Modelisation of structural properties and conformational dynamics of LOX – 2017

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, [e-mail], 03 80 39 59 22
Prof. Manuel DAUCHEZ : supervisor, [e-mail]