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

  • To hold, or expect to achieve by 15 August, an Upper Second Class Honours (2:1) Degree or equivalent from a UK institution (or overseas award deemed to be equivalent via UK NARIC) in a related or cognate field.
  • 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

    The University offers the following awards to support PhD study and applications are invited from UK, EU and overseas for the following levels of support:

    Vice Chancellors Research Studentship (VCRS)

    Full award (full-time PhD fees + DfE level of maintenance grant + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees and provide the recipient with £15,000 maintenance grant 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.

    Vice-Chancellor’s Research Bursary (VCRB)

    Part award (full-time PhD fees + 50% DfE level of maintenance grant + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees and provide the recipient with £7,500 maintenance grant 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.

    Vice-Chancellor’s Research Fees Bursary (VCRFB)

    Fees only award (PhD fees + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees 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.

    Department for the Economy (DFE)

    The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £15,285 per annum for three years. EU applicants will only be eligible for the fee’s component of the studentship (no maintenance award is provided). For Non-EU nationals the candidate must be "settled" in the UK. 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.

    Due consideration should be given to financing your studies; for further information on cost of living etc. please refer to: www.ulster.ac.uk/doctoralcollege/postgraduate-research/fees-and-funding/financing-your-studies



The Doctoral College at Ulster University


Reviews

Profile picture of Kamin Hau

Kamin Hau - PhD in Biomedical Sciences


Profile picture of Kieran O'Donnell

My experience has been great and the people that I have worked with have been amazing

Kieran O'Donnell - 3D printing of biological cells for tissue engineering applications

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Profile picture of Michelle Clements Clements

Completing the MRes provided me with a lot of different skills, particularly in research methods and lab skills.

Michelle Clements Clements - MRes - Life and Health Sciences

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Profile picture of Sarah Craig

I completed my undergraduate studies at Ulster University, where I graduated in 2017 with first class honours in Biomedical Science with a Diploma in Professional Practice . I joined the Diabetes Research group as a PhD researcher in September 2017 and completed my PhD studies in June 2020.I am proud to say I not only completed my PhD studies within 3 years, but also became the World Champion (with a perfect score!) in Irish Dance during my PhD studies. My favourite memory was the opportunity to present my PhD work at the EASD conference in 2019. If I could speak to myself at the start of my PhD, the best piece of advice I would give myself would be to enjoy every single minute as the time flies in. I really would do another PhD!

Sarah Craig - PhD in Biomedical Sciences


Profile picture of Natalie Klempel

I completed my undergraduate studies in America at Texas Woman’s University where I majored in Kinesiology. I then moved to Scotland to successfully complete my Masters with Merit in Human Anatomy at the University of Dundee.My proudest moment was when I passed my viva! My favourite memory was …the dissections. I’ll never forget the friends I made and the good times we had together. I couldn’t have got through this without the support of my family, friends, lab colleagues, supervisors, and my boyfriend. If I could speak to myself at the start of my PhD, the best piece of advice I would give myself would be to write up after every experiment, keep a lot of back up copies of the work, and to enjoy the experience.

Natalie Klempel - PhD in Biomedical Sciences


Profile picture of Poonam Singh Nigam

I joined Ulster university in Jan 1990 after completing Postdoctoral research in Germany (1986-88) and PhD in India (1985). DSc degree in Applied Microbial-Biotechnology has been awarded after the evaluation of my thesis based on Research, Publication & related activities, completed as a research-active academic member of staff (1990-2019). DSc thesis summarised my scientific outputs and contributions (183 research papers, 3 biotechnology reference-books, 43 research-informed book-chapters, 26 research-informed review-articles, 90 conference-abstracts,1 European Patent and 2 Technology-transfers; Supervision of National & International researchers-18 Postdoctoral/Exchange and 12 PhD; and affiliations as Examiner of 58 PhD researchers globally, and Fellow & Member of nine scientific & academic societies.My message to all researchers is that "Chase your Aspirations and Never Give up". I couldn’t have got through my long academic & Professional journey without

