Mots-Clés

computational biology, quantum chemistry, molecular modelling, metabolism

Description

Our bodies constantly dissipate energy to produce heat and maintain their temperature. This process, called thermogenesis, involves several enzyme-catalyzed chemical reactions. How much these contribute to overall heat production, and how this latter is affected by physico-chemical conditions such as pH, remain unclear. A better understanding of thermogenesis could open the way to novel treatments against metabolic diseases and obesity. We propose a Master’s research project aiming at analyzing the thermodynamics of thermogenesis by combining ab initio quantum chemistry and mathematical modelling. The goal is to develop a kinetic model of enzymatic reactions involved, parametrized by thermodynamic data computed by Density Functional Theory (DFT), namely, reaction enthalpies/entropies and activation barriers. To evaluate these latter, specialized methods for the identification of transition states will be used. Later on, extensions to QM/MM analyses of the reactions in enzyme active sites will be considered. The outcome will be a consistent mathematical model of thermogenesis to predict heat production per cycle, which will be compared to in vitro and in cellulo measurements performed by our experimental collaborators. We are seeking a motivated student with solid programming skills (ideally Python), a taste for interdisciplinary research, and a strong background in theoretical chemistry and/or computational biology. Machine learning skills would be a plus. Interested candidates should send a CV and a 1-page cover letter to Dr Florian Blanc (florian.blanc_at_isa-lyon.fr) and Prof. Christophe Morell (christophe.morell_at_univ-lyon1.fr). This project is part of an interdisciplinary collaboration of biologists, biochemists, biophysicists and chemists within the ANR project ThermoCreatine led by Prof. Gilles Rautureau (Univ. Lyon 1).