PRE2023-Coordinación entre la replicación y la transcripción del genoma con el metabolismo y la plasticidad celular (PID2022-141380NB-I00)

DNA replication and transcription are two essential processes that share the same chromatin template. The evidence accumulated over the past decade, including our work, has unveiled the complex relationship between them and the chromatin structure, essential to maintain genomic stability. In this project we want to push forward this notion of mutual interdependence by integrating replication-transcription coordination with cellular metabolism and fate determination. This knowledge is highly relevant for basic biology, but it is also key to understand disease scenarios where this coordination can go awry, such as in certain developmental syndromes or pathologies like cancer. We have designed a research program that combines a range of multidisciplinary state-of-the-art approaches, from multi-omics to super-resolution imaging, chromatin conformation capture, genomic editing and machine learning. By this we aim at gaining a molecular understanding of how the replication-transcription crosstalk modulates chromatin structure in two key cellular processes: cellular plasticity and stress responses. The knowledge generated might be specially relevant in the field of cancer, where cellular de-differentiation and replicative stress induced by transcription dysregulation are hallmarks.