PhD Study : Harnessing the communication machinery of antibiotic resistant, gastrointestinal bacteria to develop novel pathogen detection strategies

Apply and key information  

Summary

Background to the project

Bacteria with resistance against multiple antibiotics have become a frequent complication in health care, often endangering successful outcomes of routine medical interventions. Enterococci were considered harmless bacterial members of the gastrointestinal microbiome.  However, multi-drug resistant enterococcal infections are now a leading cause of Healthcare Associated Infection (HAI). A significant concern is the spread of resistance to the antibiotic vancomycin which is a major driver in the generation of multiresistant strains. Enterococci utilise a pheromone-induced plasmid conjugation system for the transfer resistance genes into non-resistant cells. This Horizontal Gene Transfer (HGT) process is based around the ability of donor and recipient bacteria to communicate via a peptide pheromone system. Plasmid-free bacteria produce the pheromones and resistance gene transfer is initiated by binding of pheromones to cell surface receptors on plasmid-containing strains. Similar peptide based communication systems have also been reported in other Gram positive bacteria including pathogenic members of the genera Streptococcus and Bacillus. These peptide communication systems appear to be specific for each genus. Therefore pheromone-receptor binding has the potential to function as novel detection system and this will be investigated in this project.

Methods to be used

The Microbiology group have been studying pheromone based communication in enterococci for a number of years. Vancomycin resistant strains from both clinical and environmental sources are available their ability to transfer resistance genes under a variety of different conditions has been determined. Whole genome sequences of  selected enterococcal strains have been generated to in order to more fully characterise the pheromone communication machinery. The project builds upon a series of successful PhD projects within the Microbiology group and consequently the majority of techniques to be used (DNA and RNA extraction, analysis and sequencing; q-RT-PCR gene expression analysis; synthetic peptide chemistry; proteomics; antibiotic resistance profiling and bacterial conjugation assays) are well established.

Full training will be provided in these and other relevant techniques to enable the candidate to successfully complete the programme of research. We hypothesise that peptide pheromones, whose structure will be determined by analysis of our whole genome sequence libraries, can be artificially synthesised and will function in a similar manner to natural peptides. We will test this in a series of HGT systems that are currently in operation in the laboratory.  Once a set of peptide pheromones is identified these will be tested for their specificity by attaching fluorescent dyes and screening against panels of gastrointestinal bacteria. If, as expected, the binding of these peptide pheromones is shown to be species specific these will be examined for inclusion as detection ligands in a variety of diagnostic platforms: agglutination, ELISA and Lateral Flow systems. Impact Tackling antibiotic resistance is a World Health Organisation priority that requires a multifactorial approach. One of the major contributors to resistance is inappropriate antibiotic are prescribing. This is a consequence of poor diagnostic systems. This project will provide new diagnostic targets for incorporation into a variety of platforms. This project will be based at Ulster's Innovation Centre for Food and Health (NICHE).

References:

Conwell M, Daniels V, Naughton PJ, and Dooley, JSG. Interspecies transfer of vancomycin, erythromycin and tetracycline resistance among Enterococcus species recovered from agrarian sources. BMC Microbiology. 2017. Vol 17. Article 19

Increased sporulation underpins adaptation of Clostridium difficile strain 630 to a biologically–relevant faecal environment, with implications for pathogenicity. Ternan NG, Moore N, Smyth D, McDougall G, Allwood JW, Verrall S, Gill CIR, Dooley JSG, and McMullan G. 2018. Scientific Reports 8: 16691.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

  • Sound understanding of subject area as evidenced by a comprehensive research proposal

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.

  • Completion of Masters at a level equivalent to commendation or distinction at Ulster
  • Experience using research methods or other approaches relevant to the subject domain
  • Work experience relevant to the proposed project
  • Publications - peer-reviewed
  • Publications record appropriate to career stage
  • Experience of presentation of research findings
  • A comprehensive and articulate personal statement
  • Use of personal initiative as evidenced by record of work above that normally expected at career stage.
  • Relevant professional qualification and/or a Degree in a Health or Health related area

Funding and eligibility

The University offers the following levels of support:

Vice Chancellors Research Studentship (VCRS)

The following scholarship options are available to applicants worldwide:

  • Full Award: (full-time tuition fees + £19,000 (tbc))
  • Part Award: (full-time tuition fees + £9,500)
  • Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

  • Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
  • Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
  • Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
  • Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living

The Doctoral College at Ulster University

Key dates

Submission deadline
Friday 7 February 2020
12:00AM

Interview Date
9 to 20 March 2020

Preferred student start date
Mid September 2020

Applying

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Contact supervisor

Professor James Dooley

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