Thermodynamic bases of thermogenesis by quantum chemistry and kinetic modelling

Context

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.

Project

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.

Profile

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).