Obiettivo Background: One of the major challenges for malaria control and elimination is the phenomenally efficient spread of malaria through sexual stage malaria parasites (gametocytes). The epidemiology and dynamics of gametocytes are poorly understood: it is presently unknown when commitment to gametocytes first occurs during infections and what intrinsic or extrinsic factors influence gametocyte production and infectivity to mosquitoes. I hypothesize that continuous early commitment to gametocyte production and the preferential sequestration of mature gametocytes in the subdermal vasculature are key to explaining the high efficiency of malaria transmission. Aim: This proposal has three main aims: i) to determine when commitment to gametocyte production first occurs during experimental and natural infections; ii) to delineate environmental triggers that stimulate gametocyte production in the absence and presence of treatment; iii) to quantify the differential distribution of parasite developmental stages in different compartments of the human bloodstream.Approach: We will use novel parasite stage composition assays in combination with epidemiological methods to determine the dynamics of gametocyte commitment and maturation during controlled malaria infections in malaria-naive volunteers and during naturally acquired malaria infections in cohorts exposed to malaria in Burkina Faso. A stage-specific immunohistochemistry assay will, for the first time, directly quantify malaria stage composition in the subdermal vasculature and mosquito bloodmeals and allow comparison with other compartments of the circulation. Importance and Innovation: This is the first study to comprehensively characterize gametocyte commitment, maturation and infectivity in experimental and natural infections. This proposal will provide insight in one of the most important questions for malaria elimination: what processes are responsible for the phenomenally efficient transmission of malaria. Campo scientifico scienze mediche e della salutescienze della salutemalattie infettivemalariascienze mediche e della salutescienze della salutemedicina tropicalescienze mediche e della salutescienze della salutesalute pubblicaepidemiologiascienze naturaliscienze biologichezoologiazoologia degli invertebrati Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-StG-2014 - ERC Starting Grant Invito a presentare proposte ERC-2014-STG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-STG - Starting Grant Coordinatore STICHTING RADBOUD UNIVERSITEIT Contribution nette de l'UE € 1 345 000,00 Indirizzo Houtlaan 4 6525 XZ Nijmegen Paesi Bassi Mostra sulla mappa Regione Oost-Nederland Gelderland Arnhem/Nijmegen Tipo di attività Higher or Secondary Education Establishments 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 Altri finanziamenti € 0,00 Beneficiari (3) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto STICHTING RADBOUD UNIVERSITEIT Paesi Bassi Contribution nette de l'UE € 1 345 000,00 Indirizzo Houtlaan 4 6525 XZ Nijmegen Mostra sulla mappa Regione Oost-Nederland Gelderland Arnhem/Nijmegen Tipo di attività Higher or Secondary Education Establishments 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 Altri finanziamenti € 0,00 HARVARD GLOBAL RESEARCH AND SUPPORT SERVICES INC. Partecipazione conclusa Stati Uniti Contribution nette de l'UE € 0,00 Indirizzo Office of the general counsel, holyoke center, suite 980, massachusetts avenue 1350 02138 Cambridge Mostra sulla mappa Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Altri finanziamenti € 0,00 UNIVERSITY OF GLASGOW Regno Unito Contribution nette de l'UE € 155 000,00 Indirizzo University avenue G12 8QQ Glasgow Mostra sulla mappa Regione Scotland West Central Scotland Glasgow City Tipo di attività Higher or Secondary Education Establishments 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 Altri finanziamenti € 0,00
