PhD Study : Investigation of oral and blood microbiome shifts in patients with depression.

Summary

Background:

A growing body of evidence now supports an important role for the human gut microbiome in modulating brain function and promoting depression and other psychiatric disorders via the vagus nerve and other biological mechanisms (1). To date, the importance of the oral microbiota in mental health has received little attention, even though it is one of the most diverse microbiomes in the human body, and oral dysbiosis has been linked not only to oral disease, but also many other systemic diseases with an underlying inflammatory aetiology, such as cardiovascular disease (CVD) (2). Furthermore, inflammatory disease-associated perturbations in the oral microbiome can also mirror dysbiotic changes in the gut, and normalisation based on therapeutic intervention can help identify treatment responders (3). As the mouth is highly vascularized, bacteraemia due to bacterial translocation across the epithelial mucosa is an everyday event. This ‘mobile microbiome’ has the potential to cause metastatic infection, injury and inflammation. The recent and exciting demonstration of a dormant blood microbiome that is disturbed in patients with CVD versus healthy controls further highlights the importance of haematogenous spread of bacteria and the development of disease at distal sites (4). Activation of microglial immune cells in the brain may therefore result from bacterial organisms and their products, as well as systemic inflammatory molecules, crossing a compromised blood-brain barrier (BBB), and leading to chronic brain inflammation that appears linked to depressive symptoms (5).

Project aims:

This is a highly topical and innovative project in the field of mental health research that will map the oral and blood microbiomes in patients with depression, thus providing potential new insights into the underlying biological bais of depression, and identifying novel diagnostic signatures of the disease.

The PhD student will focus on three main areas:

1.The collection saliva and blood samples from patients who meet the DSM-IV criteria for moderate or severe depression, as well as matched healthy controls. We have already conducted a small feasibility study to compare the oral microbiome in depressed individuals and healthy controls (n=40 per group) highlighting the viability of the project.

2.16S rDNA and shotgun metagenomic sequencing, followed by taxonomic and functional classifications, for the potential discovery of novel microbial-based biomarkers of depression.

3.Mechanistic in vitro studies with different brain cell types to understand how interactions with specific oral bacteria and their products crossing a leaky or permeable BBB could contribute to symptoms of depression and anxiety.

Project techniques:

The project will provide the student with training in a wide range of highly transferable laboratory techniques: These include: Molecular Biology (DNA extraction, PCR/qPCR, Next generation sequencing); Biochemistry (Protein and Metabolite analysis), Cell culture, Bioinformatics.

Researcher will be based at C-TRIC (Altnagelvin Hospital site).

References:

1.Foster JA, Lyte M, Meyer E, Cryan JF. Gut Microbiota and Brain Function: An Evolving Field in Neuroscience. Int J Neuropsychopharmacol. 2016 19(5).

2.Pietiainen M, Liljestrand JM, Kopra E, Pussinen PJ. Mediators between oral dysbiosis and cardiovascular disease. Eur. J. Oral. Sci. 2018 (126): 26-36.

3. Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat. Med. 2015 (8):895-905.

4. Amar J, Lange C, Payros G, Garret C, Chabo C, Lantieri O, et al. D.E.S.I.R. Study Group. Blood microbiota dysbiosis is associated with the onset of cardiovascular events in a large general population: the D.E.S.I.R. study. PLoS One. 2013;8(1):e54461.

5. Holmes SE, Rainer H, Conen S, Gregory CJ, Matthews JC, et al. Elevated Translocator Protein in Anterior Cingulate in Major Depression and a Role for Inflammation in Suicidal Thinking: A Positron Emission Tomography Study. Biol. Psych. 2018; 83:61-69.

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