UFR de Physique

Propositions de stages en laboratoire -- M2

Les offres sont actualisées en mai. Par exemple, les offres de stages pour l'année universitaire 2015-2016 seront mises en place en mai 2015, les offres de stages pour l'année universitaire 2016-2017 seront mises en place pour en mai 2016, etc.

Nucleosome dynamics in DNA damage and repair mechanisms

  • Option Finalisée « Physicien des hopitaux » du parcours Physique Biologique et Médicale
  • Laboratoire: Autre (Autre)
  • Responsable du stage: Ralf Blossey (ralf.blossey@googlemail.com, )
  • Co-responsable(s): Fabrizio Cleri (fabrizio.cleri@univ-lille1.fr)
  • Mots clés: DNA molecular biology; radiation damage; molecular modelling

Our project aims at a molecular understanding of the dynamics of nucleosomes under conditions that occur during DNA damage and repair. Nucleosomes are the key compaction units in the structure of chromatin. At the same time they are also the platform for numerous protein-DNA and protein-protein interactions, depending on the specific biological context. The project is developed within the framework of a collaboration among the UGSF/UFR Biologie (dr. R. Blossey), IEMN/Physique (prof. F. Cleri) and University of Galway, Ireland (prof. A. Flaus). Radiation damaged DNA develops a variety of molecular-scale defects, among which double strand breaks, which are of paramount importance in the radiotherapy of cancer. In our project, we study, by way of comparison between the canonical and modified nucleosomes, the structural effects exerted by both the replacement of canonical histones, and the presence of post-translational modifications. Post-translational modifications clearly point the way to protein-protein interactions, which might be affected if the corresponding non-canonical nucleosome is less stable than the canonical one. There is indeed evidence for such a destabilization, however, how this happens precisely at a molecular scale is as of now unknown. This stability analysis will be performed for both the canonical and the non-canonical nucleosome. The next step then is to study the wrapping and unwrapping dynamics of DNA on nucleosomes with Molecular Dynamics simulations for both canonical and noncanonical nucleosomes, with single and double-strand breaks induced at different DNA positions around the nucleosome. We have already generated preliminary data already for the canonical nucleosome, thus providing a proof of principle for our approach. This latter part, mostly biophysical, will be the main subject of the internship. The candidate M2 student should be interested in theoretical modelling of biological processes, and have some background in molecular biophysics and basic biology. Basic/advanced skills in numerical computing should not be a fundamental prerequisite (you will learn everything here with our teams), but are certainly welcome for this project.