Clinical and Molecular Investigation of GCPR Pathway Modulation by Omega-3 Fatty Acids in Insulin Resistance, Prediabetes and Type 2 Diabetes

Summary

A greater understanding of preventive and therapeutic strategies for obesity and type 2 diabetes (T2DM) is needed.

Early intervention and lifestyle adjustments can slow, stop and even reverse prediabetes. While omega-3 polyunsaturated fatty acids (PUFAs) are known for cardiovascular benefits, their effects on T2DM remain less clear.

Free-fatty-acid G-protein coupled receptors (GPCRs) play a role in counteracting early islet-cell dysfunction, impaired insulin secretion, insulin resistance and inflammation in T2DM.

Our research shows that omega-3 PUFA receptors in pancreatic islets and intestinal cells promote glucose-lowering, insulinotropic, and incretin effects, while also reducing risk and improving metabolic control in obesity, and type 2 diabetes.

This studentship will validate omega-3’s benefits on energy expenditure, fuel utilization and incretin release in metabolic disease.

Our aims are to: investigate GPCR-targeted omega-3 therapy on diabetes progression in pre-clinical studies using knockout models; define omega-3-induced GPCR-signalling mechanisms in peripheral tissues using CRISPR/Cas9 gene-editing; and assess the metabolic effects of PUFAs in humans with T2DM.

This research will provide excellent translational research training, strengthen understanding of druggable GPCR pathways to support future personalized therapies and drug development.

The studentship aims to investigate:

1. The therapeutic effects of naturally occurring omega-3 polyunsaturated fatty acids (PUFAs) that selectively target G protein-coupled receptors (GPCRs), focusing on their role in modulating metabolic and inflammatory pathways in early-onset diabetic models and GPCR-knockout models
2. Gene knockout of GPCRs using CRISP-R gene editing, fluorescence microscopy, mass spectrometry, PCR and western blotting to investigate the common receptor-mediated downstream signalling molecules activated in diabetes and cardiovascular disease.
3. The anti-diabetic and anti-inflammatory effects of GPCR activation by naturally occurring omega-3 polyunsaturated fatty acids in clinical studies in patients with obesity, prediabetes and type 2 diabetes

Important Information: 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
• A comprehensive and articulate personal statement

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
• 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

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

This project is funded by:

• Department for the Economy (DfE)

This scholarship will cover tuition fees and provide a maintenance allowance of £21,000* (tbc) per annum for three years (subject to satisfactory academic performance).  A Research Training Support Grant (RTSG) of approximately £900 per annum is also available.

To be eligible for these scholarships, applicants must meet the following criteria:

• Be a UK National, or

• Have settled status, or

• Have pre-settled status, or

• Have indefinite leave to remain or enter, or

• be an Irish National

Applicants should also meet the residency criteria which requires that they have lived in the EEA, Switzerland, the UK or Gibraltar for at least the three years preceding the start date of the research degree programme.

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.

*Part time PhD scholarships may be available, based on 0.5 of the full time rate, and will require a six year registration period