PhD Study : The role of Clostridium difficile biofilm ultrastructure in disease persistence

Summary

C. difficile is a multiply antibiotic resistant bacterial gut pathogen and is the most common cause of diarrhoeal disease in vulnerable patients.  C. difficile infection (CDI) generally occurs after a patient has been on a course of antibiotics and the disease can cause significant morbidity and mortality in infected patients.  While C. difficile infection and pathogenesis is mediated primarily by gut damaging toxins A and B produced by the organism, the role of gut colonisation and biofilm formation have also been suggested to contribute not only to pathogenesis but also to the persistence and recurrence of C. difficile infections.  This aspect of the organism’s pathogenesis is not well studied, but we hypothesise that biofilms in the gut play a key role in disease recurrence. The extent of biofilm formation by C. difficile strains varies, suggesting that a multiplicity of as yet uncharacterised factors are likely to be involved.

The objective of this project is to investigate changes in ultrastructural physiology and gene expression associated with, and leading to, C. difficile biofilm development. A combination of state of the art molecular biology and 3D bioimaging methods will be used to build upon recent data from our lab showing that disruption of the dnaK gene significantly enhances C. difficile biofilm formation. This dnaK mutant represents an excellent “enhanced biofilm former” which can be used in our experiments to examine more fully the changes in biofilm structure and development.

In this project, our original approach will facilitate exploration of the role of a variety of factors – antibiotic sensitivity, cell surface structure, hydrophobicity, motility, communication, response to gut metabolites – that will lead to a more precise definition of the mechanisms underlying C. difficile biofilm formation during disease.

Please note: Applications for more than one PhD studentship are welcome, however if you apply for more than one PhD project within Biomedical Sciences, your first application on the system will be deemed your first-choice preference and further applications will be ordered based on the sequential time of submission. If you are successfully shortlisted, you will be interviewed only on your first-choice application and ranked accordingly. Those ranked highest will be offered a PhD studentship. In the situation where you are ranked highly and your first-choice project is already allocated to someone who was ranked higher than you, you may be offered your 2nd or 3rd choice project depending on the availability of this project.

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
• Clearly defined research proposal detailing background, research questions, aims and methodology

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 record appropriate to career stage
• Experience of presentation of research findings
• A comprehensive and articulate personal statement
• 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