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.

细胞是组成我们器官的基本单位。我们的目标是了解在发育过程中，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的上皮组织结构与许多疾病有关，包括结肠癌、胃癌、乳腺癌和肺癌。为了揭示细胞形状的变化如何在整个组织中协调以产生健康，功能正常的上皮结构，我们将使用果蝇（果蝇）视网膜，在那里我们可以使用广泛的遗传工具来操纵参与细胞形状控制的候选分子机制的功能，同时研究这些操纵对活体动物中细胞和组织形状的影响，随着器官的发育。通过这种强大的方法，我们最近发现细胞可以通过一种名为层粘连蛋白的分子相互交流，以协调其形状的变化，层粘连蛋白是一种凝胶状物质，排列在苍蝇和人类细胞的底部表面。我们的目标是在一个简单的动物系统中进一步研究这种通信过程，并了解它如何帮助协调塑造我们器官组织的细胞变化。这些知识将帮助我们理解上皮组织一般是如何发育的，我们希望这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相关的疾病的原因，这些疾病与人类的一系列病理学有关。