Proposition de sujet de thèse – 2017 Title : Modelisation of structural properties and conformational dynamics of LOX protein (Lysil Oxidase) Director of the PhD thesis : Prof. Patrick SENET Laboratoire ICB, UMR 6303 CNRS (INP), UBFC, Dijon Departement: Nanosciences Team: Physics applied to proteins Co-director: Dr. Adrien NICOLAI Director of the PhD thesis : Prof. Manuel DAUCHEZ Laboratoire MEDyC, UMR 7369 CNRS (INSB), URCA, Reims COLLABORATIVE PROJECT The PhD work will be conducted in collaboration with the Université de Reims Champagne Ardenne (URCA) and will be supervised by Profs. Senet and Dauchez in close collaboration with the biochemical group of Prof. Ricard-Blum at the laboratory ICBMS (CNRS UMR 5246 (INC)) in University Lyon 1 and with the photonic group of Prof. Finot at ICB (SERS). CONTEXT LOX is a protein involved in the remodeling of the tumoral micro-environment and in the formation of metastasis. LOX has been identified as a promising target for cancer, cardiovascular diseases, and fibroses. However, a limiting step for the development of new drugs and for understanding the interaction of LOX with other proteins is that the structure and conformational dynamics of LOX are unknown. AIM The project aims to build and validate a structural model of the Lysil Oxidase (LOX) involved in the extracellular matrix formation by using homology modeling (Reims) and multi-scale molecular dynamics simulations (Dijon) and biophysical data (SPR, SAXS, CD, SERS) (Lyon, Reims, Dijon). The student will be in charge of the modelisation part. He will develop an atomistic model and a strategy to simulate the low frequency modes of the LOX enzyme, including the effect of the solvent and of the temperature. EXPECTED RESULTS A realistic model of LOX validated by various experimental data. This model could be used in the future to design new therapeutic molecules for cancer therapy. IDEAL CANDIDATE Master in Physics, Biophysics or Physical Chemistry. A training on the methods used in the research program will be provided to the candidate at the beginning of the PhD thesis. Experience with molecular dynamics and modelisation of biosystems and/or with bioinformatic tools is a plus. CONTACTS : Prof. Patrick SENET: supervisor, [email protected], 03 80 39 59 22 Prof. Manuel DAUCHEZ : supervisor, [email protected]