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In vivo analysis of NALP3, a protein implicated in three dominantly inherited syndromes, using knock-out and transgenic mice models

Objectif

The mechanisms involved in innate immune responses against pathogens are strikingly conserved during evolution. In plants, as well as in mammals, the innate immune system achieves its role of defence against pathogens through the use of specific pathogen r ecognition receptors, all containing a conserved LRR domain involved directly in pathogen-associated molecular pattern recognition. In mammals, transmembrane receptors associated with pathogen recognition are well described, but the existence of intracellu lar pathogen receptors is just emerging, with the recent description of a new family of human intracellular LRR domain containing proteins named CATERPILLER. These proteins are expected to play key roles in immune responses against pathogens, but to date, their roles are still poorly defined. Here, we propose to study one of these putative intracellular pathogen receptor, NALP3, which is implicated in three human dominantly-inherited inflammatory syndromes. We plan to 1) characterise the tissue specificity of Nalp3 expression in mice, and 2) use in vivo models consisting of Nalp3-deficient mice and NALP3 transgenic mice overexpressing the human wild-type or mutated proteins, to gain insight into 2.1) the role of Nalp3 protein in the mouse innate immunity, 2. 2) the mechanisms involved in intracellular pathogen recognition and 2.3) the role of the human NALP3 protein and its involvement in inherited inflammatory disorders.

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Appel à propositions

FP6-2002-MOBILITY-5
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Coordinateur

UNIVERSITY OF LAUSANNE, DEPARTMENT OF BIOCHEMISTRY
Contribution de l’UE
Aucune donnée
Coût total
Aucune donnée