Regulation of mammalian genome architecture and mobility in pluripotent and transformed cells

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In this project, we plan to investigate the architecture and mobility of the mammalian genome. It is unclear how the chromatin structure maintenance or reorganization during the cell cycle, cellular differentiation affects or is affected by chromatin motion. Moreover, there is substantial evidence that chromatin organization and dynamics is altered in tumor cells. We have developed imaging and image analysis methods to analyze genome structures at different resolution levels and corresponding to different hierarchical levels of organization of the genome (DNA loops and topologically associated domains). In parallel, we have generated and characterized cellular systems and will study whether and how chromatin organization and mobility relate with stochastic gene transcription, which are main characteristics of pluripotent as well as oncogene-transformed cells. Hence, we will focus, on the one hand, on cellular pluripotency and loss thereof and, on the other hand, on oncogene-induced cellular transformation. We will develop novel computational methods for image analysis based on deep learning to accurately quantify the chromatin higher-order structures and their mobility based on microscopy images of different cell types 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.