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Biophysical and structural investigations of DNA repair modulation by viruses. (360G-Wellcome-099765_Z_12_Z)

Viral proteins subvert various cellular processes to optimise the propogation or stable sojourn of virus genomes. Viral stealth and replication strategies can be compromised by uracil-DNA glycosylase (UDG) activity, making UDG a kown target of viruses infecting both prokaryotes and eukaryotes. In viruses of prokaryotes, UDG is silenced by the diverse protein inhibitors: a deeper investigation of structural diversity in this realm would benefit methodology in low homology bioinformatics, our understanding of protein evaluation, and inform the development of novel inhibitors of DNA repair enzymes. In human HIV-1 infections, UDG is targeted to the proteosome by association with the viral accessory protein Vpr. As a strategy for dealing with incoming virus genomes, it is possible that the UDG's ancillary role in somatic hyper-mutation may be reprised in combination with the anti-viral deoxycytidine deaminase, APOBEC3g (A3G). The HIV-1 accessory proteins Vif (targeting A3G), and Vpr, are therefore appealing anti-viral targets, and therapeutic molecules could likely be developed through biophysical and structural knowledge to their respective interactions. We aim to develop systems to identify novel viral predictors of UDG and to produce viral proteins using Vpr [and Vif with relevance to A3G] stably for biophysical and structural analyses via NMR and x-ray crystallography.


25 Jun 2012

Grant details
Amount Awarded 162047
Applicant Surname Earl
Approval Committee PhD Studentships
Award Date 2012-06-25T00:00:00+00:00
Financial Year 2011/12
Grant Programme: Title PhD Studentship (Basic)
Internal ID 099765/Z/12/Z
Lead Applicant Mr Christopher Earl
Planned Dates: End Date 2016-09-30T00:00:00+00:00
Planned Dates: Start Date 2012-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Gabriel Waksman
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