Objective As the major target for therapy, Reverse Transcriptase (RT), and in particular the RT from the HIV virus, has been the subject of extensive research. However, despite an ever-increasing amount of information from traditional “bulk” studies, the detailed mechanisms of polymerization are still not completely understood. This is due, partially, to the stochastic nature of individual enzymes, which makes it impossible to follow more than one or two individual steps of polymerization using ensemble methods. I propose here to conduct a single-molecule, mechanistic study of HIV RT, by developing a high-resolution optical-tweezers, capable of resolving the individual polymerization and translocation steps of RT at a broad range of forces and nucleotides concentrations. Characterizing the dwell-time distribution at different experimental condition will allow us to study the complete mechano-chemical cycle of RT, its regulation by the template’s backbone-composition, structure and sequence, its interaction with additional viral and host factors, the molecular basis of inhibition by known inhibitors and the mechanism of resistance acquired through different mutations. Fields of science natural sciencesbiological sciencesmicrobiologyvirologymedical and health scienceshealth sciencesinfectious diseasesRNA virusesHIVnatural sciencesbiological sciencesgeneticsnucleotidesnatural sciencesbiological sciencesbiophysicsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2011-CIG - Marie-Curie Action: "Career Integration Grants" Call for proposal FP7-PEOPLE-2011-CIG See other projects for this call Funding Scheme MC-CIG - Support for training and career development of researcher (CIG) Coordinator TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY EU contribution € 100 000,00 Address SENATE BUILDING TECHNION CITY 32000 Haifa Israel See on map Activity type Higher or Secondary Education Establishments Administrative Contact Mark Davison (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
