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Development of metabolomics for understanding AMR in mixed infections

  • Full or part time
  • Application Deadline
    Thursday, February 28, 2019
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

Without correct antibiotic stewardship we could be cast back to a pre-infective era where we have run out of antibiotics to treat life-threatening infections. Developing metabolomics-driven discovery of novel biomarkers for point-of-care delivery for assessing antimicrobial resistance (AMR) would target therapy at patient, and such companion diagnostics would allow judicious selection of antibiotic therapy.

Whilst in urinary tract infections (UTIs) many diseases are caused by a single microorganism, in the elderly poly-microbial infections often occur, and within these co-infections the different bacteria are likely to have different antibiograms. How the phenotype and biochemistry of these communities change on antimicrobial challenge may enable better antibiotic stewardship. This project will investigate Escherichia coli as these bacteria are most commonly associated with UTI, and we have a range of well characterised bacteria. The metabolic phenotyping induced upon antibiotic challenge will be analysed using a range of MS-based metabolomics including GC-MS and LC-MS and multivariate data analysis used to correlate key metabolic shifts with biochemical and pathway perturbations.

Supervisor
Roy Goodacre – https://www.liverpool.ac.uk/integrative-biology/staff/roy-goodacre/

The student will receive broad training in bioanalysis within the post-genomics sciences / systems biology interface. Specific training will be given in mass spectrometry-based metabolomics as well as multivariate data analysis.

The student will join a dynamic research group based in the IIB where the focus is to investigate cellular metabolism. Details of the current projects and diversity of work, as well as more general papers, can be found here: http://www.biospec.net/

Funding Notes

The project is open to both European/UK and International students

Funding is for four years and includes a stipend of £14,777, along with research costs of £5,000 per year.

References

AlRabiah, H., Allwood, J.W., Correa, E., Xu, Y. & Goodacre, R. (2018) pH plays a role in the mode of action of trimethoprim on E. coli. PLoS ONE 13: e0200272

Allwood, J.W., AlRabiah, H., Correa, E., Vaughan, A., Xu, Y., Upton, M. & Goodacre, R. (2015) A workflow for bacterial metabolic fingerprinting and lipid profiling: application to Ciprofloxacin challenged E. coli. Metabolomics 11, 438-453.

AlRabiah, H., Xu, Y., Rattray, N.J., Vaughan, A.A., Gibreel, T., Sayqal, A., Upton, M., Allwood, J.W. & Goodacre, R. (2014) Multiple metabolomics of uropathogenic E. coli reveal different information content in terms of metabolic potential compared to virulence factors. Analyst 139, 4193-4199.

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