Determining the role of boundary constraints and initial conditions on 4D cell morphodynamics during neural development.

确定神经发育过程中边界约束和初始条件对 4D 细胞形态动力学的作用。

• 批准号: 2597043
• 金额: --
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2597043
• 关键词: Determining; role; boundary; constraints; initial

The aim of the project is to understand the biological and physical principles that underlie the acquisition and organisation of tissue shape.Developing organs typically start as simple tissues, which are often flat and contain only a few cell types. The tissue then "self-organises", meaning that it generates new shapes and cell fates without further external inputs. Understanding the generation of complex 3D shaped tissues from initially flat sheets remains a major challenge in biology. This process is driven by changes in the molecular and mechanical properties of the cells that shape the form and function of tissues. This process is iterative; e.g. as new contacts form between cells of different lineages, further rounds of organisation take place. Thus, understandingmorphogenesis lies at the interface between physics and biology as it involves cycles of changes in mechanics and gene expression that feedback across multiple spatiotemporal scales. Organoids have recently emerged as a powerful tool for investigating human organ development. Despite significant progress being made in a range of organoids, especially to replicate in vivo cell fate decision making, the biophysical processes that shape organs remain poorly characterised.In this project, Ryan will take advantage of neuruloids; this system replicates developmentof the early human nervous system. Ryan will culture neuruloids at Warwick. He will use state-of-the-art fluorescent imaging tools: spinning disc microscopy equipped with objectives for deep tissue imaging; and 2-photon microscopy. Further, Ryan will build an image analysis pipeline to extract 3D cell shape, cell tracking, and fate during neuruloid morphogenesis.Using this quantitative framework, we will address:1. how cells migrate during morphogenesis, and how cell fate feeds back into cellular motion;2. how constraints on culture size affect cell dynamics and the resulting organ shape;3. whether asymmetries in the underlying geometry (e.g. cells on either circular or triangular domains) alters organ morphogenesis, and if so, how?This project brings together the latest technologies in organoids and imaging to tackle a major question relevant to the MRC: how does complex organ shape emerge? Such information is highly pertinen to understanding diseases in adult which derive from defects during development.

该项目的目的是了解组织形状的获取和组织的生物学和物理原理。开发器官通常以简单的组织开始，这些组织通常是平坦的，仅包含几种细胞类型。然后组织“自组织”，这意味着它会产生新的形状和细胞命运，而无需进一步的外部输入。了解最初扁平床单的复杂3D形状组织的产生仍然是生物学的主要挑战。该过程是由形成组织形式和功能的细胞的分子和机械性能的变化所驱动的。这个过程是迭代的；例如随着不同谱系细胞之间的新触点形成，组织的进一步回合。因此，理解形态发生在于物理学与生物学之间的界面，因为它涉及机械变化和基因表达的循环，这些变化是跨多个时空尺度反馈的。器官最近已成为研究人体器官发育的强大工具。尽管在各种器官中取得了重大进展，尤其是在体内细胞命运决策中复制，但塑造器官的生物物理过程仍然很差。该系统复制了早期人类神经系统的发展。瑞安（Ryan）将在沃里克（Warwick）培养神经素。他将使用最先进的荧光成像工具：配备有深层组织成像目标的旋转盘显微镜；和2光子显微镜。此外，瑞安（Ryan）将建立一个图像分析管道，以提取神经素形态发生过程中的3D细胞形状，细胞跟踪和命运。使用此定量框架，我们将解决：1。细胞在形态发生过程中的迁移以及细胞命运如何反馈到细胞运动中； 2。培养大小的约束如何影响细胞动力学和所得的器官形状； 3。潜在几何形状（例如圆形或三角形结构域的细胞）中的不对称性是否会改变器官形态发生，如果是这样，该项目如何汇集器官和成像中的最新技术，以解决与MRC相关的主要问题：如何形成复杂的器官形状？这些信息非常详细，是理解成年人的疾病，这些疾病是从发育过程中的缺陷中获得的。