NSF-ANR: Collaborative Research: A mechanical atlas for embryogenesis at single-cell resolution

这个项目的科学目标是加深对生物如何产生和控制机械力来塑造组织、器官和生物体的理解。激励和指导拟议工作的核心技术创新是建立一个机械地图集，描述在活胚胎塑造自己的过程中，以三维、单细胞分辨率和随时间的变化测量机械应力。然后，研究人员将在这一努力的基础上，确定观察到的应激模式的分子基础，并发现这些应激源共同确保独特的形态发生结果的规则，这些方式对于表型和环境变化是稳健的。他们预计，这项工作将揭示胚胎发育的新机械设计原则，直接影响组织工程和器官再生领域。将开发的方法和工具将通过GitHub作为开源共享；分段胚胎和机械图谱将通过Moronet浏览器提供给社区。研究小组建议在海鞘胚胎原肠形成过程中以3D和物理单位构建单细胞机械图谱。为此，他们将解决一个反问题，基于多细胞聚集体的新物理理论，先进的基于光片的成像，以及材料参数的生物物理测量。他们将利用这一机械图谱作为基础，探索肌动球蛋白对力产生的动态控制，以及相邻细胞之间的动态耦合，如何编码稳健的刻板印象的形态发生轨迹。特别是，研究人员将试图确定1)有助于产生机械力模式的细胞之间的通信渠道，2)应力的分子生成器(S)，3)机械力在改变细胞交流方式中所起的作用，以及4)观察到的机械应力模式如何塑造有机体的宏观形状。这项多方面的研究是通过4位在发育生物学、物理学、应用数学和计算机科学方面具有独特和协同专业知识的科学家之间的高度跨学科合作而成为可能的。这个美法合作项目得到了美国国家科学基金会和法国国家科学基金会的支持，其中NSF资助美国研究人员，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智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The scientific goal of this project is to deepen the understanding of how living matter generates and controls mechanical forces to shape tissues, organs, and organisms. The central technological innovation that motivates and guides the proposed work is the construction of a Mechanical Atlas, describing the measurement of mechanical stresses, in three dimensions, at single-cell resolution and over time, in a living embryo as it sculpts itself. The investigators will then build on this effort to determine the molecular underpinnings of the observed patterns of stress, and discover rules by which these stressors collectively ensure unique morphogenetic outcomes in ways that are robust with respect to phenotypic and environmental variations. They expect this work will reveal new mechanical design principles for embryonic development, with direct impact on the fields of tissue engineering and organ regeneration. The methodology and tools that will be developed will be shared as open source through github; segmented embryos and the mechanical atlas will be made available to the community through the morphonet browser.The team of investigators propose to construct a single-cell mechanical atlas, in 3D and in physical units, during the process of gastrulation in the ascidian embryo. To do so, they will solve an inverse problem, grounded in a new physical theory of multicellular aggregates, advanced light-sheet based imaging, and biophysical measurements of material parameters. They will use this mechanical atlas as a foundation to explore how dynamic control of force generation by actomyosin, and dynamic coupling between neighboring cells, encodes robust stereotyped morphogenetic trajectories. In particular, the investigators will seek to determine 1) communication channels between cells that contribute to the generating the patterns of mechanical forces, 2) the molecular generator(s) of stress, 3) the roles that mechanical forces play in altering how cells communicate, and 4) how the observed patterns of mechanical stress sculpt the macroscopic shape of the organism. This multifaceted research is made possible through a highly interdisciplinary collaboration between 4 scientists with distinct and synergistic expertise in developmental biology, physics, applied mathematics and computer science.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.