Control of type III-mediated virulence by a key bacterial signal (MALONE_J17DTP)

University of East Anglia - School of Biological Sciences

Start Date:  1st October 2017

No. of positions available: 1

Supervisor: Dr Jacob Malone

Project description: 
The bacterial Type III Injectisome T3I is a needle-like structure that delivers effectors and toxins directly into host cells. The T3I plays a crucial role in pathogenicity and host infection in many bacteria, including the major human and plant pathogens P. aeruginosa and P. syringae. We recently showed that a crucial component of the T3I; the export ATPase complex, binds specifically to the signalling molecule cyclic-di-GMP (cdG), a key regulator of bacterial behaviour associated with virulence control in many bacterial pathogens.

Defining the relationship between the T3I and cdG is key to understanding T3I regulation during bacterial infections.

In this project, we will use a combination of genetics, biochemistry and structural biology to define how cdG-binding controls the T3Is of P. aeruginosa and P. syringae. The student will construct specific cdG-binding mutants in both species, and characterise them for virulence and effector protein export. These experiments will be supported by in-depth biochemical analysis of purified ATPase proteins. The emerging model for cdG-ATPase control will be refined by structural characterisation by cryo-EM and X-ray crystallography.

The student will be hosted at the world-renowned John Innes Centre, which will provide cutting-edge research facilities and a stimulating research and training environment. They will be part of an interdisciplinary, collaborative research team and will gain an excellent training in molecular microbiology, bacterial genetic manipulation, and plant infection assays, as well as advanced biochemical and structural biology techniques. The combination of transferrable, technical skills associated with the project will make the successful candidate highly employable, in industry or academia.

Person specification:  Minimum entry 2:1

Funding notes: Full Studentships cover a stipend (RCUK rate: £14,296pa – 2016/7), research costs and tuition fees at UK/EU rate, and are available to UK and EU students who meet the UK residency requirements.

Students from EU countries who do not meet the UK residency requirements may be eligible for a fees-only award. Students in receipt of a fees-only award will be eligible for a maintenance stipend awarded by the NRPDTP Bioscience Doctoral Scholarships, which when combined will equal a full studentship. To be eligible students must meet the EU residency requirements.

Details on eligibility for funding on the BBSRC website:

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