Olivier SILVIE

Information

Scientific interests and projects

Scientific interests
Plasmodium sporozoites are transmitted by mosquitoes and first infect the liver for an initial round of replication. Infection of the liver is an essential and clinically silent phase of the malaria life cycle, and thus an ideal target for anti-malarial prophylactic approaches. Building on our expertise in sporozoite and liver stage biology, and our discoveries of host and parasite factors that play key roles during infection, we develop projects exploring the mechanisms of sporozoite entry, liver stage development and hypnozoite formation, and immunity against malaria liver stages. Our goal is to identify new parasite targets for novel intervention strategies targeting the Plasmodium pre-erythrocytic stages.

Scientific activity within ParaFrap
Our first objective is to elucidate at the molecular level host-parasite interactions involved in sporozoite invasion of host hepatocytes (WP1), and to exploit this knowledge to develop new vaccine strategies (WP2). For this purpose, we combine experimental genetics and in vitro cellular models, using both rodent and human malaria parasites. We also use molecular biology and genome editing approaches to explore gene regulation associated with host switching (WP3). Species such as P. vivax produce dormant forms called hypnozoites, which can reactivate and cause malaria relapses. We have developed robust cellular systems for long term in vitro culture of hypnozoites and a humanized mouse model for in vivo studies. These models serve to explore the mechanisms of dormancy (WP1) and to screen for compounds that can kill hypnozoites or activate them for “wake and kill” strategies (WP4). Finally, we are also interested in the role of human T cell immunity against Plasmodium liver stages (WP2). We can provide Parafrap members with our expertise and in vitro and in vivo models, to evaluate antimalarial drugs and vaccines, or to explore fundamental aspects of the parasite biology.

Top 5 publications of the last 5 years

1. Müller K, Gibbins MP, Roberts M, Reyes-Sandoval A, Hill AVS, Draper SJ, Matuschewski K, Silvie O, Hafalla JCR. Low immunogenicity of malaria pre-erythrocytic stages can be overcome by vaccination. EMBO Mol Med. 2021 Apr 9;13(4):e13390. doi: 10.15252/emmm.202013390

2. Neveu G, Richard C, Dupuy F, Behera P, Volpe F, Subramani PA, Marcel-Zerrougui B, Vallin P, Andrieu M, Minz AM, Azar N, Martins RM, Lorthiois A, Gazeau F, Lopez-Rubio JJ, Mazier D, Silva AKA, Satpathi S, Wassmer SC, Verdier F, Lavazec C. Plasmodium falciparum sexual parasites develop in human erythroblasts and affect erythropoiesis. Blood. 2020 Sep 17;136(12):1381-1393 

3. Das S, Boeykens L, Loubens M, Marinach C, Briquet S, De Vocht L, Pintelon I, Timmermans JP, Sterckx YGJ, Silvie O. A structure-based epitope tagging approach identifies vulnerable sites on the malarial P36-P52 protein complex for antibody-mediated neutralization of Plasmodium sporozoites. Plos Pathogens in press

4. Loubens M, Marinach C, Paquereau CE, Hamada S, Hoareau-Coudert B, Akbar D, Franetich JF, Silvie O. The claudin-like apicomplexan microneme protein is required for gliding motility and infectivity of Plasmodium sporozoites. PLoS Pathog. 2023 Mar 16;19(3):e1011261. doi: 10.1371/journal.ppat.1011261

5. Fernandes P, Loubens M, Le Borgne R, Marinach C, Ardin B, Briquet S, Vincensini L, Hamada S, Hoareau-Coudert B, Verbavatz JM, Weiner A, Silvie O. The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts. PLoS Pathog. 2022 Jun 22;18(6):e1010643. doi: 10.1371/journal.ppat.1010643