Objective 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. Fields of science medical and health scienceshealth sciencesinfectious diseasesmalarianatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological scienceszoologyinvertebrate zoology Programme(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) Topic(s) ERC-AG-LS6 - ERC Advanced Grant - Immunity and infection Call for proposal ERC-2009-AdG See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution INSTITUT PASTEUR EU contribution € 1 815 480,00 Address RUE DU DOCTEUR ROUX 25-28 75724 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Principal investigator Arthur Helmut Scherf (Prof.) Administrative Contact Marie-Laure Rosso (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all INSTITUT PASTEUR France EU contribution € 1 815 480,00 Address RUE DU DOCTEUR ROUX 25-28 75724 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Principal investigator Arthur Helmut Scherf (Prof.) Administrative Contact Marie-Laure Rosso (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
