Objective Inhibiting transmission of the malaria parasite from infected humans to the mosquito vector would be of considerable interest in the context of malaria control, especially in order to prevent the dissemination of drug-resistant genotypes. Since only sexual forms of the parasite (the gametocytes) are infective to the mosquito, blocking gametocytogenesis would prevent transmission. The molecular control of gametocytogenesis is not understood. Our laboratories have independently brought significant contributions to the characterisation of (i) components of signalling pathways, some of which are likely to be involved in differentiation, and (ii) proteins expressed at the onset of gametocytogenesis, such as Pfg27 and Pfs16. We propose to merge these lines of investigation to generate an integrated picture of the early events of sexual development at the molecular level. Furthermore, we will develop screening assays for enzymes suspected to be involved in gametocytogenesis, to identify compounds able to interfere with malaria transmission. Specific objectives of the network are: -to establish a map of protein-protein interactions for molecules expressed at the onset of gametocytogenesis, identified within the network by conventional and genome-wide approaches; -to define the role of phosphorylation of Pfg27, an RNA-binding phosphoprotein essential to sexual development whose structure is solved, integrating biochemical, functional and structural approaches; -to establish the role that protein kinases and proteins expressed specifically in early gametocytes play in differentiation, using a reverse genetics approach; -to elucidate the organization of signalling pathways thought to be involved in gametocytogenesis, such as the cyclic nucleotide and MAPK pathways, central components of which have been characterised in our laboratories. -to establish biochemical assays for signalling protein kinases, and optimize such assays to medium throughput screening. Fields of science medical and health scienceshealth sciencesinfectious diseasesmalarianatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencesgeneticsnucleotidesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymesnatural sciencesbiological scienceszoologyinvertebrate zoology Keywords Malaria antimalarial gametocytogenesis signal transduction Programme(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Topic(s) LIFESCIHEALTH-2.3.0 - Developing new promising candidate vaccines and therapies Call for proposal FP6-2003-LIFESCIHEALTH-3 See other projects for this call Funding Scheme STREP - Specific Targeted Research Project Coordinator INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE Address 101, rue de tolbiac Paris France See on map Links Website Opens in new window EU contribution No data Participants (5) Sort alphabetically Sort by EU Contribution Expand all Collapse all LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE United Kingdom EU contribution € 0,00 Address Keppel street London See on map Links Website Opens in new window Other funding No data INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY India EU contribution € 0,00 Address Aruna asaf ali road New delhi See on map Links Website Opens in new window Other funding No data CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE France EU contribution € 0,00 Address 3 rue michel-ange Paris See on map Links Website Opens in new window Other funding No data UNIVERSITY OF NAIROBI Kenya EU contribution € 0,00 Address Riverside drive, chiromo campus Nairobi See on map Links Website Opens in new window Other funding No data ISTITUTO SUPERIORE DI SANITÀ Italy EU contribution € 0,00 Address Viale regina elena n. 299 Rome See on map Links Website Opens in new window Other funding No data
