NSF-ANR: Collaborative Research: A mechanical atlas for embryogenesis at single-cell resolution
NSF-ANR:合作研究:单细胞分辨率胚胎发生机械图谱
基本信息
- 批准号:2204237
- 负责人:
- 金额:$ 38.54万
- 依托单位:
- 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:2022-05-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
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.
该项目的科学目标是加深对生命物质如何产生和控制机械力以塑造组织,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机械图谱的构建,描述了在三维空间中,以单细胞分辨率和随着时间的推移,在活胚胎中雕刻自己时的机械应力测量。然后,研究人员将在此基础上确定所观察到的压力模式的分子基础,并发现这些压力源共同确保独特形态发生结果的规则,这些规则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,对组织工程和器官再生领域产生直接影响。将开发的方法和工具将通过github作为开源共享;分割的胚胎和机械图谱将通过morphonet浏览器提供给社区。研究人员团队建议在海鞘胚胎的原肠胚形成过程中以3D和物理单位构建单细胞机械图谱。为此,他们将解决一个逆问题,该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。他们将使用这个机械图谱作为基础,探索肌动球蛋白如何动态控制力的产生,以及相邻细胞之间的动态耦合,编码鲁棒的定型形态发生轨迹。 特别是,研究人员将寻求确定1)有助于产生机械力模式的细胞之间的通信渠道,2)应力的分子发生器,3)机械力在改变细胞通信方式中的作用,以及4)观察到的机械应力模式如何塑造生物体的宏观形状。这项多方面的研究是通过4位科学家之间的高度跨学科合作而实现的,他们在发育生物学,物理学,应用数学和计算机科学方面具有独特和协同的专业知识。这项美国/法国合作项目得到了美国国家科学基金会和法国国家研究机构的支持,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。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Madhav Mani其他文献
Evolution of Generalists by Phenotypic Plasticity
表型可塑性的通才进化
- DOI:
10.1101/761288 - 发表时间:
2019 - 期刊:
- 影响因子:5.8
- 作者:
David T. Fraebel;K. Gowda;Madhav Mani;S. Kuehn - 通讯作者:
S. Kuehn
Active Tension Network model of epithelial mechanics
上皮力学的主动张力网络模型
- DOI:
- 发表时间:
2015 - 期刊:
- 影响因子:0
- 作者:
Nicholas Noll;Madhav Mani;Idse Heemskerk;S. Streichan;B. Shraiman - 通讯作者:
B. Shraiman
QuBiT: A quantitative tool for epithelial tubes reveals cell dynamics and unexpected patterns of organization during Drosophila tracheal morphogenesis
QuBiT:上皮管的定量工具揭示果蝇气管形态发生过程中的细胞动力学和意想不到的组织模式
- DOI:
10.1101/441600 - 发表时间:
2018 - 期刊:
- 影响因子:0
- 作者:
Ran Yang;Eric Li;Madhav Mani;G. Beitel - 通讯作者:
G. Beitel
The role of intracellular interactions in the collective polarization of tissues and its interplay with cellular geometry
细胞内相互作用在组织集体极化中的作用及其与细胞几何形状的相互作用
- DOI:
- 发表时间:
2018 - 期刊:
- 影响因子:0
- 作者:
S. Shadkhoo;Madhav Mani - 通讯作者:
Madhav Mani
A jump distance based parameter inference scheme for particulate trajectories in biological settings
基于跳跃距离的生物环境中颗粒轨迹参数推断方案
- DOI:
- 发表时间:
2017 - 期刊:
- 影响因子:0
- 作者:
Rebecca Menssen;Madhav Mani - 通讯作者:
Madhav Mani
Madhav Mani的其他文献
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{{ truncateString('Madhav Mani', 18)}}的其他基金
Collaborative Research: MTM 1: Decoding the genomic rules of denitrification in bacterial communities
合作研究:MTM 1:解码细菌群落反硝化的基因组规则
- 批准号:
2025521 - 财政年份:2020
- 资助金额:
$ 38.54万 - 项目类别:
Standard Grant
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- 项目类别:青年科学基金项目
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