The three-dimensional (3D) genome organization plays an essential role in all DNA-mediated processes in eukaryotic organisms, including gene transcription, regulation, and replication. Advances in sequencing and imaging techniques have greatly improved its high-resolution characterization, revealing intricate structural features at various scales. Much progress has been made towards unraveling the mechanisms of genome folding and identifying molecular players that affect 3D genome organization in response to different environmental and developmental clues.

Despite the remarkable progress, many questions regarding the genome structure and how the genome folds remain to be addressed. Globally, the genome organization appears to be poised on the border between order and disorder. While many studies have uncovered non-random structural features, the genomic DNA is structurally amorphous and does not adopt a single unique conformation. How specific interactions emerge from a large pool of non-specific contacts is mostly unknown. It is tempting to assume that the genome adopts a similar sequence-to-structure relationship that has been widely accepted for proteins. If so, what exactly are the physico-chemical properties that dictate the genome organization? The answer to this question is not apparent and cannot be simply the genomic sequence of nucleotides. Epigenetic modifications may be the key to forming distinct genome organizations that encode unique gene expression profiles in cells with identical DNA sequences. Equally essential questions arise at smaller scales on the level of single genes (-10 kb). While a seemingly more straightforward problem, mapping the ensemble of 3D structures of a string of nucleosomes remains challenging. There is an ongoing debate regarding whether chromatin adopts the same set of conformations in situ and in vitro. Interactions with protein molecules inside the nucleus may drive chromatin into phase-separated condensates, rendering high-resolution structural characterization challenging due to its dynamic nature. Addressing these questions will improve our understanding of gene regulatory mechanisms, promising to uncover novel genome engineering approaches that will aim to alter the genome organization for more targeted therapeutic approaches.

This workshop will bring both experimental and theoretical experts to discuss the latest developments and the most pressing problems in the exciting field of large-scale genome organization. We strive to promote close collaborations between groups to help interpret experimental results, critically evaluate existing hypotheses, and propose novel theoretical approaches that may inspire new experiments.