CV Science

Olivier Silvie MD and PhD Biochemistry and Molecular Biology

Course and current status

Current position

• Deputy Director Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris, directeur C. Combadière), U1135, INSERM, Sorbonne Université, CNRS.
• Team leader "Biology and immunology of malaria", Centre d'Immunologie et des Maladies Infectieuses , INSERM U1135, UPMC UMRS CR7, CNRS ERL8255, Paris, France (since 2014).

Education

• Research Management Certification (Habilitation à Diriger des Recherches, HDR), Université Pierre et Marie Curie, Paris, 2011
• PhD in Biochemistry and Molecular Biology, speciality Microbiology-Parasitology, Université Pierre et Marie Curie, Paris, 2006
• Medical Doctorate, Université René Descartes, Paris, 2003
• Diploma of Specialized Studies (DES) in Medical Biology, Université René Descartes, Paris
• Master Degree, Microbiology-Virology, Université Pierre et Marie Curie, Paris, 2000

Scientific networks

• Member of the LabEx Parafrap (French Parasitology Alliance for Health Care), since 2012
• Member of PalSud Consortium (Aviesan, I3M), member of the steering committee, since 2014
• Member of FP7 Consortium PathCo (Pathogen Co-infection: HIV-1, Tuberculosis, Malaria and hepatitis C virus), 2012-2017
• Affiliate member of the FP7 Network of Excellence EVIMalaR (European Virtual Institute of Malaria Research), 2013-2015

Past positions

• 2010-2013: INSERM UMR_S 945, Immunité et infection, Dir. Prof D. Mazier, Paris, France (CR1 Inserm)
• 2009-2010: Max Planck Institute for Infection Biology, Parasitology Unit, Dir. Dr K. Matuschewski, Berlin, Allemagne (PostDoc, EMBO fellowship)
• 2006-2008: Heidelberg University School of Medicine, Department of Parasitology, Dir. Prof M. Lanzer, Heidelberg, Allemagne (PostDoc, Marie Curie fellowship)
• 2002-2006: INSERM U511, Dir. D. Mazier, Paris, France (PhD, Poste d'Accueil Inserm)
• 1999-2000: INSERM U511, Dir. D. Mazier, Master student (FRM fellowship)
• Hospital residencies, Medical Biology (1996-2001): Microbiologie (Hôpital Broussais), Biochimie (Hôpital Saint-Joseph), Hématologie (Hôpital Curie), Parasitologie (Hôpital Saint-Louis), Parasitologie (Hôpital Pitié-Salpêtrière), Maladies Infectieuses (Hôpital Pitié-Salpêtrière), Virologie (Hôpital Pitié-Salpêtrière) and Immunologie (Hôpital Pitié-Salpêtrière).

Teaching responsabilities

• Co-supervision of Master M2, speciality Microbiology, Parasitology- Mycology, UE 5V641: Biologie moléculaire et cellulaire des agents infectieux et de la cellule hôte, Université Pierre et Marie Curie, 20h/year since 2011
• Master M2, UE 5V532 Immunothérapies & Bioingénierie, Université Pierre et Marie Curie, 1h30/year since 2013
• International school Immunological Biotherapies: Concepts and Development (IBCD), Université Pierre et Marie Curie, Icahn School of Medicine at Mount Sinai, Universidade de São Paulo, 1h/year since 2016
• Master M1, UE 4V144 Parasitologie/Mycologie fondamentale et médicale, Université Pierre et Marie Curie, 1h30/year, 2011-2014
• École d'Ingénieurs AgroParisTech, étudiants de deuxième année, Module "Mécanismes et évolution de la pathogénie", Paris, 1h30/year
• PhD director (École Doctorale "Complexité du Vivant", Université Pierre et Marie Curie)
• Supervision of Master students (UPMC, École AgroParisTech)

Expert activities

• Reviewer for peer-reviewed journals (Cell Host & Microbe, Nature Microbiology, eLife, PNAS, PLoS Pathogens, Scientific Reports, Cellular Microbiology, Molecular Microbiology, Infection and Immunity, PLoS One, ...)
• Reviewing Editor for eLife, Academic Editor for PLoS One
• Jury referee for PhD and HDR
• External reviewer for European Research Council, Wellcome Trust, Swiss National Science Foundation, Poland National Science Centre, Instituto de Medicina Molecular, Université Grenoble Alpes, COSSEC Biothérapies (Inserm)
• Member of CoNRS section 27 (2016-2021)

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.