2025 Genome Architecture in Cell Fate and Disease Gordon Research Conference and Gordon Research Seminar - Project Summary The goals of this meeting are to cover the latest advances in chromatin structure and long-range gene regulation in normal physiology, in disease and in response to environmental insults, to bring together the international 4D- Nucleome community, to create a forum of learning and discussion, and to inspire future developments and collaborations. We propose an interdisciplinary conference to cover the 4D Nucleome theme across scales of genome regulation, from local chromatin processes involving transcription factors and epigenetic modulators, to the higher-order mechanisms of three-dimensional chromosome folding, and the functional and structural organization of the genome within the cell nucleus. We will especially highlight research that investigates 3D genome architecture across broad disease topics, including cancer, neurodevelopment and neurodegeneration, muscle and hematological pathologies. Past decades have witnessed rapid conceptual and technological progress in deciphering the fundamental mechanisms that regulate 3-dimensional structure of the human genome, including targeted actions such as the NIH Common Funds 4D-Nucleome program. The meeting will address the latest challenges to determine the role of genome structure in development and disease, its interplay with epigenetic and chromatin regulation mechanisms. We aim to foster knowledge transfer between 4D Nucleome and disease modelling experts, stimulate interdisciplinary discussions, identify knowledge bottlenecks and collaborative opportunities. To reveal the complex mechanisms of gene regulation in time and space, major ongoing efforts aim to decode the rich genetic and epigenetic information stored in the genome sequence, to model it using universal physics concepts, and to derive predictive models. We will also highlight innovations in the engineering of genome topology, through optogenetics or other tools that can alter the molecular reorganization of DNA, RNA or proteins in the nucleus. We will highlight exciting advances in chromatin structure analysis with multimodality, such as parallel detection of chromatin accessibility and gene expression, with single-cell resolution and tissue spatial information, with special interest in human-relevant applications. The 4D- Nucleome field is poised to develop actionable strategies for innovative disease diagnosis, prognosis and therapy, and to contribute to precision medicine and to more efficient and impactful strategies for disease inception and therapy. The 2025 GRC/GRS meetings on “Genome Architecture on Cell Fate and Diseases: Probing and Controlling Gene Regulation in Space and Time” will foster exchanges of exciting concepts, new technologies, and interdisciplinary collaborations. We will provide an interactive, diverse, and inclusive forum for trainees and new investigators across interdisciplinary topics, highlighting their research through short talks, poster previews and poster sessions, while promoting networking opportunities with senior expert.
