IMMUNOPRION - Immunological and Structural Studies of Prion Diversity

ImmunoPrion proposal addresses the key words of FOOD-2004-T5.4.5.3:
Investigating the fundamentals of TSE enabling the rational development of detection and control strategies establish what defines a strain and what causes the species barrier effect. TSE strains differ in incubation times, and neuro-anatomical PrPSc deposition. They may propagate through the food chain, and there is currently no EU certified diagnostic procedures for their identification.
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Our first objective is to provide a better definition of prion strains based on the structural characteristics of PrPSc. We will characterize in vitro synthesized PrP complexes and analyse the 3D native configuration of different prion strains in follicular dendritic cells derived from the gut, by high-resolution cryo electron tomography.
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Our second objective is to improve our capacity to predict prion transmission through the species barrier. One project is based on the use of a mouse model stably engrafted with human CD34+ stem cells, leading to a fully reconstituted lympho-reticular system. Backcrossing to transgenic mice will induce somatic expression of Hu-PrP in the CNS, to directly test the invasive properties of various prion strains. Another project will evaluate the role of immune surveillance against xenogeneic PrPSc and the influence of chronic intestinal inflammation.
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The third aim is to understand how complement mediates interactions between the different prion strains and the cells of the host immune system (phagocytes, DC). We will also look at markers of acquired immunity induced by the presence of PrPSc in infected hosts, in order to elaborate protocols for an early diagnosis of prion strains. The role of the SME is to create an interface between our consortium and industrial partners or institutions involved in food security, communication and education. All these objectives are organized around the idea that a rational food safety.