Decoding the influenza A virus polymerase-promoter complex (360G-Wellcome-098721_Z_12_Z)

£250,000

RNA viruses are masters at encoding an extraordinary number of functions in a relatively limited amount of genomic space. To achieve this, they densely integrate functions or employ functional components for multiple purposes. An elegant example is the RNA promoter that flanks all genes encoded by influenza A virus, an RNA virus that is a significant threat to our health and economy. Although the minimal promoter structure consists of only a total of 25 partially duplexed RNA nucleotides, it is specifically bound by the influenza polymerase and able to direct the replication, transcription, and packaging of all influenza genome segments through a poorly understood mechanism. In this proposal, I aim to fully uncover the mechanistic details behind the multi-functionality of this RNA structure and the interplay among the components of the promoter-polymerase complex. To this end, I propose a multidisciplinary approach, which includes an in vitro single-molecule study and an in vivo single -molecule method to acquire high-resolution activity data of the polymerase on wild-type and mutant promoters. New insights obtained with these techniques will reveal specific kinetic steps that could help us explain the mechanism of influenza A RNA synthesis and that could provide a target for anti-influenza drug development.

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Grant Details

Amount Awarded 250000
Applicant Surname te Velthuis
Approval Committee Sir Henry Wellcome Postdoctoral Fellowships Interview Committee
Award Date 2012-05-28T00:00:00+00:00
Financial Year 2011/12
Grant Programme: Title Sir Henry Wellcome Postdoctoral Fellowship
Internal ID 098721/Z/12/Z
Lead Applicant Dr AJ te Velthuis
Partnership Value 250000
Planned Dates: End Date 2017-04-30T00:00:00+00:00
Planned Dates: Start Date 2013-05-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East
Sponsor(s) Prof Herman Waldmann