Elucidating the role of gut hormones in infertility associated with diabetes, obesity and PCOS

Summary

The rising prevalence of obesity and diabetes has had a profound negative impact on female reproductive health. Increased body mass index (BMI) is associated with ovulatory subfertility and anovulatory infertility. A large proportion of infertile women have polycystic ovary syndrome (PCOS) which is also linked to increased risk of diabetes, obesity and other metabolic anomalies. The association between obesity and/or PCOS and hyperinsulinaemia, hyperandrogenism and abnormal hormone secretion, underlies many reproductive disorders.

Increasing evidence supports the hypothesis for a key role for derangements in gut hormones in both the metabolic and fertility disturbances associated with obesity and diabetes. Research on involvement of gut hormones in reproductive function is scant, although gut hormone receptors and/or actions have been demonstrated on pituitary, adrenal cortex, gonads and CNS.

The proposed project seeks to assess the direct effects of GLP-1, PYY, ghrelin and GIP on  pituitary cells, and effects of GIP on steroidogenesis on adrenal cortical cells.

Core aims of the proposed research are:

*Using a pituitary cell line, the direct effects of GLP-1, PYY and ghrelin will be assessed in vitro.

*Immunocytochemical staining for GLP-1, NPY, GIP and ghrelin receptors will verify their presence on the cells.

*LH and FSH will be measured to assess the effects of gut hormones on gonadotropes.

* In vitro studies using human adrenal corticocarcinoma NCI-H295R cells will be carried out to assess the effects of GIP on steroidogenesis in the adrenals.

*Using ELISA, cortisol, testosterone, estradiol and DHT will be measured to assess the effects of GIP on steroid production.

*Using RT-PCR and Western blotting, the expression of several genes involved in steroid production and GIP receptors will be quantitatively analysed.

*Immunocytochemical staining for GIP receptors will further demonstrate their presence in NCI-H295R cells.

*In vivo studies will be conducted to investigate the effects of these peptides on metabolic function, oestrus cycling and reproductive function in animal models of obesity and infertility.

This project will provide excellent training in a wide range of state-of-the-art research techniques. We are seeking an applicant with good practical laboratory, computer and communication skills and enthusiasm and commitment to work diligently on all aspects of the research project. A background in biomedical, biological sciences, nutrition, pharmacology or a related subject would be desirable.

This is one of three top priority projects for Ulster’s Diabetes Research Group. The proposed work (ring-fenced studentship) is part of a programme of research carried out by Dr Moffett’s team funded by a major grant from Diabetes UK. Informal enquiries to  cr.moffett@ulster.ac.uk are welcomed.

Essential criteria

• Upper Second Class Honours (2:1) Degree or equivalent from a UK institution (or overseas award deemed to be equivalent via UK NARIC)

• 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.

• First Class Honours (1st) Degree
• Masters at 65%
• Research project completion within taught Masters degree or MRES
• Practice-based research experience and/or dissemination
• Experience using research methods or other approaches relevant to the subject domain
• Work experience relevant to the proposed project
• Publications - peer-reviewed
• 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

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 studentship 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 studentship 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 studentship 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 £ 15,009 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 studentship 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