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

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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.