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Computational analysis and modelling of regulatory networks controlling embryonic development

Abstract : The development of an embryo derives from the DNA sequence of this organism. Genetic variability gives rise to great morphological diversity, while maintaining a robust general organisation. Mutations present within cis-regulatory regions impact transcription via epigenomic mechanisms. The resulting variability in gene expression can be buffered by tran feedback mechanisms within the regulatory network. The precise organisation of these cis and trans interactions remains difficult to decipher. In order to better grasp the effect of mutations on transcription, I analysed genetic, epigenomic and transcriptomic data in collaboration with the Furlong laboratory (EMBL, Heidelberg). The use of allele-specific data from Drosophila F1 lines enabled to infer direct cis-interactions between the regulatory layers, suggesting a difference in the action of the epigenomic markers H3K27ac and H3K4me3 on gene expression. To better understand the trans impact of the structure of regulatory networks on gene expression, I have built a logical model of the dorsal-ventral axis specification in sea urchin embryo, in collaboration with the Lepage laboratory (iBV, Nice). Multicellular and stochastic analyses permitted to detect key components of the network, including the cross-repression dynamic between Nodal and BMP. To conclude, allele-specific data analysis and logical modelling allowed me to study the mechanisms of transcription regulation from two complementary perspectives.
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https://tel.archives-ouvertes.fr/tel-03534373
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Submitted on : Wednesday, January 19, 2022 - 2:03:08 PM
Last modification on : Thursday, March 17, 2022 - 10:08:43 AM
Long-term archiving on: : Wednesday, April 20, 2022 - 6:42:29 PM

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Swann Floc'Hlay. Computational analysis and modelling of regulatory networks controlling embryonic development. Genomics [q-bio.GN]. Université Paris sciences et lettres, 2020. English. ⟨NNT : 2020UPSLE036⟩. ⟨tel-03534373⟩

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