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. Zanghì G, Vembar SS, Baumgarten S, Ding S, Guizetti J, Bryant JM, Mattei D, Jensen ATR, Rénia L, Goh YS, Sauerwein R, Hermsen CC, Franetich JF, Bordessoulles M, Silvie O, Soulard V, Scatton O, Chen P, Mecheri S, Mazier D, Scherf A. A. Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection. Cell Rep. 2018 Mar 13;22(11):2951-2963. doi: 10.1016/j.celrep.2018.02.075.

2. Manzoni G, Marinach C, Topçu S, Briquet S, Grand M, Tolle M, Gransagne M, Lescar J, Andolina C, Franetich JF, Zeisel MB, Huby T, Rubinstein E, Snounou G, Mazier D, Nosten F, Baumert TF, Silvie O. Plasmodium P36 determines host cell receptor usage during sporozoite invasion. Elife. 2017 May 16;6. pii: e25903. doi: 10.7554/eLife.25903.

3. Risco-Castillo V, Topçu S, Marinach C, Manzoni G, Bigorgne AE, Briquet S, Baudin X, Lebrun M, Dubremetz JF, Silvie O. Malaria Sporozoites Traverse Host Cells within Transient Vacuoles. Cell Host Microbe. 2015 Nov 11;18(5):593-603. doi: 10.1016/j.chom.2015.10.006.

4. Soulard V, Bosson-Vanga H, Lorthiois A, Roucher C, Franetich JF, Zanghi G, Bordessoulles M, Tefit M, Thellier M, Morosan S, Le Naour G, Capron F, Suemizu H, Snounou G, Moreno-Sabater A, Mazier D. Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice. Nat Commun. 2015 Jul 24;6:7690. doi: 10.1038/ncomms8690.

5. Dembélé L, Franetich JF, Lorthiois A, Gego A, Zeeman AM, Kocken CH, Le Grand R, Dereuddre-Bosquet N, van Gemert GJ, Sauerwein R, Vaillant JC, Hannoun L, Fuchter MJ, Diagana TT, Malmquist NA, Scherf A, Snounou G, Mazier D. Persistence and activation of malaria hypnozoites in long-term primary hepatocyte cultures. Nat Med. 2014 Mar;20(3):307-12. doi: 10.1038/nm.3461.