The PrionSpace project aims to study the multiscale mechanisms governing prion dissemination and its impact on neuronal network function. The central scientific questions addressed in this project are: (1) How do antagonistic catalytic mechanisms that govern prion assembly at a molecular level translate into strain-specific spatial dissemination patterns within brain tissue ? (2) How do tissue anisotropy, neuronal activity, and stress responses regulate prion replication dynamics ? (3) How do these physical and biochemical processes lead to functional degradation of the neural network ?
To answer these questions, PrionSpace integrates mathematical modeling, statistical inference, and experimental validation. It will develop a multi-scale modelling framework coupling growth–fragmentation kinetics with reaction–diffusion equations in order to describe prion dissemination in neural tissue. Simulation-Based Inference (SBI) methods will be designed to infer key parameters from experimental data and quantify uncertainties. Finally, electrophysiological data from prion-infected organotypic slices will be used to link aggregate distribution to network-level dysfunction.