Funded PhD Opportunity Production and use of novel, deuterated antibiotics as a tool to combat resistance among pathogenic microorganisms from the gut microbiome

This opportunity is now closed.

Subject: Biomedical Sciences

Summary

The project builds on well-established and well-funded programmes of research linking ongoing activities with gut microbiomes aligned with the global challenge of combatting antimicrobial resistance by allowing for the reuse of existing antibiotics. Perhaps the biggest problem facing health services worldwide is the rapid increase in acquired antibiotic resistance in pathogenic bacteria.  The scale of this threat has recently been highlighted by the UK Chief Medical Officer, who has pointed out that the paucity of new antibiotics being introduced could lead to a catastrophic situation within a few years. We can no longer rely on traditional antibiotic discovery approaches and this problem can only be addressed by a novel approach to developing new antibiotics.

Our research strategy is to subtly alter current antibiotics so that they are not affected by resistance mechanisms but still retain antibacterial activity. During a recent research project on the role of bacterial biosurfactants in biofilm development we were able to develop a process which allowed the production of specifically labelled biosurfactant molecules with deuterium, the heavy non-radioactive isotope of hydrogen.  There are a few recent reports in the literature suggesting that drugs containing deuterium can be more effective than the conventional form as, a result of decreased rates of biodegradation in the body without any reported toxic or harmful effects.  This characteristic allows much lower doses to be used, reducing side-effects and cost.

It is clear from our own published work that the metabolism of some bacteria is disrupted by the presence of the deuterium in metabolites.  These observations have allowed us to formulate a hypothesis that microbially synthesised antibiotics could be produced containing deuterium and that such antibiotics might circumvent the acquired drug resistance in bacteria due to altered physico-chemical properties disrupting enzyme substrates recognition processes. One of the most frequently encountered mechanisms of drug resistance is biodegradation of the antibiotic in the resistant bacterial strain. This is particularly true for the ß lactam antibiotics, one of the most clinically important drug families, and also for the aminoglycosides.

Our research group has a wealth of experience of growing microorganisms that produce antibiotics and we have been studying antibiotic resistant organisms for over a decade. We have been focussing much of our efforts on bacteria that inhabit the human gut. Organisms such as the gastrointestinal bacterium E. coli expressing Extended Spectrum Beta Lactamases (ESBLs) are one of the most commonly encountered healthcare associated infections and their incidence is increasing. There is an urgent need to find alternative treatments for this organism.

The aim of this project would be to produce selectively deuterated beta lactam antibiotics (both site-directed deuteration and level of deuteration) to start with. This can be accomplished relatively easily in the laboratory scale fermenters that we have used to produce deuterated biosurfactants. Once the drugs have been chemically characterised they will be used to determine if antibiotic resistance by some ESBL producing E. coli strains is ameliorated.  Once we have established the value of the deuteration approach we can subsequently extend a successful initial outcome to develop a platform technology, which could be widely applied to the production of a range of deuterated antibiotics.

This project will be based at Ulster's Nutrition Innovation Centre for Food and Health (NICHE).

Essential Criteria

  • Upper Second Class Honours (2:1) Degree from a UK institution (or overseas award deemed equivalent via UK NARIC)
  • Sound understanding of subject area as evidenced by a comprehensive research proposal
  • A comprehensive and articulate personal statement

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

  • First Class Honours (1st) Degree
  • Completion of Masters at a level equivalent to commendation or distinction at Ulster
  • Research project completion within taught Masters degree or MRES
  • Experience using research methods or other approaches relevant to the subject domain
  • Work experience relevant to the proposed project
  • Publications - peer-reviewed
  • Experience of presentation of research findings

Funding

    Vice Chancellors Research Scholarships (VCRS)

    The scholarships will cover tuition fees and a maintenance award of £14,777 per annum for three years (subject to satisfactory academic performance). Applications are invited from UK, European Union and overseas students.

    DFE

    The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £ 14,777 per annum for three years. EU applicants will only be eligible for the fees component of the studentship (no maintenance award is provided).  For Non EU nationals the candidate must be "settled" in the UK.

Other information

The Doctoral College at Ulster University

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Key Dates

Submission Deadline
Monday 19 February 2018
Interview Date
6, 7 and 8 March 2018

Contact Supervisor

Professor James Dooley

Other Supervisors

Apply online

Visit https://www.ulster.ac.uk/applyonline and quote reference number #237679 when applying for this PhD opportunity