Poonam Singh Nigam - DSc in Biomedical Sciences


Profile picture of Karl Smith

I started my PhD after I completed my undergraduate in Biology at Ulster University in 2016, with a dissertation project that focused on genetic variations in bacterial species. I continued using some of these techniques in my doctoral research, which primarily involved the investigation and development of mass spectrometry imaging in vitamin D treated prostate cancer, looking at the metabolic and genetic variations upon treatment. I worked with international collaborators at the University of Edinburgh and Maastricht University, where I got to learn and develop mass spectrometry techniques that have not previously been carried out in Northern Ireland. I now work as a postdoctoral researcher at the National High Magnetic Field Laboratory at Florida State University in Tallahassee, Florida, where I am helping to develop and implement a mass spectrometry imaging facility for users across the world with the super powerful 21T FT-ICR mass spectrometer.A PhD is a demanding process but when

Karl Smith - PhD in Biomedical Sciences


Profile picture of William Crowe

Throughout my PhD I’ve been provided with continuous support and guidance by my supervisors and the staff at the University.I’ve also received many opportunities to further enhance my professional development in the form of teaching experience and presenting my work at conferences which will aid in my pursuit of a career in academia or industry.

William Crowe


Profile picture of Ryan Kelsey

I graduated Ulster University in 2016 with a degree in Biomedical Science with DPP (Pathology). I was then offered a PhD studentship with Dr Catriona Kelly and Professor Neville McClenaghan at CTRIC which I started in September 2016. My PhD explored the pathophysiology of Cystic Fibrosis-Related Diabetes, the most common co-morbidity associated with Cystic Fibrosis.My proudest moment was undoubtedly passing my Viva (via Skype!), but I was also proud to be given the opportunity to present my work at the UK Cystic Fibrosis Trust Conference in 2018. Through this conference, I was able to meet with people with CF and the challenges they face which was important reminder that the research I was doing mattered. I couldn't have got through this without the unwavering support of my family, who were always there for me in the good times and the bad. I am also extremely grateful for the support and mentorship of my supervisors Dr Catriona Kelly, Professor Neville McClenaghan and Dr Dawood Khan

Ryan Kelsey - PhD in Biomedical Sciences


Profile picture of Ahmed Abuelhana

My proudest moment was when I knew the possibility of the full transfer of my PhD project to Ulster University, the University which I loved and started my first steps towards my PhD in, and also being a PhD graduate from one of the highly reputable universities such as Ulster is a big thing which I should always be proud of. I think there is no that word that can ever express my deepest thanks and sincere appreciation to my supervisor Professor Kathryn Burnett for her ideal supervision, valuable guidance, encouragement, generous help and ultimate support throughout my PhD project. I have been really lucky to have her as a supervisor. Also my deepest gratitude to Mr Linden Ashfield, Principal Clinical Pharmacist, Antrim Area Hospital (NHSCT) for his help and endless support throughout the whole research project. Also, I could not have got through this without the support of my beloved family (my father ”Sayed”, my mother ”Gamila”, my wife “Nermeen”

Ahmed Abuelhana - PhD in Biomedical Sciences


Profile picture of Ryan Lafferty

I graduated from Queen's University Belfast with a Master's in pharmacy in 2014 and subsequently began working as a community pharmacist in the Greater Belfast area. My career began to take an unusual turn when I got involved with a small startup company who developed a novel blood glucose monitor for diabetic patients. From here, my interest in diabetes was piqued and I applied for a PhD project (somewhat optimistically!) in the Diabetes Research Group at Ulster. Nearly four years later, I'm still there working as a postdoctoral researcher. Not bad considering I never thought I had a chance of getting a PhD spot!My time within the DRG has been, and still is, fantastic. I've made life-long friends (and surprisingly few enemies!) who have been patient, helpful and a joy to collaborate with. I couldn't have got through it without them (you know who you are). Likewise, the guidance from my supervisors, Prof. Peter Flatt and Dr. Nigel Irwin, has been invaluable. I'm probably most proud of

Ryan Lafferty - PhD in Biomedical Sciences