PhD Study : Elucidating the role of kisspeptin related peptides in pancreatic beta-cell function and survival

Summary

Kisspeptin is a 54 aa hypothalamic peptide that activates G protein-coupled KISS1 receptors. However, the physiological function of kisspeptin is not confined to the hypothalamus, as the hormone and its receptor are abundantly expressed in various tissues, including the endocrine pancreas. Kisspeptin has been shown to stimulate insulin secretion from beta-cells.

Furthermore, there is knowledge that kisspeptin can affect cell survival and proliferation. Whether this extends to survival and proliferation of pancreatic beta-cells, with obvious beneficial effects for diabetes, remains to be elucidated. Moreover, further understanding of the role of kisspeptin in the pathophysiological progression of diabetes, could uncover important, therapeutically relevant, information. Kisspeptin is proteolytically processed into several smaller fragments that have been isolated in humans composed of 10, 13 and 14 aa.

Each of these fragments has a conserved C-terminal region, highlighting this as an important region of the molecule for receptor binding and biological actions. Indeed, all four peptides, kisspeptin 10, 13, 14 and 54, possess the same affinity for the KISS1 receptor, and have been shown to be biologically active. This is particularly encouraging, as smaller peptides are easier to synthesise and formulate, less expensive and much more favourable drug candidates.

Taken together, uncovering the mechanisms involved in kisspeptin degradation, its role in diabetes progression together with the direct effects of kisspeptin and related fragments on beta-cell function and survival could help reveal a novel therapeutic strategy for the treatment of diabetes. This would ultimately be accomplished through synthesis of long-acting kisspeptin related peptides, where the diabetes research group at Ulster have notable relevant experience.

The core objectives of this research project are therefore:

• Determine the full degradation profile of kisspeptin;
• Characterise novel and long-acting kisspeptin and kisspeptin fragment peptides;
• Assess in vitro biological actions of novel peptides in rodent and human insulin-releasing cell lines (BRIN-BD11 and 1.1B4) and isolated mouse islets under normal and diabetic conditions;
• Determine effects of kisspeptin peptides on beta-cell proliferation and apoptosis under normal and diabetic conditions;
• Uncover the role of kisspeptin in the progression of diabetes; *Establish in vivo gluco-regulatory and insulin secretory actions of novel peptides; *Determine biological duration of action/toxicity of novel peptides;
• Finally, assess beneficial effects of novel peptides alone, and in combination with established antidiabetic drugs, in models of type 2 diabetes with different aetiologies.

This PhD 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 sciences, pharmacology or a related subject would be desirable. Informal enquiries to Profesor Gault (va.gault@ulster.ac.uk) are welcomed.

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
• Sound understanding of subject area as evidenced by a comprehensive research proposal
• 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