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Leo Darrigade : Modelling G protein-coupled receptors (GPCRs) compartmentalized signaling

G protein-coupled receptors (GPCRs) are membrane receptors that play a pivotal role in the regulation of reproduction and behavior in humans. Upon binding to specific ligands, they trigger a local cAMP production. Activated receptor are then internalized to different endosomal compartments where they can continue signaling before being recycled or destroyed. Recent studies showed that the different pools of cAMP have different effect on the cell.
In the first part of the talk, I will present a piecewise deterministic Markov process (PDMP) of intracellular signaling. The stochastic part of the model accounts for formation, coagulation, fragmentation and recycling of intracellular vesicles which contain the receptor, whereas the deterministic part of the model represents evolution of chemical reactions due to signaling activity of the receptor. We are interested in the existence of and convergence to a stationary measure. I will present different cases for which we were able to obtain results in this direction.
In the second part of the talk, I will present the numerical workflow (SBML, PEtab and PyPESTO) we use to fit ODEs model of GPCR signaling to longitudinal measure of chemical concentrations (BRET data).

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