Evolution of enzyme concentrations in metabolic networks

Evolution of enzyme concentrations in metabolic networks

By In PhD proposals 2018 On April 4, 2018

Project: Evolution of enzyme concentrations in metabolic networks

Laboratory: Génétique Quantitative et Evolution – Le Moulon (GQE)

Affiliation: INRA – Université Paris Sud – CNRS – AgroParisTech
Address: Ferme du Moulon. 91190 Gif-sur-Yvette, France

LAB Director
Name: Olivier C. Martin
Phone number: +33(0)169332336

Name: Christine Dillmann
Phone number: +33(0)169332348

Subject Keywords: Evolutionary systems biology, metabolic control theory, fitness, modeling, computer simulations
Summary of lab’s interests: The lab GQE leads research in genetics, genomics and evolution of complex traits, focusing on integrative approaches. This multi-scale approach relies on methodological developments in modeling, bioinformatics, population genetics, selection methods, systems biology and proteomics (the lab hosts the IBiSA platform PAPPSO). In this context, the scientific goals of the lab are:
– Providing knowledge in fundamental multifactorial genetics in the fields of (i) modeling quantitative variation, (ii) evolution of quantitative traits, (iii) search for genes with quantitative effects and (iv) dynamics of genetic resources.
– Improving plant breeding methods by combining genomics and genetic resources management.
Project summary: Among the components of fitness, metabolic fluxes play a central role. Many studies in evolutionary genetics have focused on polymorphism and evolution of genes that impact enzyme properties, but the interpretation of the observations are elusive because they never rely on any theoretical framework. The main difficulty for modeling comes from the non-independence of enzymes, due to (i) the summation property of the flux control coefficients, (ii) the cost of protein synthesis that results in trade-offs and (iii) the existence of regulatory mechanisms. The goal of this PhD project is to develop a theoretical model for enzyme evolution taking these factors into account. The starting point will be a differential equation system describing the variation of enzyme properties when there is selection on the flux. This tool will permit to search analytically the equilibrium values of enzyme kinetic parameters and concentrations. The predictions will be confronted with the results of simulations of long-term flux evolution performed on (i) virtual networks of Michaelian enzymes, (ii) real systems described by differential equation systems (e.g. glycolysis and published complete networks of central metabolism of microorganisms). Finally meta-analysis will be done to compare the predictions with actual values of enzyme kinetic parameters and concentrations.
Interdisciplinary aspect of the project: The PhD project in theoretical biology is clearly at the interface of mathematics (developing a framework for enzyme evolution using dynamical systems), biology (evolutionary genetics and metabolism) and bioinformatics (simulations, meta-analysis). Thanks to collaboration with Arnaud Le Rouzic (CNRS, EGCE lab, Gif-sur-Yvette), it will help reinforce theoretical biology within the IDEEV (Institut Diversité, Evolution et Ecologie du Vivant, Orsay-Gif-sur-Yvette).
Funding: None.