Investigating the molecular basis of basement membrane specialisation and basal surface organisation during epithelial tissue development

研究上皮组织发育过程中基底膜特化和基底表面组织的分子基础

• 批准号: MR/Y012089/1
• 负责人: Franck Pichaud
• 金额: $ 69.32万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY012089%2F1
• 关键词: Investigating; molecular; basis; basement; membrane

Cells are the building blocks that make up our organs. Our goal is to understand how during development, epithelial cells, which are found in most of our organs, coordinate changes in their shape to generate complex three dimensional structures, including tubes, folds and cavities, vital for organ function. One of the reasons we are interested in epithelial cell and tissue shape control is because abnormal epithelial tissue organisation has been implicated in many diseases, including in colon, stomach, breast, and lung cancer, for example. To uncover how changes in cell shape can be coordinated across a tissue to generate a healthy, functioning epithelial structure, we will use the Drosophila (fruit fly) retina, where we can use a broad range of genetic tools to manipulate the function of candidate molecular machinery involved in cell shape control, while studying the effect these manipulations have on cells and tissue shape in a living animal, as the organ develops. With this powerful approach, we have recently discovered that cells can communicate with each other to coordinate changes in their shape through a molecule called Laminin, a gel-like substance that lines the bottom surface of cells in flies and human alike. Our objective is to further investigate this communication process in a simple animal system and understand how it helps coordinate the changes in cells that shape the tissues in our organs. This knowledge will help us comprehend how epithelial tissues develop in general and we hope, will contribute to better understanding the causes of diseases linked to abnormal epithelial tissue organisation and mutation in Laminins, which have been implicated in a range of pathologies in humans.

细胞是构成我们器官的基础。我们的目标是了解在开发过程中，在我们大多数器官中发现的上皮细胞如何协调其形状的变化，以产生复杂的三维结构，包括管，褶皱和空腔，对器官功能至关重要。我们对上皮细胞和组织形状控制感兴趣的原因之一是因为异常上皮组织组织与许多疾病有关，包括在结肠，胃，乳腺癌和肺癌中。为了发现如何在组织中配位细胞形状的变化以产生健康，功能正常的上皮结构，我们将使用果蝇（果蝇）视网膜，我们可以使用广泛的遗传工具来操纵候选分子机械的功能，同时研究这些手动对细胞和组织的影响，从而使动物形成生命。通过这种强大的方法，我们最近发现，细胞可以通过称为层粘连蛋白的分子（一种凝胶状物质，在苍蝇和人类中都在细胞的底部表面排列的凝胶状物质，以互相交流以协调其形状的变化。我们的目标是在简单的动物系统中进一步研究这一通信过程，并了解它如何帮助协调塑造器官中组织的细胞变化。这些知识将有助于我们理解上皮组织如何发展，我们希望，将有助于更好地理解与异常上皮组织组织和层粘连蛋白突变有关的疾病的原因，这些疾病与人类的一系列病理相关。