Objective Cell fate conversion processes bear considerable therapeutic potential yet are poorly understood, and have thus remained slow, inefficient and difficult to translate into medical applications. The low conversion frequency in current systems, such as classic reprogramming to ‘induced’ pluripotent stem (iPS) cells, has precluded a molecular study of the critical early conversion events. We propose an interdisciplinary, exhaustive and unbiased approach to unravel the molecular events that accompany cell fate conversion processes, in particular during the early phase, using two uniquely efficient and controllable experimental systems. Special emphasis will be put on documenting the dynamics of three-dimensional genome topology, as this potential epigenetic conversion barrier has not yet been systemically characterized during cell fate conversions. We will apply genome-wide chromosome conformation capture and other genomic technologies on B cells undergoing nearly 100% efficient transdifferentiation into macrophages or reprogramming into iPS cells. In-depth computational analyses and dataset integration will reveal the dynamic relationships between transcription factor binding, key epigenetic regulatory mechanisms including genome topology, and the gene expression changes that ultimately lead to the implementation of a new cellular phenotype. Acquiring such insights will signify a breakthrough in our understanding of the epigenetic features that underpin cell identity and plasticity. Besides significantly advancing the state-of-the-art, the proposed action will maximize the applicant’s capacity of reaching professional maturity and scientific independence. Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesmathematicspure mathematicstopologynatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesgeneticsepigenetics Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2014 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator FUNDACIO CENTRE DE REGULACIO GENOMICA Net EU contribution € 158 121,60 Address CARRER DOCTOR AIGUADER 88 08003 Barcelona Spain See on map Region Este Cataluña Barcelona Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 158 121,60