Physics of Living Matter: From Molecule to Embryo

摘要 器官形态对生物体的正常运作至关重要。这一点对必要的器官尤其明显，如 人类心脏的形状缺陷会导致先天性心脏病，这是一种常见的出生缺陷。尽管有重大的 尽管我们努力了，但我们仍然没有答案这个简单的问题：DNA是如何编码形成的？发展和 分子生物学揭示了母体形态起源如何建立轴和触发级联反应的原理 精确决定细胞命运模式的基因调控。然而，遗传信息和遗传信息之间的相互作用 机械活动协调形成器官的细胞之间的相互作用仍然难以捉摸。 在他的开创性著作《论生长和形式》中，博学的达西·汤普森主张进行定量分析 形态发生的特征。他的想法走在了时代的前面：它们早于基因革命，以及许多用于 缺失的地方进行了定量分析。这项提议旨在为量化 形态发生，重温汤普森的议程，用现代的工具包武装起来。对于预测性的 理解形态发生，分子研究必须通过定量分析来扩展 器官尺度上的组织动力学。在器官尺度上，来自集体现象物理学的概念 变得与研究数千个细胞如何流线化它们的“活动”以产生形状有关。连接 发育生物学与物理学相结合，有望在器官层面上发现新的机制。我们 了解决定命运的转录因子，以及执行细胞行为的细胞骨架蛋白。许多 在生命之树的很大一部分中，这些玩家是被保存下来的。另一方面，我们学习了形状 材料的强度由力和机械应力等物理量决定。全面展开 跨学科方法的潜力，我们需要新的工具来弥合遗传参与者和 物理量。这种方法将引导我们走上形态发生原理的道路。 我的团队开发了突破整体器官定量分析障碍的技术。多个- 查看光片显微镜可以实现亚细胞分辨率的快速全景实时成像。组织制图学 深入到弯曲组织的静止框架并生成全景概览，简化了数据处理和 定量分析。我们开创了生物物理学-图像-信息学的先河，从 物理语言中的荧光显微镜。利用对早期胚胎的高级理解 在高级遗传模型系统D.Blackogaster中，我们的目标是建立一个全面的框架预测 在轴伸长过程中，基因如何决定组织流动。我们的方法将产生广泛的影响：通过 我们把发展与物理联系起来，形成了定量形态发生的基础。

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.