Award details

Role of dynamics in the initiation of RNA bacteriophage assembly

Reference	BB/D01025X/1
Principal Investigator / Supervisor	Professor Steve Homans
Co-Investigators / Co-Supervisors	Professor Peter Stockley, Professor Nicola Jane Stonehouse, Dr Gary Thompson
Institution	University of Leeds
Department	Inst of Molecular & Cellular Biology
Funding type	Research
Value (£)	65,692
Status	Completed
Type	Research Grant
Start date	15/12/2005
End date	14/12/2006
Duration	12 months

Abstract

We seek one year funding to allow completion of a project aimed at understanding in molecular detail the assembly pathway of a simple viral capsid shell, using as a model the RNA phage MS2. Simple thermodynamic arguments show that assembly will depend not only upon the spatial disposition of the interacting species (loosely, enthalpy), but also upon changes in dynamics (entropy). Indeed, from work to date we already know that interesting dynamic processes accompany assembly. Our approach will therefore involve the NMR analysis of the RNA operator / coat protein dimer complex (TR-CP2), in an effort to delineate the role of these dynamics in complex formation. This will involve the acquisition data on CP2 both free and in complex with TR as well as well as on TR alone and will lead to a detailed comparison of global thermodynamics of binding of TR to CP2.

Summary

At their simplest, viruses are complex molecular machines capable of gaining entry into target cells, where they release their cargoes of nucleic acid molecules which can then redirect the activities of the host cell to make new copies of the virus. The attachment, disassembly and subsequent assembly of new virus particles is a complex process but largely proceeds automatically by a process known as self-assembly. This can be described as a set of Lego bricks being able to stick themselves together in order to build a house. However, the process is more complex than this, as the 'bricks' may also change shape when they contact their neighbouring subunits. It is likely that many processes in cells involve changes in the shapes of molecules and it is important to understand how these occur as this may eventually reveal new ways to interfere with undesirable events e.g. to develop new anti-viral strategies. We are proposing to study this using a simple virus system and will use techniques that allow us to observe the behaviour and shape of molecules both in isolation and early in the self-assembly process.

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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