Section: Overall Objectives

Evolution of research direction during the last evaluation

1. Multi-scale modeling of erythropoiesis, the process of red blood cell production, in order to describe normal, stress, and pathological erythropoiesis, using mathematical and computational models. This led to:

2. The modeling of hemoglobin instability in dialysis patients: Thomas Lepoutre has been progressively taking part in this theme through a collaboration with P. Kim (University of Sydney, Australia);

3. Multi-scale modeling of the CD8 T cell immune response, in order to develop a predictive model of the CD8 T cell response, by confronting the model at different stages to in vivo-acquired experimental data;

4. Population dynamics modeling, with the aim to develop general mathematical tools to study them. The main tools we were using were structured equations, in which the cell population is endowed with relevant structures, or traits. We identified limitations in using these formalisms, this is why we started developing multi-scale approaches;

5. Modeling of Chronic Myeloid Leukemia (CML) treatment, using ordinary differential equations models. Our team had already developed a first model of mutant leukemic cells being resistant to chemotherapy. A next step would be to identify the parameters using experimental data;

6. Multi-scale modeling carried out on the basis of hybrid discrete-continuous models, where dissipative particle dynamics (DPD) are used in order to describe individual cells and relatively small cell populations, partial differential equations (PDE) are used to describe concentrations of bio-chemical substances in the extracellular matrix, and ordinary differential equations for intracellular regulatory networks (Figure 1). An emphasis would be made on developing codes that are both flexible and powerful enough to implement variants of the model, perform simulations, produce desired outputs, and provide tools for analysis; to do so:

7. We planned to contribute to a recent project named chronos, whose code (written in C++) represents heterogeneous populations of individual cells evolving in time and interacting physically and biochemically, and the objective is to make the code flexible enough to implement different formalisms within the same model, so that different components of the model can be represented in the most appropriate way;

8. Partial differential equations (PDE) analysis, with a focus on reaction-diffusion equations, transport equations (hyperbolic PDEs) in which the structure can be age, maturity, protein concentration, etc., with particular cases where transport equations are reduced to delay differential equations (DDE).