Investigating!the!influence!and!therapeutic!potential!of!RNA!G^quadruplex!structures!on!positive! (360G-Wellcome-105389_Z_14_Z)

£160,792

An!increasing!body!of!evidence!suggests!that!RNA!secondary!structures,!such!as!G] quadruplexes!and!stem]loops,!play!crucial!roles!in!the!regulation!of!translation!and!RNA! replication!during!viral!infection.!Our!ability!to!exploit!such!RNA!structures!therapeutically!is! dependent!upon!our!knowledge!of!how!they!act,!which!remains!unclear.!!One!goal!of!this! research!is!to!systematically!identify!and!examine!the!influence!of!RNA!G]quadruplexes! present!in!the!coding!regions!of!two!widely!used!model!calciviruses.!Using!the!established! reverse!genetic!systems!for!these!viruses,!the!effects!of!mutations!that!alter!the!presence!and! distribution!of!G]quadruplex!structures!can!be!studied,!both!in!terms!of!virus!efficiency!and!rate! of!RNA!synthesis!in!cell!culture.!If!suitable!mutated!viruses!are!obtained,!the!persistence!of! these!viruses!within!a!small!animal!model!will!be!examined!which!will!give!insights!into!the! suitability!of!such!modified!viruses!for!use!as!vaccines.!The!second!goal!of!this!research!is!to! investigate!the!mechanisms!by!which!helicases!control!the!regulation!imposed!by!such!RNA! structures.!Using!a!reconstitution!system!for!translation!initiation!in & vitro,!the!hierarchy!between! different!RNA!secondary!structures!and!the!helicases!that!mediate!their!unwinding!can!be! examined.

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Grant Details

Amount Awarded 160792
Applicant Surname Sanford
Approval Committee PhD Studentships
Award Date 2014-07-14T00:00:00+00:00
Financial Year 2013/14
Grant Programme: Title PhD Studentship (Basic)
Internal ID 105389/Z/14/Z
Lead Applicant Mr Thomas Sanford
Partnership Value 160792
Planned Dates: End Date 2018-10-01T00:00:00+00:00
Planned Dates: Start Date 2014-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Paul Lehner