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

生物学的一个核心挑战是了解细胞群如何在早期发育过程中快速集体变形。 基于肌动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-细胞接触传递这些力。 这些网络必须随着细胞的移动、分裂和交换邻居而不断地重塑自己。但它们是如何做到这一点的，以及它们如何塑造另一个的组织和动态，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和数学建模。 除了对控制早期胚胎快速重塑的机制提供新的见解之外。该项目将为学生提供在生物学，物理学和数学的边界有价值的交叉训练。 PI将把这项工作中出现的概念和方法纳入本科生和研究生阶段的生物动力学课程，并进入一个新的显微镜实践课程将在MBL教授。这个多学科的合作努力的目标是了解力传递的宏观动力学如何从早期C的微观动力学和收缩和粘附网络的耦合中出现。线虫胚胎我们将利用尖端的显微镜工具来表征粘附网络组装和重塑的微观动力学，因为新的接触形式和增长。我们将确定肌动蛋白网络结构、收缩力和流动如何塑造粘附网络的结构，以及收缩力和流动的模式如何反过来通过细胞-细胞接触处的收缩网络的锚定来塑造。最后，我们将使用物理理论和建模，受微观观察和生物物理测量的约束，以了解这两个网络之间的物理耦合如何控制摩擦滑动和接触力传递的平衡。这项工作将产生基本的新见解，即早期胚胎如何使用高度保守的控制收缩性和粘附性的分子机制来协调快速重塑。 它将为研究生和本科生提供一个独特的跨学科培训机会，这项工作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。其中NSF资助美国调查员，ANR资助法国的合作伙伴。该奖项反映了NSF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。

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.