Graph-based network models of cell-signalling in Idiopathic Pulmonary Fibrosis: integrated in silico and wet-lab approaches

特发性肺纤维化细胞信号传导的基于图的网络模型：集成到计算机和湿实验室方法中

• 批准号: 2136842
• 金额: --
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2136842
• 关键词: Graph; based; network; models; cell

The project looks to investigate the key cell signalling pathways associated with Idiopathic Pulmonary Fibrosis (IPF). IPF is an incurable lung disease with a poor prognosis of 2-4 years survival from time of diagnosis. Currently there is not a full understanding of the key driving mechanisms associated with the disease, which is a problem to be addressed in this research. The Wnt signalling pathway has been identified as one that plays an essential role in the communication between epithelial and fibroblast cells. However, although Wnt is well understood at an intracellular level, how the pathway is able to drive the development of lung fibroses is unclear. Throughout the project, large datasets will be used to extract mechanistic information relating to IPF, which can then be tested using wet-lab techniques. Using this combination of in silico and in vitro methods, it is hoped to identify key signalling pathways that drive IPF progression, in particular looking at the differences between canonical and non-canonical Wnt signalling. Upon identification of key mechanisms, it is planned to highlight novel drug targets and potentially look to develop ligands or proteins that can act on these sites, in order to halt IPF development.

该项目旨在研究与特发性肺纤维化（IPF）相关的关键细胞信号通路。 IPF 是一种无法治愈的肺部疾病，预后不良，自诊断之日起生存期为 2-4 年。目前对该疾病相关的关键驱动机制尚未完全了解，这是本研究需要解决的问题。 Wnt 信号通路已被确定为在上皮细胞和成纤维细胞之间的通讯中发挥重要作用的信号通路。然而，尽管 Wnt 在细胞内水平上已得到充分了解，但该途径如何驱动肺纤维化的发展尚不清楚。在整个项目中，大型数据集将用于提取与 IPF 相关的机械信息，然后可以使用湿实验室技术进行测试。通过结合计算机和体外方法，希望能够确定驱动 IPF 进展的关键信号通路，特别是观察经典和非经典 Wnt 信号传导之间的差异。在确定关键机制后，计划突出新的药物靶点，并可能寻求开发可以作用于这些位点的配体或蛋白质，以阻止 IPF 的发展。