Obiettivo Malaria is a devastating disease caused by the apicomplexan parasite Plasmodium. Plasmodium falciparum represents the most severe and life-threatening form of human malaria, causing over 500,000 deaths per year. There is no efficient vaccine available and resistance to all currently used drugs reported. One of the major problems in eradicating human malaria is the transmission of the parasites sexual stages, the gametocytes. These are formed in the blood and develop through five different morphological stages in specific organs of the human host. When fully mature after 10-12 days, gametocytes are released into the blood stream to be transmitted by the mosquito. The molecular regulatory mechanisms important for the formation of gametocytes are poorly understood but there is evidence showing that phosphorylation of epigenetic regulators plays a key role. The kinases that mediate these phosphorylation events and the proteins within their signalling networks, however, are not known and their identification is the aim of this proposal. Specifically I will: 1) Develop a novel tool to enrich early stage gametocytes from parasite culture using cell-type specific surface biotinylation and affinity purification. Development of this novel technology will represent a significant enhancement in our ability to study early stage gametocytes, which are currently very hard to isolate from cell culture.2) Identify the signalling pathways that are used during the early stage of sexual development by near-system-wide quantitative phosphoproteome analysis comparing early stage gametocytes from Aim 1 with asexual parasite stages.3) In a complementary approach I will systematically test 10 kinase knockout lines available in the lab for their ability to form gametocytes and gametes. The function of the kinases identified will be verified by gene complementation. Campo scientifico medical and health scienceshealth sciencesinfectious diseasesmalariamedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesnatural sciencesbiological sciencesgeneticsmutationnatural sciencesbiological sciencesgeneticsepigeneticsnatural sciencesbiological scienceszoologyinvertebrate zoology Programma(i) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Argomento(i) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Invito a presentare proposte H2020-MSCA-IF-2014 Vedi altri progetti per questo bando Meccanismo di finanziamento MSCA-IF-EF-ST - Standard EF Coordinatore THE FRANCIS CRICK INSTITUTE LIMITED Contribution nette de l'UE € 183 454,80 Indirizzo 1 MIDLAND ROAD NW1 1AT London Regno Unito Mostra sulla mappa Regione London Inner London — West Camden and City of London Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 183 454,80 Partecipanti (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto UNITED KINGDOM RESEARCH AND INNOVATION Partecipazione conclusa Regno Unito Contribution nette de l'UE € 0,00 Indirizzo POLARIS HOUSE NORTH STAR AVENUE SN2 1FL Swindon Mostra sulla mappa Regione South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Swindon Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale Nessun dato