个美国/法国合作项目由美国国家科学基金会和法国国家研究机构支持，其中美国国家科学基金会资助美国研究者，法国国家研究机构资助法国合作伙伴。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。