Multidisciplinary approaches are used to unravel the basis of the parasitic mode of life, the survival strategies of the various eukaryotic microbes, invasion of the host, as well as the factors governing transmission from and to the blood-feeding insect.
Director: Kenneth VERNICK
Research on the malaria parasite aims at dissecting parasite invasion into host cells, erythrocyte membrane remodeling, proteolytic maturation of parasite surface antigens and antigenic variation. Other research topics include cell wall biosynthesis in A. fumigatus, biogenesis of the flagellum in T. brucei, signaling developmental programs in Leishmania parasites. Novel models have been established in order to explore host entry and dissemination of Plasmodium, Leishmania or Aspergillus. High content live imaging is used to study the dynamic cellular interactions of the Plasmodium parasites with their host during invasion and establishment in the liver, the development of Leishmania amastigotes within host cells in vitro as well as in the skin and in the liver.
Genetic mapping studies of wild Anopheles mosquitoes in Africa are used to identify the chromosomal loci that control mosquito infection by the parasites. Genomics, cell biology and biochemistry are used to understand the mechanisms that make mosquitoes susceptible or resistant to malaria parasite infection. Malaria-resistant mosquitoes are frequent in nature, and one control strategy could involve promoting the spread of naturally resistant mosquitoes in the natural population.
Malaria physiopathology is explored in vivo in a rodent model and using in vitro models for rosetting or cytoadhesion to chondroitin sulfate A. In rodents, intravital imaging is used to better define the nature of the pre-erythrocytic phase of infection. Mechanisms of parasite clearance are dissected using the unique ex vivo perfused human spleen experimental model as well as in a humanized mouse model. These studies are combined with sero-epidemiological studies in various endemic settings.
Malaria vaccine development has been a very active field with several vaccine candidates belonging to pre-erythrocytic and erythrocytic stages undergoing several phase Ia and phase Ib clinical trials in adults and in children in the field, as well as phase I and phase IIb efficacy trials in European volunteers and in African populations. Other candidates have terminated their preclinical development and are entering the clinical phases.
Since new drugs against Plasmodium, Leishmania and Aspergillus are very much needed, drug discovery is being performed by developing drug screening methodologies and identifying novel promising targets for new drugs. In the field of malaria, a therapeutic human recombinant antibody is now entering the clinical phase of development.
Lieu : A l'institut pasteur
21st Meeting of the French Society of Toxinology (SFET)
Lieu : A l'institut pasteur
4th pDC Workshop
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