This project is funded by:
New and highly effective drugs for the treatment of obesity and diabetes, such as liraglutide (Victoza®, Saxenda®), semaglutide (Ozempic®, Wegovy®) and tirzepatide (Mounjaro®, Zepbound®) are essentially derived from products of the proglucagon and GIP genes. Despite the established effectiveness of these drugs, they have major patient compliance issues due to their adverse effect profile relating to severe nausea, vomiting and other gastrointestinal type problems. We believe that a more thorough investigation of other products from the proglucagon and GIP genes, of which there are well over 10 different entities, could yield new drugs that can enhance the effectiveness of these currently approved drugs whilst also limiting their detrimental adverse effect profile. This project could help make drugs such as semaglutide and tirzepatide more amenable to patients that will help improve metabolic benefits in the real world setting.
Therefore, the following research questions will be addressed as part of this research project:
1) What impact do proglucagon and GIP gene peptide products have on pancreatic beta-cell function? We will assess secretory and functional effects of all peptide products on pancreatic alpha- and beta-cells. We will also investigate the most effective peptide combinations in this regard.
2) Can long-acting enzyme resistant forms of proglucagon and GIP gene peptide products be generated? Using knowledge gained from question 1, we will synthesise enzyme resistant forms of lead peptides and confirm bioactivity. The most promising analogue combinations will be progressed to studies in animal models to examine effects on satiety and glucose homeostasis.
3) What impact will lead peptide combinations have on metabolic control? Preclinical therapeutic effectiveness of lead peptide combinations will be studied in models of obesity and diabetes. Expected Results: We expect to uncover treatment options to enhance the well-characterised benefits of currently approved drugs such as semaglutide and tirzepatide.
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.
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.
If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.
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.
This project is funded by:
Our fully funded PhD scholarships will cover tuition fees and provide a maintenance allowance of £19,237 (tbc) per annum for three years (subject to satisfactory academic performance). A Research Training Support Grant (RTSG) of £900 per annum is also available.
These scholarships, funded via the Department for the Economy (DfE) and the Vice Chancellor’s Research Scholarships (VCRS), are open to applicants worldwide, regardless of residency or domicile.
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.
Lafferty RA, Flatt PR, Gault VA, Irwin N. Does glucose-dependent insulinotropic polypeptide receptor blockade as well as agonism have a role to play in management of obesity and diabetes? J Endocrinol. 2024 Jul 15;262(2):e230339
Lassen MCH, Johansen ND, Modin D, Catarig AM, Vistisen BK, Amadid H, Zimmermann E, Gislason G, Biering-Sørensen T. Adherence to glucagon-like peptide-1 receptor agonist treatment in type 2 diabetes mellitus: A nationwide registry study. Diabetes Obes Metab. 2024 Nov;26(11):5239-5250.
Lafferty RA, Flatt PR, Irwin N. GLP-1/GIP analogs: potential impact in the landscape of obesity pharmacotherapy. Expert Opin Pharmacother. 2023 Apr;24(5):587-597.
Tanday N, Flatt PR, Irwin N. Amplifying the antidiabetic actions of glucagon-like peptide-1: Potential benefits of new adjunct therapies. Diabet Med. 2021 Dec;38(12):e14699.
Lafferty RA, O'Harte FPM, Irwin N, Gault VA, Flatt PR. Proglucagon-Derived Peptides as Therapeutics. Front Endocrinol (Lausanne). 2021 May 18;12:689678.
Submission deadline
Monday 24 February 2025
04:00PM
Interview Date
24 March - 4 April 2025
Preferred student start date
15 September 2025
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