Mots-Clés

Tropical disease, Epigenetics, ChIP-seq, RNA-seq, histones, macrophages

Description

Buruli ulcer is a neglected tropical disease caused by the Mycobacterium Ulcerans. In Human and without treatment, 95% of the patients displayed severe skin ulcerations, the remaining 5% presented spontaneous cicatrization of the lesions.

To explain the different responses to the infection, two mouse models mimicking the human symptoms were identified and have shown that an initial contact to M. Ulcerans toxin affects the response of macrophages to subsequent exposure to that toxin, a process called immune training. We aim to test the hypothesis that such immune training by M Ulcerans is mediated by epigenetic changes to macrophages, specifically modification to histones. To that end we have carried out ChIP-seq analysis of various modified histones distribution (H3K4me3, H3K4me1, H3K9me3, H2A.Z, H3K36me3) as well as RNA-seq analysis of the transcriptome, during the immune programming process.

The successful candidate will characterize changes to these histone modifications distribution and evaluate correlation with changes to the transcriptome. The outcome of the internship will be the production of a list of genes and associated modified histone loci that are candidate for a role in the immune programming of macrophages by M. Ulcerans.

The internship will take place at the CR2TI lab at Nantes Hospital, within an interdisciplinary environment. A knowledge of NGS data processing and basic bioinformatic skills (R, Bash…etc) is required. Good communication and presentation skills are necessary. The candidate will work in close collaboration with a PhD student that will assist in implementation of ChIP-seq and RNA-seq analysis pipeline.