Discovering Collagen I degradation process in chronic diseases with fibrotic component

ongoing

Fibrosis-related chronic diseases (CDs) are amongst the biggest societal burdens in Europe, with fibrosis being recognised as the main driver of morbidity and mortality. Extracellular matrix (ECM) is a key player in fibrosis, with an excessive accumulation of type I collagen (COL1) being a predominant component of the fibrotic tissue. While the increase in COL1 production is considered a main driver of fibrosis, respective drugs had limited efficacy. New evidence indicates that attenuation of COL1 degradation is highly relevant, contributing to onset and progression of fibrosis. Ambitious early stage researchers (ESRs) will join forces within a multi-disciplinary, comprehensive and inter-sectoral doctorate training programme, embedded in an existing network of excellent research groups across Europe, to investigate the “outside-the-box idea” on impaired COL1 degradation being a key driver of fibrosis. The main scientific goal is to improve the understanding of molecular mechanisms associated with COL1 degradation in major fibrosis-related CDs, and investigate the disruptive hypothesis of attenuated COL1 degradation being the key driver of fibrosis and a major contributor to onset and progression of CDs. This will be achieved through multi-disciplinary research and training combining state-of-the-art –omics approaches and data (peptidomics, proteomics and transcriptomics) in a bioinformatics framework, followed by in- and ex-vivo investigation, complemented with ESRs training on translational skills and competences. Such a programme will train a new generation of translational researchers able to covert ideas into products, and will have a profound impact on their employability, and competitiveness. The project will progress beyond the state of the art and provide the currently missing fundamental knowledge on the molecular pathophysiology of COL1 degradation, setting up the stage for novel biomarkers and anti-fibrotic therapies.