This is a highly interdisciplinary project, involving a consortium with expertise in cancer metabolism, experimental biology, genetics, bioinformatics and mathematical modeling. It takes place in a collaboration between the Unit of Pure and Applied Mathematics of ENS Lyon (Pr E Grenier and Dr H Leman) and the Cancer Research Centre of Lyon (Dr P Martinez and Dr A Vigneron). The candidate’s role will be to develop and optimize deterministic and stochastic models integrating genetic and phenotypic data produced by the consortium. These models will be studied analytically, studying longtime behaviours and properties of population growth, extinction and adaptation. The aim is to infer the evolutionary dynamics of resistance in 3 cellular models differing by their evolutionary properties (genetic instability and phenotypic plasticity) and optimize model-specific therapeutic regimens. All 3 models will be treated with a pair of metabolism-targeting drugs, applied first in isolation then sequentially. Longitudinal readouts from sequencing data and metabolism production at multiple generations will be used to parametrise drug combination mathematical models, so as to fit the data observed in vitro. Finally, mathematical simulations will help optimize treatment regimens of the two drugs according to the evolutionary properties of each model, which will be implemented in murine models by collaborators in the consortium for validation.
The candidate will have to be in possession of a PhD or about to at the start of the contract, and will be required to interact with interdisciplinary collaborators. Candidates with a mathematical/computational background and a genuine interest in cancer evolutionary dynamics are encouraged to apply, even without previous experience with cancer data.