PhD Study : Harnessing novel bacterial peptides for antibiotic delivery in the gut microbiome

Summary

Emergence of antimicrobial resistance (AMR) has been, recognized as a problem of global proportions, because it leads to increasing numbers of opportunistic pathogens and renders conventional treatment of bacterial infections ineffective.  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 antibacterial agents. Our research strategy is to investigate a specific bacterial communication system and assess its suitability as a delivery mechanism for antimicrobials.

The project builds on a series of successful PhD projects within our group. We have been isolating antibiotic resistant bacteria from the human gut to understand the selection pressures that are in operation promoting horizontal gene transfer (HGT) of antibiotic resistance genes. We have focused on antibiotic resistant gut bacteria of the genus Enterococcus which are increasingly being recognised as significant agents of Healthcare Associated Infection (HAI). They are associated with conditions such as urinary tract infection, endocarditis and septicaemia.

Our strains exhibit high level, resistance to the antibiotic Vancomycin, one of the last line of effective drugs available and only used when other treatment options have been exhausted. We have shown that these strains can pass on genes for vancomycin resistance to other bacterial strains by a process of conjugation thereby greatly exacerbating the problem. This important process of HGT is controlled by a very specific communication system that employs unique peptides. The peptides are produced by antibiotic sensitive strains, that potentially can receive resistance genes, and they bind to strains that harbour resistance genes and prime them for transfer.

These observations have allowed us to formulate a hypothesis that laboratory synthesised peptides would mimic the activity of the natural ones. These could then be employed in two ways; (1) they could be chemically altered such that they would interfere with the bacterial communication system and prevent HGT of vancomycin resistance genes and, (2) they could be linked to specific antibiotics and used to target vancomycin-resistant strains of Enterococcus. These short peptides can easily be synthesised in the laboratory and our group has previously been successful in demonstrating that laboratory synthesised-peptides retain biological activity. The aim of this project would be to synthesise a series of peptides that are known to be used by Enterococcus species. These will be labelled with fluorescent markers and used to directly demonstrate binding to target strains.

Once binding has been established a variety of alterations will be made to the peptides and the effects on binding and HGT will be determined in a series of well-established laboratory assays. Finally, the peptides will be, chemically cross-linked to a set of antibiotics to assess the suitability of the system to specifically deliver the drugs to a single bacterial species.

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

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
• 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 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