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Viral docking and maturation in whole bacterial cells at near atomic resolution and in 4 dimensions

Reference	BBS/E/J/000CA431
Principal Investigator / Supervisor	Professor Martin Howard
Co-Investigators / Co-Supervisors
Institution	John Innes Centre
Department	John Innes Centre Department
Funding type	Research
Value (£)	202,972
Status	Completed
Type	Institute Project
Start date	01/09/2010
End date	31/05/2014
Duration	45 months

Abstract

Host-pathogen relationships are complex, dynamic and still poorly understood. No high-resolution structural information of intact host cells infected by a pathogen has been generated in four dimensions (4D) and our quantitative understanding of the underlying molecular interactions is limited. Here, we will use Caulobacter crescentus cells infected with a virus (bacteriophage fCb13) as a simple model system to investigate the structural, genetic and kinetic basis of host-pathogen relationships in 4D by electron cryo-tomography (ECT), fluorescence microscopy (FM), genetics and mathematical modeling. The many conceptual similarities in the organization and function of prokaryotic and eukaryotic cells, lead us to hypothesize that bacteriophages, akin to eukaryotic viruses, interact with their host i) through >1 one host surface docking site (“receptor/co-receptor”), ii) at a discrete positions at the cell surface, iii) at a precise time point in the cell cycle and iv) through internal cytoskeletal structures to produce progeny. Our three-member team has targeted C. crescentus and its phage fCb13 as a host-pathogen model system. Relying on our three areas of expertise - Caulobacter genetics and fluorescence microscopy (Viollier), whole cell ECT and image processing (Wright), and mathematical modeling (Howard) – we will dissect in vitro and in situ 1) the multi-factorial nature of fCb13 infection (adsorption/adhesion/genome injection) in WT and mutants, 2) the influence of the bacterial cell-cycle and cytoskeleton on fCb13 progeny production. These cytological, genetic and quantitative studies will not only shed light on the details of fCb13 infection and progeny production specific to C. crescentus and related host-pathogen systems, but also provide conceptual insights into conserved biological principles like attachment, spatio-temporal organization and energetic coupling of (sub)cellular processes.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Microbiology, Structural Biology
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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