PhD position (M/F) - Modeling Overflow Metabolism

Job Description

Thesis Subject

Topic:
Microorganisms such as bacteria and yeast often exhibit overflow metabolism, a behavior in which fermentation and respiration coexist even under nutrient-rich and oxygen-abundant conditions. This leads to the secretion of partially oxidized by-products (e.g., acetate, ethanol), despite the availability of more efficient metabolic pathways [1-3].
Understanding why cells adopt such apparently suboptimal strategies is a fundamental question at the interface of physics and biology. It raises the broader issue of how thermodynamic, kinetic, and stoichiometric constraints jointly shape metabolic organization [4-6].
This PhD project aims to develop a quantitative modeling framework to investigate the emergence and regulation of overflow metabolism. The project will combine stoichiometric, kinetic, and thermodynamic approaches to analyze how energetic constraints and dissipation shape metabolic flux distributions, how different control mechanisms such as proteome allocation, enzymatic limitations, and thermodynamic driving forces can be integrated within a unified framework, and how overflow metabolism emerges and evolves during transitions between by-product secretion and re-assimilation. The case-study model and associated data focus on acetate overflow in E. coli, in collaboration with the Toulouse Biotechnology Institute.

References:
[1] Basan et al., Nature 528, 99 (2015); [2] Millard et al., EMBO J 42, e113079 (2023); [3] Gosselin et al., Mol Syst Biol 21, 1419 (2025); [4] Yang et al., PNAS 118, e2026786118 (2021); [5] Pfeuty, Biophys J 123, 3600 (2024); [6] Cossetto et al., Nat Commun 16, 8543 (2025).

Candidate profile:
We are seeking a candidate with a Master's degree in physics, biophysics, or systems biology, with Python skills and a solid background in quantitative methods (linear algebra, dynamical systems, and statistics). The candidate should have a clear interest in biological systems. An interest in thermodynamics of living systems, some knowledge of metabolism or omics data (or willingness to learn), and an ability to work at the interface between theory and data will be considered a plus.

Your Work Environment

The project is interdisciplinary, combining theoretical modeling, computational methods, and data analysis. The candidate will:
• develop/analyze models of metabolic networks grounded in flux balance and non-equilibrium thermodynamics frameworks, using programming tools (primarily in Python)
• interact with metabolomics and fluxomics datasets provided by partner group (METASYS team at Toulouse Biotechnology Institute)

The PhD will be carried out at PhLAM (CNRS, University of Lille), which offers a structured doctoral training program and a prime location with easy access to Brussels, London, and Paris.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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