The Role of Mechanical Interactions in Tissue Formation and Body Axis Specification

尽管它们有着惊人的多样性，但所有的动物都是从一个受精卵开始的。如何从一个最初接近一致的系统--鸡蛋--建立模式，是生物学中的一个基本问题。细胞与环境之间的机械相互作用被认为在组织和轴的形成中发挥着重要作用，但由于胚胎发育的复杂性，这一点很难通过实验进行剖析。该奖项将调查机械力在从分离细胞的溶液中形成九头蛇身体形态中的作用。细胞表面的张力和细胞分泌的组织纤维层的硬度如何改变动物结构的发育也将被测量。该奖项支持旨在研究一种简单动物的基础研究，这种动物在分离成单个细胞后可以再生自己的身体。体型发育过程中细胞-细胞相互作用的核心力学机制在早期发育过程中是普遍存在的。了解这些机制是如何在一个简单的有机体中工作的，将有助于深入了解更复杂的生物中的这些机制。这项研究可能揭示组织组装和器官形成的一般指导原则，从而对移植组织和器官工程背景下的医学具有指导意义。了解有机体是如何从细胞聚集体中出现的，这激发了人类的想象力。因此，该项目将为本科生和研究生提供令人兴奋的研究机会。该项目的跨学科性质需要应用物理学、生物学、工程学和计算机科学的工具，因此将使来自不同背景的学生做出重大贡献。剖析动物发育中涉及的机械相互作用在实验上是具有挑战性的。一个有望实现这种解剖的新系统是淡水息肉九头蛇，它会自我组织，并在分解成单细胞悬浮液后再生。由于这种非凡的能力和结构的简单性，再生的九头蛇聚集体完全可以进行定量测量和受控扰动，同时提供一个使测量有意义的体内环境。这项研究将阐明细胞悬液如何形成组织，并确定导致体轴规范的机制。对于这两个过程，研究小组将应用从分子到生物层面的多尺度方法，并使用物理测量、化学操作、使用转基因动物和免疫组织化学显示基因表达以及荧光延时显微镜来测试机械相互作用的重要性。这项研究将为宏观生物体水平的模式如何从细胞水平上的相互作用中出现提供洞察力。

Despite their remarkable diversity, all animals begin as a single, fertilized egg. How patterns are established from an initially near uniform system, the egg, is a fundamental question in biology. Mechanical interactions between cells and their environment are thought to play an important role in tissue and axis formation, but this has been difficult to dissect experimentally because of the complexity of developing embryos. The award will investigate the role of mechanical forces in the formation of body form of the Hydra from a solution of separated cells. How the tension at the cell surface and the stiffness of layers of tissue fibers that the cells secrete change how the animal structure develops also will be measured. This award supports fundamental research aimed at studying a simple animal that can regenerate its body after dissociation into individual cells. The core mechanical mechanisms of cell-cell interactions during body plan development are universal during early development. Understanding how these mechanisms work in a simple organism will lead to insight into these mechanisms in more complex beings. This research may reveal general guiding principles for tissue assembly and organ formation and thus has implications for medicine in the context of engineering tissues and organs for transplantation. Understanding how an organism can emerge from an aggregation of cells sparks human imagination. Therefore this project will offer exciting research opportunities for undergraduate and graduate students. The interdisciplinary nature of the project requires the application of tools from physics, biology, engineering, and computer science, and thus will enable students from diverse backgrounds to make significant contributions.It is experimentally challenging to dissect the mechanical interactions involved in animal development. A novel system which promises to allow such a dissection is the freshwater polyp Hydra, which self-organizes and regenerates after dissociation into a suspension of single cells. Because of this remarkable ability and its structural simplicity, regenerating Hydra aggregates are fully accessible to quantitative measurements and controlled perturbations while providing an in vivo environment that makes the measurements meaningful. This research will elucidate how tissue formation occurs from a cell suspension and determine the mechanisms that lead to body axis specification. For both processes, the research team will apply a multiscale approach from the molecular to the organismal level and test the importance of mechanical interactions using physical measurements, chemical manipulations, visualization of gene expression using transgenic animals and immunohistochemistry, and fluorescent time-lapse microscopy. This study will provide insight into how macroscopic organism-level patterning emerges from interactions on the cellular level.