Characterisation of the Type Three Secretion System Effector NleG (360G-Wellcome-097009_Z_11_Z)

£156,706

Enterohaemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli, which share an infection strategy with the mouse-specific pathogen Citrobacter rodentium, colonise the human intestine is conferred by a Type III secretion system that translocates bacterial 'effector' proteins into enterocytes, wherethey subvert cellular pathways and central organelles. The focus of this project is the NleG effectors, which mimic the structure andfunction of eukaryotic RING finger/U-box ubiquitin E3 ligases. While EHEC contains 9 NleG orthologs, EPEC strain E2348/69 and C. rodentium contain one and three homologs respectively. The targets and role in virulence of the NleGs remain unknown. During Bevin's rotation we found that EHEC NleG targets the nucleus, resulting in diminished staining intensity of histone H3, while NleG7 is found diffused in the cytosol. The goals of this project are to: 1. Determine the intracellular trafficking of the NleGs 2. Identify the NleGs' substrate proteins and the role of the NleGs' in cell signalling 3. Determine the impact of the NleGs on nuclear and cytosolic proteins' ubiquitylation and turnover 4. Determine the role of NleGs during infection using in vivo models

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Grant Details

Amount Awarded 156706
Applicant Surname McGeever
Approval Committee Immunology and Infectious Disease Funding Committee
Award Date 2011-08-31T00:00:00+00:00
Financial Year 2010/11
Grant Programme: Title PhD Studentship (Basic)
Internal ID 097009/Z/11/Z
Lead Applicant Ms Bevin McGeever
Partnership Value 156706
Planned Dates: End Date 2015-08-31T00:00:00+00:00
Planned Dates: Start Date 2011-09-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Murray Selkirk