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            <title xml:lang="en">Toxoplasma gondii : Knock-out approaches to study the function of dense granule proteins in the host-parasite interaction</title>
            <title xml:lang="fr">Toxoplasma gondii : approches moléculaires (mutants knocked-out) pour l'étude de la fonction des protéines des granules denses dans l'interaction hôte-parasite</title>
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                <title xml:lang="en">Toxoplasma gondii : Knock-out approaches to study the function of dense granule proteins in the host-parasite interaction</title>
                <title xml:lang="fr">Toxoplasma gondii : approches moléculaires (mutants knocked-out) pour l'étude de la fonction des protéines des granules denses dans l'interaction hôte-parasite</title>
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                <authority type="school">École doctorale chimie et science du vivant (Grenoble ; 199.-....)</authority>
                <authority type="supervisor">Corinne Mercier</authority>
                <authority type="supervisor">Marie-France Cesbron-Delauw</authority>
                <authority type="jury">Marc Block [Président]</authority>
                <authority type="jury">Sébastien Besteiro [Rapporteur]</authority>
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                <term xml:lang="en">Toxoplasma gondii</term>
                <term xml:lang="en">Dense granules proteins</term>
                <term xml:lang="en">Chronic  infection</term>
                <term xml:lang="en">Cyst</term>
                <term xml:lang="en">Host-Pathogène interaction</term>
                <term xml:lang="en">Mutant knocked-Out</term>
                <term xml:lang="fr">Toxoplasma gondii</term>
                <term xml:lang="fr">Proteines de granules denses</term>
                <term xml:lang="fr">Infection  chronique</term>
                <term xml:lang="fr">Kyste</term>
                <term xml:lang="fr">Interaction hôte-Pathogène</term>
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              <p>Toxoplasmosis, which is caused by the intracellular parasite Toxoplasma gondii is characterized by a life-long chronic infection. The parasites replicate inside a parasitophorous vacuole (PV), which evolves into a persistent cyst. The molecular mechanisms governing the differentiation process are poorly characterized. It is known that the dense granules proteins (GRA) are major components of both the PV and the cyst wall, enabling their interaction with the host cells. Using a Prugniaud cystogenic type II strain in which the gra5 gene was invalidated and a combination of cellular and proteomic approaches, we discovered that GRA5 regulates i) the molecular content of the PV, ii) the PV interaction with the host endoplasmic reticulum and iii) host cell homeostasis,that is necessary to ensure the formation of a stable cyst wall.</p>
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              <p>Toxoplasma gondii est un parasite intracellulaire responsable de la toxoplasmose. Lors de l’infection aiguë, le parasite se divise dans une vacuole parasitophore (VP), compartiment d’interactions avec la cellule hôte. La VP se modifie pour former un kyste qui persiste au cours de la phase chronique. Le rôle des protéines de granules denses (GRA) dans ce processus est suggéré par leur abondance dans la VP et la paroi kystique. Par des approches de génétique inverse et de protéomique, le but de ce travail visait à préciser au plan moléculaire, le rôle de la protéine GRA5. En utilisant un modèle de différenciation parasitaire in vitro, l’étude des phénotypes d’un mutant invalidé du gène gra5 a permis de découvrir son rôle clé dans la formation des kystes par le maintien 1/ de l’intégrité de la membrane délimitant la VP en cours de différenciation, 2/ de l’accumulation d’autres composants parasitaires dans la VP et 3/ de son interaction avec le reticulum endoplasmique de l’hôte.</p>
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