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  Using genome sequence data to combat antimicrobial resistance


   College of Medicine and Veterinary Medicine

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  Prof M Woolhouse, Prof R Fitzgerald  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

Whole genome sequencing (WGS) is now routinely applied to characterize pathogenic bacteria in multiple ways, including their antimicrobial resistance (AMR) profiles. However, the sample- to-actionable genome (StAG) pipeline is still too slow to be clinically relevant. This project will tackle a key element of StAG by developing a suite of bioinformatics algorithms that convert raw sequence data to comprehensive typing information on pathogenic bacteria in a faecal, blood or respiratory sample. To be clinically useful (i.e. fast) and to supersede traditional laboratory culturing of bacteria, we need to be able to use culture-free data obtained by ‘agnostic’ direct sequencing of samples. This represents an intriguing and challenging bioinformatics problem which is the key element of this project.

WGS data can also be used to track the movement of bacteria and/or resistance determinants between different populations, here between humans and livestock populations in Kenya. This is important because the extent to which antibiotic usage in livestock contributes to the burden of resistance in human populations has yet to be quantified in this setting, and will have practical implications in terms of regulating antibiotic usage.

Microbiological validation will take place at a laboratory in Nairobi. Bacteria will be typed for pathotype and virulence factors, as well as AMR profiles, particularly to drugs used in Kenya as first line treatments for sepsis and urinary tract infections (chloramphenicol, gentamicin, amoxicillin and cotrimoxazole). The specificity and sensitivity of sequence-based typing will be quantified.
The project is expected to result in several high impact publications in scientific journals. In addition, by linking the bioinformatics pipeline to portable, rapid sequencing platforms there is the opportunity to help develop a one-stop bacterial typing system suitable for use even in remote settings, providing vital clinical information in real time without the need to submit specimens to a central laboratory facility, a step change in diagnostic capability that will help save lives.

The project will provide the student with multiple training opportunities in microbiology, bioinformatics and diagnostics. The student will gain experience of field work overseas (in Kenya) and, importantly, of integrating field and laboratory studies – involving both bacterial typing and genome sequencing – with state-of-the-art quantitative analysis, especially bioinformatics but also elements of statistical epidemiology and phylogeographic analyses. Formal training in bioinformatics will be provided during Year 1 and support for the student will be available throughout. The student will be part of a large group of researchers working on related problems that will provide a stimulating, supportive and world class academic environment.

Application
This MRC DTP programme is joint between the Universities of Edinburgh and Glasgow. You will be registered at the host institution of the primary supervisor detailed in your project selection.

You can apply here via the University of Glasgow: http://www.gla.ac.uk/research/opportunities/howtoapplyforaresearchdegree/
Within the application, at the programme of study search field option, please select ‘MRC DTP in Precision Medicine’.

Please note that, in step 6 within the online application process, you are asked to detail supervisor/project title information. Please ensure that you clearly detail this information from the information provided within this abstract advert. Within the research area text box area, you can also add further details if necessary.

Please ensure that all of the following supporting documents are uploaded at point of application:
• CV/Resume
• Degree certificate (if you have graduated prior to 1 July 2016)
• Language test (if relevant)
• Passport
• Personal statement
• Reference 1 (should be from an academic who has a knowledge of your academic ability from your most recent study/programme)
• Reference 2 (should be from an academic who has a knowledge of your academic ability)
• Transcript

For more information about Precision Medicine at the University of Edinburgh, visit http://www.ed.ac.uk/medicine-vet-medicine/postgraduate/research-degrees/phds/precision-medicine

Funding Notes

Start date:
September/October 2016

Qualifications criteria:
Applicants applying for a MRC DTP in Precision Medicine studentship must have obtained, or soon will obtain, a first or upper-second class UK honours degree or equivalent non-UK qualifications, in an appropriate science/technology area.

Residence criteria:
The MRC DTP in Precision Medicine grant provides tuition fees and stipend of £14,296 (RCUK rate 2016/17) for UK and *EU nationals that meet all required eligibility criteria.

(*must have been resident in the UK for three years prior to commencing studentship)

Full qualifications and residence eligibility details are available here: http://www.mrc.ac.uk/skills-careers/studentships/studentship-guidance/student-eligibility-requirements/

General enquiries regarding programme/application procedure: [Email Address Removed]

References

1. Woolhouse, M., Ward, M., van Bunnik, B. and Farrar, J. (2015). Antimicrobial resistance in humans, livestock and the wider environment. Philosophical Transactions of the Royal Society, Biological Sciences 370: e20140083 (7pp).
2. McAdam, P.R., Richardson, E.J. and Fitzgerald, J.R. (2014). High-throughput sequencing for the study of bacterial pathogen biology. Current Opinion in Microbiology 19: 106-113.
3. Ward, M.J., Gibbons, C.L., McAdam, P.R., van Bunnik, B.A.D., Girvan, E.K., Edwards, G.F. Fitzgerald, J.R. and Woolhouse, M.E.J. (2014). Time-scaled evolutionary analysis of the transmission and antibiotic resistance dynamics of Staphylococcus aureus CC398. Applied and Environmental Microbiology 80: 7275-7282.

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