Regulation of mammalian genome architecture and mobility

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In this project, we plan to investigate the architecture and mobility of the mammalian genome. We and others have shown that different levels of organization of the genome can be visualized during duplication of the genome as replicons and clusters thereof, likely corresponding to DNA loops and Mbp topologically associated domains (TADs), respectively. This will now allow us to investigate how different epigenetic states and different subnuclear spatial localization patterns impact genome architecture and mobility. We will additionally compare data from different cell types and mammalian species, pluripotent versus somatic cells, and will probe potential regulators using cells deficient on known epigenetic/chromatin factors or pharmacological inhibition. Finally, we will investigate whether genome mobility is affected by genome metabolism. Novel computational methods for automated image analysis based on deep learning will be developed for accurate quantification of the chromatin higher-order structures and their mobility based on microscopy data at different resolution levels. This work should provide insights on the organization and mobility of the mammalian genome and how this regulates or is regulated by genomic processes.