The PrionSpace project aims to study the multiscale mechanisms governing prion dissemination and its
impact on neuronal network function. Despite decades of research, the relationship between prion
replication, strain-specific biochemical properties, and neural dysfunction remains largely unknown. In
contrast to other amyloid diseases, prion dissemination in the brain does not follow the canonical
connectome pathways, suggesting that additional molecular and tissue-level processes shape disease
progression.
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.
Approximate Bayesian Computation (ABC) 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.
By establishing a quantitative link between molecular kinetics of prions, spatial dissemination, and
neuronal activity, PrionSpace will provide an original mechanistic understanding of how prion strains
induce neurodegeneration, and lay the foundations for predictive models capable of guiding future
therapeutic strategies.