Award details

Rapid bacterial Virulence Annotation for the post genomic era

ReferenceBB/E021182/1
Principal Investigator / Supervisor Professor Richard Ffrench-Constant
Co-Investigators /
Co-Supervisors
Institution University of Exeter
DepartmentBiosciences
Funding typeResearch
Value (£) 378,038
StatusCompleted
TypeResearch Grant
Start date 05/11/2007
End date 04/08/2011
Duration45 months

Abstract

This project plans to bridge the gap between bacterial genome sequences and their functional annotation. We have set up a number of parallel screens against different organisms that allow for the rapid identification of putative virulence factors from end-sequenced cosmid libraries. Briefly, we will prepare cosmid libraries from three important pathogenic bacteria; Yersinia pseudotuberculosis strain IP32953, Francisella tularensis subspecies tularensis strain SCHU S4 and Campylobacter jejuni strain 81-176 and end-sequence these entire libraries. We will then ordinate these end sequences onto the published genomes to validate the quality and coverage of the libraries. The cosmid screens rely on the recovery of individual comids (when screened individually, for example via insect injection) or groups of cosmids (when screened as pools of clones or whole libraries) that map together in different screens. Preliminary data from the emerging human pathogen Photorhabdus asymbiotica shows that cosmids cluster in different screens depending on the apparent mode of action of the different virulence factors they contain. For example, cell toxicity or the promotion of intracellular survival. We will analyse candidates from these clusters of cosmids via transposon mutatagenesis in order to identifiy the genes responsible and post this functional annotation on a web site. This will allow other workers in the field to access the data and request specific cosmids. Alternatively, we will enter into specific collaborations to further test a range of cosmids and their associated transposon mutants with groups interested in a specific virulence factor. In this manner we will develop a community based resource designed to reduce the use of costly animal testing and to promote the functional annotation of novel virulence factors in bacterial genomes.

Summary

see Bath proposal
Committee Closed Committee - Genes & Developmental Biology (GDB)
Research TopicsAnimal Health, Microbial Food Safety, Microbiology, The 3 Rs (Replacement, Reduction and Refinement of animals in research)
Research PriorityX – Research Priority information not available
Research Initiative X - not in an Initiative
Funding SchemeX – not Funded via a specific Funding Scheme
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