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Exploring the genomic complexity of bacterial infection in 3D

Abstract : Numerous bacteria and viruses use cells from another species to ensure their proliferation. This mode of reproduction implies the pathogen must escape the host immune system and reprogram its metabolism to sustain its own needs. These changes are often detrimental to the host cell and cause pathologies or death. The intracellular bacteria which use this mode of operation have been the focus of many studies aiming to understand their "hijacking" mechanisms. Recent advances in genomics have largely stimulated research in this field by offering the possibility to decipher the sequence of genes expressed during infection. Several intracellular bacteria secrete "effector" proteins into the host cytoplasm which interact with its proteins and affect its genetic expression program. Recently, studies in Legionella pneumophila, an experimental model for intracellular bacteria, have shown it was able to alter the epigenetic state of its host. Such modifications allow rapid physiological changes and are intimately linked to the spatial organisation of the genome. 3D genome organisation plays an important part in many biological processes, for example by modulating gene expression through long range interactions in the sequence. Throughout this work, we develop computational tools to explore and measure spatial changes occuring in the genome, and exploit them to investigate the changes taking place during infection by intracellular bacteria. We use the model species Legionella pneumophila and Salmonella enterica to explore structural changes taking place in the host chromosomes and their link with genetic expression.
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Submitted on : Wednesday, May 25, 2022 - 5:33:13 PM
Last modification on : Tuesday, May 31, 2022 - 4:08:21 PM

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  • HAL Id : tel-03679023, version 1

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Cyril Matthey-Doret. Exploring the genomic complexity of bacterial infection in 3D. Genomics [q-bio.GN]. Sorbonne Université, 2021. English. ⟨NNT : 2021SORUS346⟩. ⟨tel-03679023⟩

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