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Descriptif
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Context: Inside the cellular nucleus, DNA is tightly packed into a polymer-like structure called chromatin. The 3D organization of chromatin is not random and distinct patterns of contacts between chromatin loci are observed. Recently, we propose and test that such organization is mainly driven in fly by the profile of the local biochemical states (the epigenomic state) along the chromatin through physical contact-interactions. In mammals, it is likely that other mechanisms like interactions with the nuclear membrane or loop extrusion play important roles in chromosome folding.
Objectives: In this project, we aim to develop polymer models and corresponding numerical simulations to better understand the mechanisms behind 3D organization in human cells. Based on our previous works, the student will have to develop models that incorporate the main mechanisms driving chromosome organization and dynamics. Characterization of the phase diagram of the system will help us to understand the importance of each ingredient of the model into the 3D chromatin organization. Quantitative comparisons with experimental data (from our collaborator G. Cavalli, IGH, Montpellier, France) on normal and senescent cells will be performed to test the prediction power of the model.
Expected results: We expect this project to give new insights into the mechanisms controlling the 3D chromosome organization in human. In particular, application of our formalism to senescent cells will allow to better understand aging of nuclear organization that is likely to have a strong impact on gene expression. Moreover, original – yet unexplored - physical effects will arise from such very long heteropolymers leading to new paradigms in statistical and polymer physics.
References: Jost et al, Nucleic Acids Res 42: 9541 (2014). Olarte-Plata et al, Phys Biol 13: 026001 (2016). Imakaev et al, FEBS Lett 589: 3031 (2015).
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