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Wolfram Liebermeister wolfram.liebermeister@gmail.com INRAE - Unité MaIAGE Domaine de Vilvert 78352 Jouy-en-Josas, France |
DFG-funded research project
"An economic network theory of cell metabolism" (Ll 1676/2-2)
An efficient use of resources such as metabolites, proteins, energy, membrane space, and time is vital for cells. Cells can be studied as economic systems and metabolism is a core component of this system. Mathematical models such as constrained-based, kinetic, and simplified whole-cell models combine knowledge about network structure, thermodynamics, kinetics, enzyme regulation, and allocation of cellular resources. However, these modelling approaches rely on simplifications which limit their accuracy and mutual compatibility. In the project "An economic network theory of cell metabolism", I will develop a unified mathematical theory to study optimal enzyme allocation in cells. The theory, called metabolic economics, extends existing modelling approaches and links them in a new way. The optimality conditions for protein allocation are formulated as economic balance equations, which relate the "economic values" of individual metabolites and enzymes in the network. Metabolic models studied by metabolic economics can be constraint-based or kinetic, and their fitness objectives can score fluxes, metabolite levels, enzyme levels, and cell growth. In addition, I develop a method for flux prediction that combines flux analysis, kinetic modelling, and cost-benefit models of growing cells. I will implement the theoretical concepts and methods in computational workflows, apply them to whole-cell models, and study three biological cases: selection pressures in engineered pathways, the optimal scheduling of enzyme expression in metabolic cycles, and general conditions for symbiosis in bacterial communities. Metabolic economics will extend metabolic modelling, clarify trade-offs between protein investments and metabolic fluxes, and deepen our understanding of enzyme usage in cells.