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获得和组织形状的生物学和物理学原理。发育器官通常从简单的组织开始，通常是扁平的，只包含几种细胞类型。然后，组织“自我组织”，这意味着它产生新的形状和细胞命运，而无需进一步的外部输入。了解从最初的平面生成复杂的3D形状的组织仍然是生物学中的一个主要挑战。这个过程是由细胞的分子和机械特性的变化驱动的，这些细胞塑造了组织的形式和功能。这个过程是迭代的;例如，当不同谱系的细胞之间形成新的接触时，组织的进一步循环就会发生。因此，理解形态发生是物理学和生物学之间的接口，因为它涉及到力学和基因表达的变化周期，这些变化在多个时空尺度上反馈。类器官最近成为研究人类器官发育的有力工具。尽管在一系列类器官方面取得了重大进展，特别是在复制体内细胞命运决策方面，但塑造器官的生物物理过程仍然缺乏特征。在这个项目中，Ryan将利用神经元;这个系统复制了早期人类神经系统的发育。赖安会在沃里克培养类神经细胞。他将使用最先进的荧光成像工具：配备深层组织成像物镜的旋转圆盘显微镜;和双光子显微镜。此外，Ryan将建立一个图像分析管道来提取神经元样形态发生过程中的3D细胞形状，细胞跟踪和命运。细胞在形态发生过程中如何迁移，以及细胞命运如何反馈到细胞运动中;2.对培养物大小的限制如何影响细胞动力学和由此产生的器官形状;3.潜在几何形状的不对称性（例如圆形或三角形区域上的细胞）是否会改变器官形态发生，如果是，如何改变？该项目汇集了类器官和成像的最新技术，以解决与MRC相关的一个主要问题：复杂的器官形状是如何出现的？这些信息对于理解成人因发育过程中的缺陷而导致的疾病具有高度相关性。