PhD Study : Mechanisms of islet adaptation in pregnancy: impact of estrogen and progesterone on pancreatic β-cell energy metabolism

Summary

One of the causes of type 2 diabetes is a defect of β-cells that reside in islets of Langerhans within the pancreatic gland. The excessive demands for insulin from obese or ageing body are believed to impair the biochemical reactions linking glucose to ATP, the main ‘energy currency’ of a living cell thereby unbundling the stimulus (glucose) from secretion (insulin). The mechanisms of the defect are difficult to study, as it becomes detectable at a late stage of the disease. Pregnancy presents a natural equivalent of diabetes, that comes and goes: an increasing insulin demand makes some mothers-to-be temporally diabetic. Gestational diabetes is observed in experimental animals (mice) and hence can be studied in the laboratory. Despite obvious importance for people with diabetes, little is known about the how and how fast the elevated body weight and levels of circulating ‘pregnancy hormones’, estrogen and progesterone, change glucose handling in β-cells.

Our hypothesis is that pregnancy temporarily makes β-cell energy-related reactions more sensitive to glucose, thereby increasing insulin secretion when needed. This comes at a price of damage to main energetic organelle, mitochondria. We aim to test the hypothesis by imaging how the biochemical reactions induced by glucose progress in pregnant mice or islets that were kept at high concentrations of estrogen/progesterone.

Using fluorescence microscopy we will study:

1.How glucose impacts cellular energy metabolites, such as fructose-1,6-bisphosphate, ATP, NAD(P)H, different forms of oxygen in islets from mice with gestational diabetes.

2.How physiologically important compounds (glucose, GLP-1, GIP, somatostatin) impact intracellular signals (Ca2+ and cAMP). We will also assess:

3.Hormone secretory function and

4.Food intake, body weight, blood insulin and glucose of the experimental mice.

We expect to get a detailed information on changes in islet biochemistry in pregnancy and elucidate how and how fast they are induced.

Please note: Applications for more than one PhD studentship 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
• 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

Equal Opportunities

The University is an equal opportunities employer and welcomes applicants from all sections of the community, particularly from those with disabilities.

Appointment will be made on merit.

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 £19,237 (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