Objetivo Malaria remains a major problem of public health in developing countries. It is responsible for about 600000 deaths per year, predominantly children in sub-Saharan Africa. There is an urgent need for novel therapies as resistance against current treatments is widespread. The complex parasite biology requires a multifaceted approach targeting multiple life cycle stages and virulence pathways. The pathogenesis of the most deadly of human malaria parasites, Plasmodium falciparum, is related to the capability of infected red blood cells to sequester in deep tissues. Sequestration is critical for the completion of the red blood cell cycle because the release of parasites into the blood circulation allows recognition by surveillance macrophages and clearance in the spleen. A series of studies have since led to the understanding that sequestration of asexually replicating parasites is caused by the adherence of parasite infected red blood cells to the vascular endothelium of various tissues in the body. We have recently demonstrated that gametocytes, the only stage capable of transmission to the mosquito vector, develop in the extravascular environment of the human bone marrow. Preliminary studies in the mouse model have confirmed this finding and also suggest existence of an asexual reservoir in the bone marrow. In this innovative multidiscipinary proposal we aim to investigate the host pathogen interactions at the interface between infected red blood cell and bone marrow vasculature. Specifically we will focus on the following questions: how do parasites home to bone marrow? What are the changes in the bone marrow endothelium upon infection? How do parasites adhere with and transmigrate across the vascular endothelium in the bone marrow? The proposed studies initiate detailed characterization of a new paradigm in malaria parasite interaction with the host vasculature and provide a compelling new avenue for intervention strategies. Ámbito científico medical and health scienceshealth sciencesinfectious diseasesmalariamedical and health scienceshealth sciencespublic healthmedical and health sciencesbasic medicineimmunologymedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemedical and health sciencesbasic medicinepathology Palabras clave Host pathogen interactions Malaria pathogen transmission bone marrow homing vascular adherence Programa(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Tema(s) ERC-CoG-2015 - ERC Consolidator Grant Convocatoria de propuestas ERC-2015-CoG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-COG - Consolidator Grant Institución de acogida UNIVERSITY OF GLASGOW Aportación neta de la UEn € 2 298 557,00 Dirección UNIVERSITY AVENUE G12 8QQ Glasgow Reino Unido Ver en el mapa Región Scotland West Central Scotland Glasgow City Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 2 298 557,00 Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo UNIVERSITY OF GLASGOW Reino Unido Aportación neta de la UEn € 2 298 557,00 Dirección UNIVERSITY AVENUE G12 8QQ Glasgow Ver en el mapa Región Scotland West Central Scotland Glasgow City Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 2 298 557,00