Revenir à la liste des offres d'emplois Understanding formation and repair of 8-oxoG damages in the nucleosomal DNA atomic simulation Stage · Stage M2 · 6 mois Bac+5 / Master Laboratoire de Chimie ENS de Lyon · Lyon (France) Date de prise de poste : 8 janvier 2024 Mots-Clés DNA repair, Nucleosome, Molecular Dynamics, Description Light, oxidative stress or exogenous molecules can modify the well-designed structure of DNA by inducing nucleobases lesions. The accumulation of these damages can hinder the DNA transcription or replication and lead to mutations, cell apoptosis or cancers. As a consequence, numerous studies focus on the elucidation of the mechanisms of damages formations or their repair by dedicated proteins. Because of the complexity of the DNA molecule in its biological context, the problem becomes rapidly combinatorial, involving sequence, structural and dynamical effects. Indeed, beyond the double strand structure, the DNA polymer is wrapped around a core of eight proteins call histones to form nucleosomes.[1] This specific and dynamical environment mechanically constrains the DNA conformation and creates an heterogeneous electrostatic field, which impacts the physicochemical properties of the nucleobases, their reactivity and their accessibility to protein interacting with DNA. In this project, we focus on the 8-oxoguanine damage which results from the oxidation of a guanine. This damage is known to modify the DNA conformation, and also to evolve to secondary damages and abasic sites because of its redox properties. On the other hand, it is recognized by several proteins such glycosylases for its repair. We thus plan in this project to use classical molecular dynamics simulations to explore the conformational behavior of the 8-oxoguanine in the context of nucleosomal DNA its possible interaction with repair proteins. These methods have been successfully used in our group for simulations of damaged nucleosomal DNA [2-4] and of glycosylase-damage DNA interaction [5]. We aim to go further in the analysis of the combinatorial mechanisms at play in the damage behavior in the nucleosomal DNA environment by inclusion of dedicated machine learning approaches. This project is part of a collaboration with an experimental group at IAB, Grenoble, to propose a repair mechanism hypothesis involving different proteins. The simulations performed during this master will be helpful to decide which damaged sequences will be selected for the experimental and computational studies of protein and nucleosome interplay. The candidate must have a background and/or interest in physical chemistry, biochemistry or molecular biology. Competences in programming, computational chemistry or bioinformatics are also welcomed. PhD application is open in the continuation of this master project. Candidature Procédure : Send a CV with a covering letter by mail Date limite : 15 décembre 2023 Contacts Natacha Gillet naNOSPAMtacha.gillet@ens-lyon.fr Offre publiée le 11 septembre 2023, affichage jusqu'au 15 décembre 2023