Physics of Living Matter: From Molecule to Embryo

生命物质物理学：从分子到胚胎

• 批准号: 10676186
• 负责人: Sebastian J Streichan
• 金额: $ 35.61万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10676186
• 关键词: Advocate; Biological Models; Biophysics; Books; Cell Communication; Cell Shape; Cells; Congenital Abnormality; Cytoskeletal Modeling; Cytoskeletal Proteins; Cytoskeleton; DNA; Defect; Development; Developmental Biology; Embryo; Emerging Technologies; Fluorescence Microscopy; Foundations; Gene Expression Regulation; Genetic; Genetic Models; Genotype; Growth; Heart; Human; Image; Investigation; Language; Learning; Life; Light; Mechanical Stress; Mechanics; Microscopic; Microscopy; Modernization; Molecular; Molecular Biology; Morphogenesis; Organ; Organism; Pattern; Physics; Process; Resolution; Rest; Seminal; Shapes; Technology; Time; Tissues; Trees; Visit; cell behavior; congenital heart disorder; data handling; genetic information; imaging informatics; interdisciplinary approach; morphogens; predictive modeling; tool; transcription factor

ABSTRACT Organ form is vital for organisms to function properly. This is particularly evident for essential organs such as the human heart where shape defects result in congenital heart disease, a common birth defect. Despite major efforts, we still lack answers to this simple question: how does DNA encode shape? Developmental and molecular biology uncovered the principles of how maternal morphogens setup axes and trigger cascades of gene regulation to precisely determine cell fate patterns. Yet how the interplay of genetic information and mechanical activity orchestrates interaction of cells that shape organs remains elusive. In his seminal book “On growth and form” the polymath D'Arcy Thompson advocated for quantitative analysis of morphogenesis. His ideas where ahead of their time: they predate the genetic revolution, and many tools for quantitative analysis where missing. This proposal seeks to lay the foundations for quantitative morphogenesis, revisiting Thompson's agenda armed with the toolkit of the modern era. For a predictive understanding of morphogenesis, molecular investigation must be extended by quantitative analysis of tissue dynamics at the organ scale. At the organ scale concepts from physics of collective phenomena become relevant to study how thousands of cells streamline their `activity' to generate shape. Connecting developmental biology with physics harbors the promise to uncover new mechanisms at the organ scale. We know the transcription factors that determine fate, and cytoskeletal proteins that execute cell behaviors. Many of these players are conserved across a large portion of the tree of life. On the other hand, we learned shape of materials is determined by physical quantities such as force and mechanical stress. To unfold the full potential of an interdisciplinary approach, we need new tools bridging the gap between genetic players and physical quantitates. This approach will lead the way to the principles of morphogenesis. My team develops break through technology overcoming hurdles of whole organ quantitative analysis. Multi- view light sheet microscopy enables rapid in toto live imaging at subcellular resolution. Tissue cartography dives into the rest-frame of curved tissues and generates a panoramic overview, simplifying data handling and quantitative analysis. We pioneer biophysics-image-informatics to extract quantitative observables from fluorescence microscopy in the language of physics. Leveraging advanced understanding of the early embryo in the advanced genetic model system D. melanogaster, we aim for a comprehensive framework predicting how genotype determines tissue flows during axis elongation. Our approach will have a broad impact: by connecting development with physics we form the foundation of quantitative morphogenesis.

抽象的 器官形式对于有机体正常运行至关重要。这是基本器官（例如 形状缺陷的人心导致先天性心脏病，这是一种常见的先天缺陷。尽管很重要 努力，我们仍然缺乏这个简单问题的答案：DNA编码如何形状？发展和 分子生物学揭示了母体形态剂如何触发轴的原理 基因调节以精确确定细胞脂肪模式。然而，通用信息的相互作用如何 机械活动策划了形成器官的细胞相互作用，仍然难以捉摸。 在他的第二本书“关于成长和形式”的书中，主张进行定量分析的Polymath d'Arcy Thompson 形态发生。他的想法在他们的时间之前：他们早于遗传革命，还有许多工具 缺失的定量分析。该建议旨在为定量奠定基础 形态发生，重新审视汤普森的议程，由现代时代的工具包。用于预测 了解形态发生，必须通过定量分析扩展分子研究 在器官尺度上的组织动力学。从集体现象物理学的器官量表概念 研究成千上万个细胞如何简化其“活性”以产生形状的意义很重要。连接 物理学的发育生物学藏有希望在器官尺度上发现新机制的承诺。我们 了解确定命运的转录因子以及执行细胞行为的细胞骨架蛋白。许多 这些参与者中有一大批生命树是保守的。另一方面，我们学会了形状 材料由诸如力和机械应力之类的物理量确定。展开全部 跨学科方法的潜力，我们需要新工具，弥合遗传参与者与 物理定量。这种方法将导致形态发生的原理。 我的团队正在开发突破技术克服整个器官定量分析的障碍。多- 查看轻度显微镜可以在亚细胞分辨率下快速进行实时成像。组织制图 潜入弯曲组织的其余框架中，并生成全景概述，简化数据处理和 定量分析。我们开创了生物物理学图像信息，以从中提取定量可观察物 物理语言中的荧光显微镜。利用对早期胚胎的高级理解 在先进的遗传模型系统D. Melanogaster中，我们的目标是一个全面的框架来预测 基因型如何决定轴伸长过程中的组织流。我们的方法将产生广泛的影响： 将发育与物理联系起来，我们构成了定量形态发生的基础。

项目成果

Geometric control of myosin II orientation during axis elongation.

• DOI: 10.7554/elife.78787
• 发表时间: 2023-01-30
• 期刊: eLife
• 影响因子: 7.7
• 作者: Lefebvre MF;Claussen NH;Mitchell NP;Gustafson HJ;Streichan SJ
• 通讯作者: Streichan SJ

A Geometric Tension Dynamics Model of Epithelial Convergent Extension.

上皮收敛延伸的几何张力动力学模型。

• 发表时间: 2023
• 期刊: ArXiv
• 作者: Claussen,NikolasH;Brauns,Fridtjof;Shraiman,BorisI
• 通讯作者: Shraiman,BorisI

Patterned mechanical feedback establishes a global myosin gradient.

• DOI: 10.1038/s41467-022-34518-9
• 发表时间: 2022-11-17
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Gustafson, Hannah J.;Claussen, Nikolas;De Renzis, Stefano;Streichan, Sebastian J.
• 通讯作者: Streichan, Sebastian J.

Active cell divisions generate fourfold orientationally ordered phase in living tissue.

• DOI: 10.1038/s41567-023-02025-3
• 发表时间: 2023-08
• 期刊: Nature physics
• 影响因子: 19.6

The Geometric Basis of Epithelial Convergent Extension.

上皮会聚延伸的几何基础。

• DOI: 10.1101/2023.05.30.542935
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Brauns,Fridtjof;Claussen,NikolasH;Wieschaus,EricF;Shraiman,BorisI
• 通讯作者: Shraiman,BorisI