Olivier Silvie MD and PhD Biochemistry and Molecular Biology

Course and current status

Since 01/2014: Team leader "Molecular biology and immunology of malaria liver infection", Centre d'Immunologie et des Maladies Infectieuses (CIMI), INSERM U1135, Université Pierre et Marie Curie, Paris, france

Since 09/2013: Affiliate member of the EVIMalaR european Network of Excellence

Since 03/2012: Member of the Laboratory of Excellence ParaFrap

10/2010-12/2013: Inserm CR1 Research Associate, Inserm/UPMC UMR_S945, Paris, France

01/2009-09/2010: Postdoc, Max Planck Institute for Infection Biology, Berlin, Germany (EMBO Long-Term Fellowship)

09/2006-12/2008: Postdoc, Heidelberg University School of Medicine, Heidelberg, Germany (Marie Curie Intra-European Fellowship)

11/2001-08/2006: PhD in Biochemistry and Molecular Biology, Inserm U511, University Pierre et Marie Curie Paris 6, Paris, France (Inserm Poste d'Accueil)

10/1996-10/2001: Intern in Medical Biology, Paris, France

10/1989-09/1996: Medical Studies, University René Descartes Paris 5, Paris France

Scientific summary

Molecular mechanisms of malaria liver infection.

Plasmodium parasites, the causative agents of malaria, are transmitted by Anopheles mosquitoes, which inject motile forms termed sporozoites in the skin. In the first hours of infection, sporozoites migrate in the skin, enter the blood circulation and travel to the liver. There, sporozoites invade hepatocytes inside a specialized compartment, the parasitophorous vacuole. Inside the vacuole, the parasite replicates and differentiates into thousands of merozoites. Once released in the blood circulation, merozoites infect erythrocytes and initiate the clinical phase of infection, associated with the symptoms and complications of malaria.

Infection of hepatocytes by Plasmodium sporozoites is an essential and clinically silent phase of the parasite life cycle, and therefore constitutes an ideal target for anti-malarial prophylactic approaches, notably vaccines. Our group study the molecular mechanisms involved during infection of the liver by Plasmodium. Our projects focus on two aspects: host cell invasion and regulation of gene expression in Plasmodium sporozoites.

The molecular mechanisms of host cell invasion by Plasmodium sporozoites remain unknown. According to the current model, entry into host cells occurs through a tight junction formed by parasite ligands bound to host receptors, which have not been identified yet. The parasite propels itself actively through the junction to enter the cell inside a vacuole. Our objective is to identify parasite and host molecules involved during sporozoite invasion of hepatocytes. In particular, we study the role of CD81, a transmembrane protein expressed at the surface of hepatocytes that is required for Plasmodium sporozoite invasion.

We are also interested in regulation of gene expression during Plasmodium transmission from the mosquito vector to the mammalian host. We investigate transcriptional and post-transcriptional regulatory mechanisms controlling expression of parasite factors that are required during Plasmodium liver stage development. In particular, we study the role of SLARP, a key regulator of sporozoite gene expression, and the post-transcriptional regulation of UIS4, an essential protein of the parasitophorous vacuole membrane.

Our long-term goal is to improve our understanding of the mechanisms of Plasmodium sporozoite invasion and differentiation, in order to develop novel prophylactic approaches against malaria liver infection.

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