PhD Study : The role of dietary fatty acids and the gut microbiota on autoimmunity

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Summary

The aetiology of autoimmune disease is largely unknown albeit environmental factors including an individual’s diet have an important role in the optimal function of the immune system and inflammatory pathways. One such environmental factor is mercury (Hg) (Crowe et al, 2018). Humans are primarily exposed to methylmercury (MeHg) from fish consumption. Fish also contain beneficial nutrients, including polyunsaturated fatty acids (PUFAs) which have been demonstrated to benefit autoimmune and inflammatory disorders. Research by our group has identified associations between MeHg exposure and markers of autoimmune disease but only when models were controlled for PUFA, specifically n-3 PUFA (McSorley et al, in press). More recently, research has supported a role for the microbiome in the pathogenesis of autoimmune diseases (De Luca & Shoenfeld, 2017; Kim et al, 2016). The microbiome is proposed to alter the toxicity of MeHg (Rothenberg et al, 2019) and the microbiome may be favourably modified by dietary PUFA (Wolters et al, 2019). Furthermore, PUFA are able to modulate the function of immune cells in the intestine and other tissues and have an important role in autoimmune and inflammatory disorders. PUFA of both the n-6 and n-3 families are clinically useful in human autoimmune-inflammatory disorders, but the precise mechanisms by which these fatty acids exert their clinical effects are not well understood. Therefore, this PhD project aims to investigate the association between MeHg and/or PUFA and autoimmunity taking into consideration alternations in the microbiome at low and high concentrations of MeHg and PUFA.

Study 1: A systematic review will be undertaken to investigate the relationship between PUFA and autoimmunity.

Study 2: To investigate associations between MeHg and PUFA status and markers of autoimmunity in a high fish eating population in the Seychelles.

Study 3: To investigate the microbiome of individuals who are frequent consumers of fish in relation to PUFA status and MeHg exposure. This project will further look at assocaitions with health outcomes including autoimmune disease. Shotgun metagenomics sequencing will be undertaken to determine the relative abundance of microbial genes present and determine the potential holistic metabolic functionality of the microbiota with a particular focus on mercury metabolism.

Study 4: To investigate the impact of MeHg exposure on the composition and functionality of the microbiota using in vitro faecal batch culture experiements. A diverse range of high/low MeHg containing fish will be incubated in faecal batch fermenters and the changes to the metabolic functionality will be determined with a particular focus on identifying mercury demethylating potential.

References

Crowe W, Allsopp PJ, Watson GE, Magee PJ, Strain JJ, Armstrong DJ, Ball E, McSorley EM. Mercury as an environmental stimulus in the development of autoimmunity - A systematic review. Autoimmun Rev. 2017 Jan;16(1):72-80. doi: 10.1016/j.autrev.2016.09.020. Epub 2016 Sep 23. Review.

De Luca F, Shoenfeld Y.The microbiome in autoimmune diseases. Clin Exp Immunol. 2019 Jan;195(1):74-85. doi: 10.1111/cei.13158. Review.

Kim JW, Kwok SK, Choe JY, Park SH. Recent Advances in Our Understanding of the Link between the Intestinal Microbiota and Systemic Lupus Erythematosus. Int J Mol Sci. 2019 Sep 30;20(19). pii: E4871. doi: 10.3390/ijms20194871. Review.

Rothenberg SE, Wagner CL, Hamidi B, Alekseyenko AV, Andrea Azcarate-Peril M. Longitudinal changes during pregnancy in gut microbiota and methylmercury biomarkers, and reversal of microbe-exposure correlations. Environ Res. 2019 May;172:700-712. doi: 10.1016/j.envres.2019.01.014. Epub 2019 Jan 11.

Wolters M, Ahrens J, Romaní-Pérez M, Watkins C, Sanz Y, Benítez-Páez A, Stanton C, Günther K. Dietary fat, the gut microbiota, and metabolic health - A systematic review conducted within the MyNewGut project. Clin Nutr. 2019 Dec;38(6):2504-2520. doi: 10.1016/j.clnu.2018.12.024. Epub 2018 Dec 24. Review.

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

The Doctoral College at Ulster University

Key dates

Submission deadline
Friday 7 February 2020
12:00AM

Interview Date
9 to 20 March 2020

Preferred student start date
Mid September 2020

Applying

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Contact supervisor

Professor Emeir McSorley

Other supervisors