Séminaire interne : Fabrizio Cleri
Séance du jeudi 25 septembre 2014, 12:15 - 14:00,
Salle du conseil de l'UFR de Physique (Bat P5bis, 252)
Theory and modelling of DNA mechanics and radiation damage
Fabrizio Cleri
Institut d'Electronique, Micro-Electronique, et Nanotechnologies (IEMN)
The mechanics of DNA in its various forms is today a largely studied subject, with relevance both for fundamental research and applications, as well for its technological implications. In our group at IEMN Lille, we started a collaboration merging basic science (physics, chemistry, biology) with applications (engineering, medicine, radiotherapy), aimed at unravelling the relationships between DNA damage, biological effect and, ultimately, clinical outcomes, notably in cancer therapy. DNA double-strand breaks (DSB) are recognized as the most toxic DNA lesion since they threaten the genome integrity. Ionizing radiations are major inducers of DSB, either by direct ionization, or by generation of reactive oxygen species in the cytoplasm. On the other hand, DNA single-strand breaks (SSB) are a major mutagenic damage resulting from oxidative stress. In Lille we perform in-vitro micromechanical-microfluidics experiments on DNA bundles irradiated by high-energy photon beams, and in-vivo irradiation on cell cultures with fluorescence spectroscopy and comet assay to detect SSB and DSB. In both cases, the objective is to correlate the macroscopic effect of ionizing radiation to molecular-scale damage induced in DNA and chromatin. Here I will present the efforts done in theory and simulation of DNA damage by ionizing radiation, with three parallel programs complementing and integrating our in-vivo and in-vitro experimental work: 1) statistical-mechanics theory and modelling of single-molecule and many-molecule dynamical force experiments; 2) nanomechanics of DNA i-motif tetraplex; 3) molecular dynamics of damaged DNA short strands and ionic effects.