Dr D Mavridou, Prof A Filloux
No more applications being accepted
Funded PhD Project (UK Students Only)
About the Project
Disulfide bonds are ubiquitous covalent linkages, essential for the stability of hundreds of proteins. Despite their simplicity, they are formed by dedicated protein systems in all organisms. In Gram-negative bacteria, the formation of these bonds is catalysed by the Disulfide bond (DSB) formation system which is also responsible for folding most factors that enable bacteria to be efficient pathogens. More importantly, the DSB systems of pathogens are divergent compared to non-pathogenic bacteria as they contain multiple copies of key DSB players. We propose that this understudied adaptation of the DSB system allows bacteria to efficiently handle protein substrates related to pathogenesis.
Pseudomonas aeruginosa is an opportunistic pathogen which is resistant to most available antibiotics, causing financial stress to healthcare systems worldwide. Preliminary analysis of Pseudomonas species clearly revealed divergent DSB systems. We will assess the role of these proteins for Pseudomonas virulence and evaluate whether they are promising targets for the development of novel antibiotics. We are proposing the use of bioinformatics analysis for the characterisation of DSB proteins in all Pseudomonas species in combination with experimental identification of the substrates of each additional atypical DSB analogue in Pseudomonas aeruginosa to establish the involvement of the DSB system in the pathogenesis of this organism.
Dr Mavridou’s expertise in disulfide bond formation and periplasmic protein biochemistry will be complemented by Prof. Filloux’s knowledge of the lifestyle and adaptation of Pseudomonads in physiological host and non-host environments. In addition to standard biochemical and microbiological techniques, the project will require specialised biochemical assays for the identification of the substrates and the role of the DSB system in Pseudomonas aeruginosa (Mavridou lab) as well as assessment of the contribution of the DSB proteins in Pseudomonas virulence through phenotypic assays on biofilm formation, type VI secretion and virulence in the Galleria mellonella model (Filloux lab).This breadth of techniques will allow for an interdisciplinary approach where basic protein biochemistry and structure-to-function-studies will be used in the development of potential organism-specific antibacterial strategies.
Informal enquiries are welcomed and should be addressed to Dr Despoina Mavridou, [Email Address Removed]
How to apply:
Please email Dr Despoina Mavridou, [Email Address Removed], and include in your application:
A cover letter
Your CV
Your transcript (available to-date)
At least two academic references must be send directly to Dr Mavridou from the referees
Full applications made before 28th February 2017 will be considered at any time.
Funding and eligibility
The studentship covers: (i) an annual tax-free stipend at the standard Research Council rate, (ii) contribution towards research costs, and (iii) tuition fees at the UK/EU rate. Imperial College normally requires applicants for 3-year PhD positions to already have a Masters degree, at Merit level or above, by the start of the project. The BSc degree must be at 2:1 level or better in a relevant biosciences subject. Exceptional candidates without a Masters degree might be considered.
Studentships funded by UK Research Councils generally apply only to UK students or EU students who have been in the UK for at least 3 years prior to the start of the PhD.
http://www.bbsrc.ac.uk/web/FILES/Guidelines/studentship_eligibility.pdf
Overseas candidates are not eligible for this studentship.
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