Objectif The persistence of a transcriptionally competent but latent HIV infected memory CD4+T cell reservoir, despite the effectiveness of Highly Active Antiretroviral therapy (HAART) against active virus, presents the main impediment to HIV eradication. A novel concept in HIV eradication is to activate latent virus to subsequently eliminate with HAART. Much effort has gone into identification of protein complexes that regulate HIV LTR activity. Strategies have mainly relied on candidate approaches. However, due to technical limitations, comprehensive unbiased identification of host proteins associated with and necessary for silencing of the latent HIV LTR has not been possible.Trxn-PURGE proposes a novel multidisciplinary approach combining current knowledge of HIV transcription and new insights into eradication strategies with state of the art high though-put approaches, mycology, virology, genetics and conventional biochemistry to identify novel players in maintenance and activation of HIV transcriptional latency. We will: 1. Use a novel unbiased strategy to identify the in vivo latent LTR-bound protein complex directly from infected T cells. 2. Conduct a cell-based high-throughput Haploid genetic screen to identify novel factors essential for maintenance of HIV latency. 3. Having identified three putative activators from a limited library, we will perform a large-scale screen with unbiased library of fungal supernatants to identify molecules capable of activation of latent HIV.These parallel approaches will identify novel molecular targets and molecules in activation of HIV transcriptional latency, which we will functionally and mechanistically characterize alone and in synergy with known compounds implicated in latent LTR activation in both 4. T cell lines and 5. primary human CD4+T cells harboring latent HIV.By unravelling its molecular mechanisms, Trxn-PURGE will set the stage for the development of a clinical combinatorial therapy to activate latent HIV. Champ scientifique natural sciencesbiological sciencesgeneticsnatural sciencesbiological sciencesmicrobiologyvirologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesmicrobiologymycologymedical and health scienceshealth sciencesinfectious diseasesRNA virusesHIV 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) Thème(s) ERC-SG-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Appel à propositions ERC-2013-StG Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM Contribution de l’UE € 1 499 942,00 Adresse DR MOLEWATERPLEIN 40 3015 GD Rotterdam Pays-Bas Voir sur la carte Région West-Nederland Zuid-Holland Groot-Rijnmond Type d’activité Higher or Secondary Education Establishments Contact administratif Riet Van Zeijl (Mrs.) Chercheur principal Tokameh Mahmoudi (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM Pays-Bas Contribution de l’UE € 1 499 942,00 Adresse DR MOLEWATERPLEIN 40 3015 GD Rotterdam Voir sur la carte Région West-Nederland Zuid-Holland Groot-Rijnmond Type d’activité Higher or Secondary Education Establishments Contact administratif Riet Van Zeijl (Mrs.) Chercheur principal Tokameh Mahmoudi (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée