Objetivo An important number of human and animal pathogens use antigenic variation of surface proteins as a mechanism to avoid destruction by the host s immune system. Most escape mechanisms rely on the successive expression of members of gene families in a mutually exclusive manner, a biological process which remains elusive at the molecular level. The protozoan pathogen Plasmodium falciparum, which infects up to 300 million people causing more than two million lives each year, undergoes antigenic variation to establish chronic blood stage infection. A critical determinant in chronic infection and pathogenesis is the expression of clonally variant molecules at the surface of infected erythrocytes. Several variant gene families undergo antigenic variation in P. falciparum and are expressed during blood stage infection. One family encoded by 60 var genes expresses the most well-known virulence factor causing severe malaria (capillary blockages in the brain and other organs mediated by infected erythrocytes). Switching expression between the 60-member var gene family avoids immune clearance and prolongs the period of infection and transmission to the mosquito. The initial event controlling mono allelic expression at a unique expression site remains elusive and represents the Holly Graal in the field of phenotypic variation. To this end, the major objective of this proposal is to identify specific factors contributing to active expression sites (proteins, DNA enhancer or ncRNA) by using novel strategies such as Proteomics of Isolated Chromatin segments (PICh) and Chromosome Conformation Capture (3C). We expect that new insights into the underlying principles of gene counting of virulence gene families may reveal an Achilles Heel of the parasite s immune evasion strategy. Ámbito científico medical and health scienceshealth sciencesinfectious diseasesmalarianatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological scienceszoologyinvertebrate zoology Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-AG-LS6 - ERC Advanced Grant - Immunity and infection Convocatoria de propuestas ERC-2009-AdG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-AG - ERC Advanced Grant Institución de acogida INSTITUT PASTEUR Aportación de la UE € 1 815 480,00 Dirección RUE DU DOCTEUR ROUX 25-28 75724 Paris Francia Ver en el mapa Región Ile-de-France Ile-de-France Paris Tipo de actividad Research Organisations Investigador principal Arthur Helmut Scherf (Prof.) Contacto administrativo Marie-Laure Rosso (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo INSTITUT PASTEUR Francia Aportación de la UE € 1 815 480,00 Dirección RUE DU DOCTEUR ROUX 25-28 75724 Paris Ver en el mapa Región Ile-de-France Ile-de-France Paris Tipo de actividad Research Organisations Investigador principal Arthur Helmut Scherf (Prof.) Contacto administrativo Marie-Laure Rosso (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
