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

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是一种不能治愈的肺部疾病，从确诊之日起2-4年存活期预后较差。目前对与该病相关的关键驱动机制还没有完全的了解，这是本研究需要解决的一个问题。Wnt信号通路在上皮细胞和成纤维细胞之间的通讯中起着至关重要的作用。然而，尽管Wnt在细胞内水平上被很好地理解，但该途径如何能够驱动肺纤维化的发展尚不清楚。在整个项目中，将使用大型数据集来提取与IPF相关的机械信息，然后可以使用湿实验室技术进行测试。利用这种在计算机和体外方法的结合，人们希望识别驱动IPF进展的关键信号通路，特别是观察规范和非规范Wnt信号之间的差异。在确定关键机制后，计划突出新的药物靶点，并可能寻求开发能够作用于这些部位的配体或蛋白质，以阻止IPF的发展。

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.