Postdoc in P. falciparum Artemisinins Resistance : Paris, France
Clearance and pitting of Plasmodium falciparum infected-RBC exposed to artemisinin as a new resistance marker
INSERM U1134, "Integrated Biology of the Red Cell" www.u1134.inserm.fr
Topic outline: The rapid clearance of parasitized RBC in patients treated with Artemisinis (the reference treatment of malaria) is in good part explained by a peculiar multistep process called "pitting" whereby parasites killed by the drug are expelled from their host RBC by the spleen. Antimalarial resistance is a major threat for Malaria eradication. Molecular markers (Pfk13 mutations), associated with parasite resistance to artemisinin in South-East Asia (defined as slow parasite clearance), may or may not be relevant markers in Africa, hence the need for a robust phenotypic test for an efficient surveillance.
Using ex vivo perfusion of human spleen and experimental systems that mimic filtration of red blood cell (RBC) by the human spleen we want to:
- discriminate and quantify the quiescent subpopulation in artemisinin-resistant strains/clones of P. falciparum
- assess whether quiescent parasites are indeed responsible for the slow parasite clearance phenotype
If successful, this approach will
- provide a new ex-vivo test to monitor the emergence of artemisinin resistance in endemic areas, that will be rapid and robust enough for a wide, standardized deployment
- open the way to screening for new pharmacological agents specifically active on quiescent parasites
- A recent Ph.D. in microbiology and/or cell & molecular biology
- Expertise in cell-cell interactions and protein fonctions and specially on red cell and or Plasmodium falciparum
- Experience in working in the context of collaborative networks with multiple partners
- Good communication skills
Start date : Q1 2018
Duration : 24 months funded with potential prolongation depending on ongoing grant application.
Deadline : Sooner is better. Position will remain open until filled.
Main references of the team in the field :
Ndour PA, Larréché S., Mouri O., Argy N., Gay F., Roussel C., Jauréguiberry S., Perillaud C., Langui D., Biligui S., Chartrel N., Kendjo E., Merens A., Ghose A., Hassan MU., Hossain MA., Kingston H., Plewes K., Danis M., Dondorp A., Hoze S., Bonnefoy S., Thellier M., Woodrow C., Buffet P¤. Measuring the Plasmodium falciparum HRP2 protein in blood from artesunate-treated malaria patients predicts post-artesunate delayed hemolysis. Science Translational. Medicine 2017. ¤ Corresponding author
Pivkin IV, Peng Z, Karniadakis GE, Buffet PA, Dao M, Suresh S. 2016. Biomechanics of red blood cells in human spleen and consequences for physiology and disease.Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7804-9.
Ndour PA, Lopera-Mesa TM, Diakité SAS, Chiang S, Mouri O, Roussel C, Jauréguiberry S, Biligui S, Kendjo E, Claessens A, Ciceron L, Mazier D, Thellier M, Diakité M, Fairhurst RM, Buffet PA. 2015. Plasmodium falciparum clearance is rapid and pitting independent in immune Malian children treated with artesunate for malaria. J Infect Dis 211:290-297.
Jauréguiberry S, Ndour PA, Roussel C, Ader F, Safeukui I, Nguyen M, Biligui S, Ciceron L, Mouri O, Kendjo E, Bricaire F, Vray M, Angoulvant A, Mayaux J, Haldar K, Mazier D, Danis M, Caumes E, Thellier M, Buffet P, French Artesunate Working Group. 2014. Postartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins. Blood 124:167-175.
Duez J, Holleran JP, Ndour PA, Loganathan S, Amireault P, Français O, Nemer W El, Le Pioufle B, Amado IF, Garcia S, Chartrel N, Le Van Kim C, Lavazec C, Avery VM, Buffet PA. 2015. Splenic retention of Plasmodium falciparum gametocytes to block the transmission of malaria. Antimicrob Agents Chemother 59:4206-14.
Deplaine G, Safeukui I, Jeddi F, Lacoste F, Brousse V, Perrot S, Biligui S, Guillotte M, Guitton C, Dokmak S, Aussilhou B, Sauvanet A, Cazals Hatem D, Paye F, Thellier M, Mazier D, Milon G, Mohandas N, Mercereau-Puijalon O, David PH, Buffet PA. 2011. The sensing of poorly deformable red blood cells by the human spleen can be mimicked in vitro. Blood 117:e88-95.
Buffet PA, Safeukui I, Deplaine G, Brousse V, Prendki V, Thellier M, Turner GD, Mercereau-Puijalon O. 2011. The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiology. Blood 117:381-392.
Buffet PA, Milon G, Brousse V, Correas J-M, Dousset B, Couvelard A, Kianmanesh R, Farges O, Sauvanet A, Paye F, Ungeheuer M-N, Ottone C, Khun H, Fiette L, Guigon G, Huerre M, Mercereau-Puijalon O, David PH. 2006. Ex vivo perfusion of human spleens maintains clearing and processing functions. Blood 107:3745-3752.
Please email to Alioune Ndour and to Pierre Buffet :
1) a cover letter detailing motivation, research interests, a concise summary of previous research activities and your curriculum vitae,
2) Two letters of recommendation to be sent directly.
sous la référence "www.123bio.eu/PostDoc"
Team 4 " Tissular Biology of the Red Cell ",