This project studies how fibroblast activity can be modulated by functional epigenetic perturbation (CRISPRi) of active distal regulatory elements (enhancers). P02 will characterise the epigenome of quiescent and activated fibroblasts to identify enhancer elements involved in fibroblast activation. Chromatin interaction analysis will uncover the respective enhancer target genes. P02 will perform CRISPRi single cell screens to assess the regulatory potency of identified enhancers in vitro. Perturbation of selected enhancers will be optimised and tested for their potential to modulate cardiac fibrosis formation in post-myocardial infarction lesions in vivo. To ensure the translational perspective, conservation of enhancer function will be confirmed in cardiac fibroblasts from different species.