Developing a lung organoid signalome for real-time analysis of senescence-associated cellular cross talk

开发肺类器官信号组用于实时分析衰老相关的细胞串扰

• 批准号: NC/X002063/1
• 负责人: Alison Elizabeth John
• 金额: $ 25.44万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FX002063%2F1
• 关键词: Developing; lung; organoid; signalome; real

Cells in our body suffer damage on a daily basis, and this is particularly true in the lungs which are constantly exposed to dangerous agents in the air that we breathe. In isolation, the effect of pollution, diesel particles, tobacco smoke, allergens and viral insults may be mild, but repeated exposure over many years can lead to development of diseases which have long term effects on lung health including Idiopathic Pulmonary Fibrosis (IPF) and Chronic Obstructive Pulmonary Disease (COPD). After exposure to an insult, the cells in the lung have to decide how to respond. In younger healthy individuals, lung cells will quickly repair themselves in response to a mild insult, restoring ormal lung function. As we age, the effect of years of repeated mild injuries leads the lung cells to respond in a different way, a process called cellular senescence. Senescent cells so not divide, so they are unable to aid in the repair of the lung following even mild injury. They also do not die. Instead they remain in the lungs and release signals which encourage neighbouring cells to also become senescent. Accumulation of these senescent, defective cells appears to contribute to the development of chronic lung disease although the exact process is unclear. We will create a 3D model of the human lung which contains two of the most important lung cell types, epithelial cells and fibroblasts. These cells will be modified so that they can change colour in response to signals generated by senescent cells. We will use this model to try and understand how healthy cells in the lung respond to signals from senescent cells, and how neighbouring cells influence each other's behaviour. Understanding how senescent cells increase in number in the aging lung could help us to identify new treatment to prevent these dysfunctional cells from collecting in the lung and causing disease.

我们身体中的细胞每天都会受到损害，尤其是肺部，它经常暴露在我们呼吸的空气中的危险物质中。孤立地说，污染、柴油颗粒、烟草烟雾、过敏原和病毒损伤的影响可能是轻微的，但多年重复暴露可导致对肺部健康具有长期影响的疾病的发展，包括特发性肺纤维化（IPF）和慢性阻塞性肺病（COPD）。在暴露于损伤后，肺中的细胞必须决定如何反应。在年轻的健康个体中，肺细胞会迅速修复自己，以应对轻微的损伤，恢复正常的肺功能。随着年龄的增长，多年重复轻微损伤的影响导致肺细胞以不同的方式做出反应，这一过程称为细胞衰老。衰老的细胞不会分裂，因此即使在轻微损伤后，它们也无法帮助修复肺部。他们也不会死。相反，它们留在肺部并释放信号，鼓励邻近细胞也变得衰老。这些衰老的缺陷细胞的积累似乎有助于慢性肺部疾病的发展，尽管确切的过程尚不清楚。我们将创建一个人肺的3D模型，其中包含两种最重要的肺细胞类型，上皮细胞和成纤维细胞。这些细胞将被修改，以便它们可以响应衰老细胞产生的信号而改变颜色。我们将使用这个模型来尝试和理解肺中的健康细胞如何响应衰老细胞的信号，以及相邻细胞如何影响彼此的行为。了解衰老细胞如何在衰老的肺中增加数量可以帮助我们找到新的治疗方法，以防止这些功能失调的细胞聚集在肺中并引起疾病。