Mis-programming of mesenchymal progenitor cells in human lung fibrosis.

纤维化是炎性疾病的常见终点，并且涉及全世界>20%的死亡。在2019冠状病毒病大流行期间，我们是全球首个在2019冠状病毒病感染后12个月发现长期COVID纤维化的团队，了解炎症进展为纤维化的原因的重要性进一步增加。在南安普顿大学的肺纤维化小组中，我们应用最先进的技术，整合了结构、分子和组织生物学方法，包括空间转录组学，以确定人类肺微环境中的关键因素，这些因素决定了为什么在某些个体中发生纤维化进展而不是正常的组织修复。我们使用人类肺纤维化微环境的先进3D模型来研究潜在机制，并与Pharma合作研究治疗靶向。该项目将研究间充质细胞的错误编程在进行性纤维化中起关键作用的假设，重点关注我们最近发现的关键途径。所使用的技术组合将取决于学生的偏好和最适合的方法，以实现项目开始前定义的详细目标。该项目将提供最先进的方法，包括先进的3D细胞培养，分子生物学，蛋白质组学和大型数据集（包括空间转录组学）的计算分析。您将使用基因编辑和小分子抑制剂方法进行机制研究，研究纤维化组织工程模型中的功能后果。

Fibrosis is a common endpoint of inflammatory diseases and is implicated in >20% of deaths in worldwide. The importance of understanding why inflammation progresses to fibrosis has further increased during the COVID-19 pandemic where we were the first group worldwide to identify the presence of long COVID fibrosis at 12 months after COVID-19 infection. In the Lung Fibrosis Group at the University of Southampton we apply state-of-the-art technologies integrating structural, molecular, and tissue biology approaches including spatial transcriptomics to identify the key factors in the human lung microenvironment that determine why in some individuals fibrosis progresses rather than normal tissue repair occurs. We translate our findings using advanced 3D models of the human lung fibrosis microenvironment to investigate underlying mechanisms, and work in collaboration with Pharma to investigate therapeutic targeting.This project will investigate the hypothesis that misprogramming of mesenchymal cells plays a key role in progressive fibrosis, focusing on key pathways that we have recently identfied. The mix of techniques used will depend on student preference and the most suitable approaches to the detailed aims defined prior to the start of the project. The project will provide excellent wide-ranging training in state-of-the-art methodologies including advanced 3D cell culture, molecular biology, proteomics, and computational analysis of large datasets including spatial transcriptomics. You will perform mechanistic studies using gene editing and small molecule inhibitor approaches, investigating functional consequences within tissue-engineered models of fibrosis.