Section: New Results

CRN modeling of biological systems

Participants : Auriane Cozic, Elisabeth Degrand, François Fages, Eléa Greugny, Jeremy Grignard, Constance Le Gac, Léna Le Quellec, Paul Remondeau, Sylvain Soliman.

This year, beyond implementation work on hybrid simulations in BIOCHAM and on antithetic feedback control in CRNs, we have started the computational modelling of three biological systems with important potential applications in biomedicine.

The first is about erythrocytes (i.e. red blood cells). Their most obvious function concerns the respiratory system since erythrocytes allow gas exchanges at the level of the organism by transporting dioxygen and carbon dioxide between the lungs and the tissues. However, red blood cells also have an important buffer function in the blood, which is necessary to keep blood pH in the physiological range. Modelling the red blood cells with CRNs using BIOCHAM gives us insight as to which biological objects are necessary to allow the cell to process its functions correctly. At the level of Systems Biology, it also allows us to understand the links between the different biological functions of erythrocytes.

The second concerns microtubules and their post-translational modifications involved in major cellular processes such as: mitosis, cardiomyocyte contraction, and neuronal differentiation. More precisely, in neurons, the post-translational modifications of detyrosination and tyrosination are crucial for neuronal plasticity, axon regeneration, recruitment and transports of proteins and correct neuronal wiring. We hypothesize that the decrease of density and length of microtubules and the loss of neuronal structures such as synapses, dendritic spine and growth cone which are correlated with the progressive cognitive decline [9,10] may be the consequence of the dysregulation of the cycle detyrosination/tyrosination in neurodegenerative disorder. This hypothesis is investigated in collaboration with Servier by combining experimental approaches with mathematical modelling.

The third concerns inflammation processes in skin. Skin protects the body against external agents, for instance pathogens, irritants, or UV radiation, that can trigger inflammation. Inflammation is a complex phenomenon that is classified in two main types, acute and chronic. They are distinguished by different parameters such as the duration, the underlying mechanisms, the components involved like the type of immune cells, and the nature and intensity of the associated clinical signs. The computational models developed in collaboration with Johnson&Johnson France, combine mathematical and multi-agent modelling using BIOCHAM and EPISIM modelling tools.