Thèse en modélisation moléculaire [Aout 2014]

P { margin-bottom: 0.08in; }A:link { }

Molecular modeling study of the activation of transmembrane receptors involved in chemical senses

Advisor: Serge Antonczak / Sébastien Fiorucci

email: Serge.Antonczak@unice.fr , Sebastien.Fiorucci@unice.fr

Laboratory: Institut de Chimie de Nice, UMR 7272 CNRS.

Starting date: September 2014

Keywords: Molecular dynamics, homology modeling, docking, GPCR, chemical senses.

PhD thesis will take place at the 'Institut de Chimie de Nice', UMR 7272 CNRS, in the team 'Arômes Parfums Synthèse et Modélisation'. APSM team works long on the chemical diversity of odorants : analysis and valorization of natural compounds, synthesis of new odorants, description of molecular mechanisms involved in chemical senses. The research project is linked to the research theme « Odorant-Odor-Olfaction » supported by the Nice Sophia Antipolis Université and the CNRS and will focus on the interactions between tastants and odorants within our taste and olfactory system.

Smell and taste are two chemical senses intertwined. The response of our organism, whether voluntary or not, taking in food is tightly influenced by both senses. The taste intensity of a nutriment, its hedonic properties, or our psychophysical response can be regulated by the simultaneous perception of an odor. The description of the physiological phenomena related to the detection of odors and tastes is essential for understanding the interaction between these chemical senses. This long-term project aims to better understand this intersensoriality.

At the physiological level, the taste and smell perception consists of chemical stimulation of the olfactory and gustatory receptors on the surface of the sensory cells. These transmembrane receptors belong to the G protein-coupled receptor (GPCR) family, for which very few experimental structures are solved. Molecular modeling is perfectly suited to provide relevant three-dimensional structures and to gain insights on the recognition of odorant and/or tastant compounds by receptors involved in chemical senses. The research project will focus on the study of taste receptors, the one involved in sweet taste. Extracellular proteins may regulate GPCR activation and their role will also be explored.

Initial GPCR models will be prepared using state of the art homology modeling and/or ab initio methods. Protein-protein docking at a coarse grained resolution will be performed to predict GPCR-'sweet proteins' modes of interactions. To depict GPCR dynamics, enhanced sampling MD reaching microsecond time scale will be performed.

The candidate must have obtained a master's degree in chemistry, physics or biology and should be familiar with molecular modeling techniques. Knowledge of scientific computing under Linux OS and programming skills are clearly a plus. The candidate will work in a collaborative environment with research teams in cell biology.

More details on: www.unice.fr/icn/fiorucci

Selected references :

[1] J. Golebiowski, L. Charlier, J. Topin, S. Fiorucci, S. Antonczak. Flavour Sciences, 2013, 519-524.

[2] L. Charlier, J. Topin, C.A. de March, P.C. Lai,C.J. Crasto,J. Golebiowski. Methods Mol Biol, 2013, 1003, 53-65.

[3] L. Charlier, J. Topin, C. Ronin, SK. Kim, WA. Goddard III, R. Efremov, J. Golebiowski. Cell Mol Life Sci, 2012, 69, 450-457.

[4] J. Golebiowski, S. Fiorucci, M. Adrian-Scotto, J. Fernandez-Carmona, S. Antonczak. Mol. Inf., 2011, 30, 410-414.

[5] S. Fiorucci, M. Zacharias, Proteins, 2010, 78, 3131-3139.