PhD Study : Targeting kisspeptin for the treatment of metabolic diseases

Summary

Kisspeptin is a 54 amino acid hypothalamic peptide hormone that activates KISS1 receptors. However, the physiological function of kisspeptin is not confined to the hypothalamus, as the hormone and its receptor are expressed in various tissues, including the endocrine pancreas and liver. Kisspeptin has been shown to stimulate insulin secretion from beta cells. More recent evidence suggests that activation of hepatic KISS1 receptors can ameliorate non-alcoholic fatty liver disease (NAFLD). Thus, kisspeptin represents an exciting target for the treatment of diabetes, obesity and NAFLD. However, as with many peptide hormones, kisspeptin is proteolytically processed into several smaller fragments. Uncovering the mechanisms involved in kisspeptin degradation together with its role in the progression of metabolic diseases, could help reveal, an as yet untapped, therapeutic promise.

Therefore, we will address the following research questions:

1)What impact do kisspeptin peptides have on pancreatic beta-cell function? We will determine full enzymatic degradation profile of kisspeptin and assess secretory and functional effects of kisspeptin peptides on pancreatic beta-cells.

2)Can long-acting enzyme resistant forms of kisspeptin be generated that maintain biological activity? Using knowledge gained from question 1, we will synthesise enzyme resistant forms of kisspeptin and confirm bioactivity. The most promising analogues will be progressed to in vivo studies for examination of effects on satiety and glucose homeostasis.

3)What impact will enzymatically stable kisspeptin peptides have on metabolic control? Preclinical therapeutic effectiveness of lead kisspeptin peptides will be studied in models of diabetes.

In addition, we will employ mice fed a high fat diet to assess how the hepatic KISS1R can prevent liver fat accumulation. Expected Results:  Based on the literature, KISS1R modulation will positively impact beta-cell function. We are also confident that sustained activation of hepatic KISSR will exert direct measurable benefits in NAFLD.

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

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