PhD Study : Molecular dissection and identification of novel surface features/molecules involved in biofilm formation using a multi-disciplinary approach

Summary

​Bacteria grow in a self generated extracellular polymeric matrix, affording them protection from antimicrobials and extreme environmental conditions. Biofilms are not only difficult to eradicate, but allow development of antibiotic resistance by acquisition of anti-microbial resistance genes within existing biofilms. The issue is particularly problematic in chronic wounds where e.g. P aeruginosa numbers >10E6 will cause a chronic non healing persistent inflammatory state. Where conventional anti-biotic treatment fails, debridement or amputation may be necessary. Chronic wounds result in approximately 8000 patients undergoing amputation each year, at a cost to the NHS of more than £3bn annually. Therefore, any additional information on mechanisms and proteins controlling biofilm development, and potential means of disrupting this process is urgently required, and could assist in the development of treatment strategies.

Hypothesis:

Identification and localisation of key P aeruginosa cell surface components will allow rational design of novel interventions to perturb biofilm development.

Methods:

Assessment of Biofilm development: Biofilm development will be assessed and characterised using a novel multi-disciplinary approach. A combination of environmental scanning electron, confocal and atomic force microscopy will allow us to visualise and characterise biofilms grown under different conditions. A number of products associated with biofilm forming bacteria are present at or near the surface, including flagella, and surface proteins: (OmpC, pilins), and a variety of lipopolysaccharides.  Following visual characterisation, the same sample and field of view will be presented for mass spectrometry imaging. This will allow identification and localisation of these (surface lipids or metabolites) to characterise key biofilm components at a molecular level. Identification of key biofilm surface components.

Once identified, pathway screening will be conducted to identify the biological role these molecules play in biofilm formation. Further identification at the protein level will be conducted using in-solution shotgun proteomics approaches by liquid chromatography and high-resolution mass spectrometry. This will allow identification of key surface proteins domains and offer insights into biofilms formation mechanisms. Identification of such components within bacterial cells and/or the biofilm matrix will assist with the rational design of next generation anti-biofilm compounds.

Disrupting biofilm development ​

A number of potential anti-biofilm agents will be applied and tested at various stages of the biofilm development to determine their ability to disrupt key biofilm development molecules and ultimately biofilm development. In vitro models will be used initially, and once essential components have been identified we will attempt to use a tissue culture cell model to determine the potential for translation to the chronic wound environment.

Please note: Applications for more than one PhD studentships 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
• Sound understanding of subject area as evidenced by a comprehensive research proposal
• 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