Objective
The oncogenic human immunodeficiency virus (HIV) currently infects an estimated 33 million individuals and has claimed more than 25 million lives. The primary treatment of HIV consists of a cocktail of several classes of antiretroviral drugs targeting various components of the HIV virus. The most utilized target of antiretroviral drugs is reverse transcriptase (RT), an enzyme that transforms the viral genome from ssRNA to dsDNA. Unfortunately, significant gaps remain in our understanding of how RT functions. Using single molecule techniques, I have previously shown that the orientation of RT while associated with nucleic acids is highly dynamic and characterized by both flipping and sliding transitions. These transitions are associated with processing of the poly-purine tract (PPT) sequence, the rapid targeting of RT to the ends of long regions of double stranded nucleic acids, and strand displacement synthesis. In this grant, I propose to develop additional single molecule assays to further study the dynamic interactions of RT with physiologically relevant nucleic acid substrates. These new assays will allow my lab to address specific questions relevant to the understanding of this key enzyme. First, we will determine the mechanisms of the flipping and sliding transitions and test whether these transitions are required for the successful completion of key steps in the reverse transcription reaction. Second, we will probe the detailed mechanism of strand displacement synthesis and determine the energetic contacts RT uses to stabilize the annealed primer strand. Finally, we will also measure the effects of antiretroviral drugs in preventing the completion of individual steps of the reverse transcription process to identify potentially novel mechanisms of inhibition. Taken together, this research offer fundamental insights into protein and nucleic acid interactions and help to define the next generation of anti-HIV drugs.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules nucleic acids
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences genetics genomes viral genomes
- medical and health sciences health sciences infectious diseases RNA viruses HIV
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2011-CIG
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
2628 CN DELFT
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.