Objective 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. Fields of science 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) Topic(s) ERC-SG-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Call for proposal ERC-2013-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM EU contribution € 1 499 942,00 Address DR MOLEWATERPLEIN 40 3015 GD Rotterdam Netherlands See on map Region West-Nederland Zuid-Holland Groot-Rijnmond Activity type Higher or Secondary Education Establishments Administrative Contact Riet Van Zeijl (Mrs.) Principal investigator Tokameh Mahmoudi (Dr.) 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 ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM Netherlands EU contribution € 1 499 942,00 Address DR MOLEWATERPLEIN 40 3015 GD Rotterdam See on map Region West-Nederland Zuid-Holland Groot-Rijnmond Activity type Higher or Secondary Education Establishments Administrative Contact Riet Van Zeijl (Mrs.) Principal investigator Tokameh Mahmoudi (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data