Early-stage embryo as an active self-tuning soft material

作为主动自调节软材料的早期胚胎

• 批准号: EP/W023946/1
• 负责人: Kees Weijer
• 金额: $ 112.13万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FW023946%2F1
• 关键词: Early; stage; embryo; active; self

Embryonic development is a fascinating biological process in which a new organism is formed from a single cell, the fertilised egg or zygote. The process involves many rounds of cell growth and divisions to generate more cells, differentiation to generate different types of cells, and movements in order to arrange them in the complex structures of a functioning living organism. While in mammals the embryo receives necessary nutrients by being connected to the bloodstream of the mother, in the case of birds the nutrients come from the egg. Once the development of an egg is started, it is fully autonomous, the DNA of the zygote and the content of the egg contain the blueprint for building the entire organism. This requires a carefully timed and executed set of steps that involve complex biochemical and physical interactions between a rapidly growing number of differentiating cells.Gastrulation is an essential step in early development during which a single-layered sheet of cells, the blastula, transforms into a three-layered structure known as the gastrula. It sets up the layout of the body plan and when not executed properly results in abortion of development and, in milder cases, leads to a wide range of congenital defects. Gastrulation is highly evolutionally conserved between different vertebrate animal species, ranging from fish and frogs, via lizards and birds to mammals, including humans. Studying gastrulation, therefore, plays an important role in understanding the evolution of complex life. Gastrulation in birds shares a lot of similarities with the early development of human embryos. However, the fact that their embryos develop outside the mother animal, can be easily cultured, and are accessible to experimental observation and manipulation, make bird embryos an excellent model system for understanding the principles of early human development. The goal of this project is to identify, characterise, and understand essential biochemical and physical processes that drive gastrulation. Recent advances in live imaging showed that successful gastrulation depends on intimate coordination of gene expression, biochemical signalling, and mechanical stresses spanning from subcellular to cell to tissue scales. Therefore, understanding gastrulation is a complex task that requires shared expertise and close collaboration of a team of researchers with backgrounds in cell and developmental biology and physics. Here, we assemble such a team of experts. The team will use a combination of in-vivo and in-vitro imaging, mechanical, chemical, and genetic manipulations in conjunction with state-of-the-art modelling to understand how cell-level processes coordinate to drive complex motion patterns within the early chick embryo that allow cells to position themselves at the correct place in the embryo. Results of this study will have a long-lasting impact not only in developmental biology but on the general understanding of how biochemical and physical cues coordinate in living systems. Understanding the principles behind embryonic development would, therefore, be relevant to our understanding of the origin and evolution of life on Earth. It would also impact different branches of medical and biomedical research, ranging from understanding, preventing, and even treating congenital diseases, to treating severe injuries, to designing and building artificial tissues and organs. Beyond biomedical applications, being able to mimic embryonic development would revolutionise materials science by providing bottom-up fabrication processes -- instead of specifying the precise location of each component in complex circuitry in a top-down fashion, as it is the case today, one would "program" the building blocks with a set of rules and properties and let them self-assemble into a complex machine.

胚胎发育是一个令人着迷的生物过程，在这个过程中，一个新的有机体是由一个单一的细胞，受精卵或受精卵形成的。这个过程包括许多轮的细胞生长和分裂以产生更多的细胞，分化以产生不同类型的细胞，以及运动以将它们安排在功能正常的有机体的复杂结构中。在哺乳动物中，胚胎通过与母亲的血液相连来获得必要的营养，而在鸟类中，营养来自鸡蛋。一旦卵子开始发育，它就是完全自主的，受精卵的DNA和卵子的内容包含了构建整个有机体的蓝图。这需要一系列精心安排时间和执行的步骤，涉及数量迅速增加的分化细胞之间复杂的生化和物理相互作用。断奶是早期发育的关键步骤，在此过程中，单层细胞膜--囊胚--转变为称为原肠胚的三层结构。它设定了身体计划的布局，如果执行不当，会导致发育流产，在较轻的情况下，会导致广泛的先天性缺陷。原肠形成在不同的脊椎动物物种之间进化上高度保守，从鱼和青蛙，到蜥蜴和鸟类，再到哺乳动物，包括人类。因此，原肠胚的研究对于理解复杂生命的进化具有重要意义。鸟类的原肠发育与人类胚胎的早期发育有许多相似之处。然而，它们的胚胎在母动物之外发育，可以很容易地培养，并且可以进行实验观察和操作，这使得鸟类胚胎成为了解人类早期发育原理的一个很好的模型系统。这个项目的目标是识别、描述和了解驱动原肠形成的基本生化和物理过程。活体成像的最新进展表明，原肠胚的成功依赖于基因表达、生化信号和从亚细胞到细胞到组织尺度的机械应力的密切协调。因此，了解原肠形成是一项复杂的任务，需要具有细胞、发育生物学和物理学背景的研究人员共享专业知识和密切合作。在这里，我们聚集了这样一个专家团队。该团队将结合体内和体外成像、机械、化学和遗传操作，结合最先进的建模，了解细胞水平的过程如何协调，以驱动早期鸡胚中的复杂运动模式，使细胞能够将自己定位在胚胎中的正确位置。这项研究的结果不仅将对发育生物学产生持久的影响，而且将对生物化学和物理线索如何在生命系统中协调的一般理解产生持久的影响。因此，理解胚胎发育背后的原理将与我们理解地球上生命的起源和进化有关。它还将影响医学和生物医学研究的不同分支，从理解、预防甚至治疗先天性疾病，到治疗严重损伤，再到设计和建造人造组织和器官。除了生物医学应用，能够模拟胚胎发育将通过提供自下而上的制造过程来彻底改变材料科学--而不是像今天这样，以自上而下的方式在复杂的电路中指定每个组件的准确位置，人们将用一套规则和特性对构建块进行编程，并让它们自我组装成一台复杂的机器。

项目成果

The evolution of gastrulation morphologies.

胃形态的演变。

• DOI: 10.1242/dev.200885
• 发表时间: 2023-04-01
• 期刊: Development (Cambridge, England)

Linear viscoelastic response of the vertex model with internal and external dissipation: Normal modes analysis

• DOI: 10.1103/physrevresearch.5.013143
• 发表时间: 2022-02
• 期刊: Physical Review Research
• 影响因子: 4.2
• 作者: Sijie Tong;R. Sknepnek;A. Košmrlj