SINGER · Stochastic dynamics of sINgle cells: Growth, Emergence and Resistance

This project aims to introduce new stochastic and deterministic models for biological and medical applications, to analyse them mathematically, to derive qualitative properties of solutions, to quantify the emergence of asymptotic regimes and to determine the limiting equations. Motivated by recent biological experiments involving single cell observations, we emphasize the effects of very small populations in various biological/medical contexts related to evolution such as emergence of leukemia and of antibiotics resistance. Our main mathematical challenge is to quantify such effects in particular on macroscopic approximations. It is our hope that this will possibly shed some light on new therapeutic strategies. In order to track individuals and to take into account small populations, we are naturally led to stochastic multiscale models while the limiting macroscopic equations should involve nonlocal nonlinear partial differential equations (PDE) with constraints and singularities. We shall investigate in particular the impact of various time scales on macroscopic approximations of a new class of birth and death processes leading to a new class of Hamilton-Jacobi (HJ) equations with constraints and singularities. Preliminary numerical simulations indicate that these models should exhibit many surprising asymptotic behaviours such as cyclic behaviours that we shall attempt to derive rigorously. We also plan to study the lineages of sampled individuals at a given observation time by determining mathematically their time reversal paths. This issue is of particular relevance when taking into account the effect of time dependent environments, in which case the survival of individuals may only be explained by a very small number of initial individuals. One long term objective consists in imagining evolutionary scenarii of resistances and better strategies for antibiotics or chemotherapy. It will be closely developed with biologists and medical biologists.