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It is now well accepted that our genome is much more than a passive, one-dimensional, storage unit of genetic information. Advances over the last decade alone have paved new and exciting ways for studying genomes as three-dimensional entities with distinct temporal dynamics. Such studies are helping us explain the overarching architecture of chromosomes and their regulatory plasticity. Nonetheless, this field of study is rapidly evolving and new technologies, new challenges, and new insights into the structure-to-function relationship of genomes emerge every day. As a result, this EMBO Workshop will bring together established and younger experts for four days of focused discussions on (i) the contribution of chromatin topology in homeostasis and disease, (ii) the mechanistic basis of chromatin looping and spatial communication between regulatory elements and genes, as well as on (iii) recent experimental and computational modeling advances for dissecting genomic architecture and its dynamics. Ultimately, we will be seeking to unify and integrate views and data to obtain an updated and coherent appreciation of how chromosomes are folded in order to execute their functions.