About the Project
The obesity and type 2 diabetes epidemic, fuelled by over-nutrition and an aging global demographic, is so advanced that, as a result, almost every country will soon struggle with the major financial and healthcare implications [1]. Accordingly, new approaches to curtail obesity and related diabetes are of considerable therapeutic interest. Gastrointestinal tract (GIT)-derived hormones have long been recognised as a source of new targets for obesity and diabetes [3]. This is highlighted by the successful clinical development of long-acting GLP-1 mimetics [4]. Despite the vigour with which GLP-1 mimetics have been adopted into the diabetic clinic, weight loss and metabolic control are not as impressive as first hoped [4]. In this regard, several recent studies reveal that dual activation of CCK1 and GLP-1 receptors has marked synergistic metabolic and weight reduction benefits [5-7]. Thus, there is much excitement regarding the potential therapeutic value of the novel CCK1 and GLP-1 receptor dual agonist hybrid peptide, (pGlu-Gln)-CCK-8/exendin-4, for obesity and related diabetes as indicated by our recent publication in the top ranking journal Diabetes [8]. This hybrid peptide facilitates formulation and dosing with a single molecule, while still allowing for co-activation of CCK1 and GLP-1 receptors, to deliver the full synergistic metabolic and weight-lowering benefits [2,5-8].
To extend this research and progress a possible new drug target for diabetes, we propose to capitalise on the development of (pGlu-Gln)-CCK-8/exendin-4 hybrid in our laboratory. This will include generation of fatty acid derived and PEGylated hybrid peptides to extend pharmacodynamic profile, assessment of beneficial metabolic effects in animal models of type 2 diabetes with diverse aetiologies and uncovering the fundamental mechanisms of action. The over-arching hypothesis is that derivatives of (pGlu-Gln)-CCK-8/exendin-4 offers distinct therapeutic promise for people living with type 2 diabetes.
Closing date for Applications is 26 February 2016.
Funding Notes
Department for Employment and Learning Research Studentships (DEL)
The University has DEL research studentships available for PhD projects (these pay tuition fees and an annual maintenance award of not less than £14,052 per annum). Eligibility criteria can be found here; http://www.ulster.ac.uk/__data/assets/pdf_file/0010/73747/Eligibility.pdf
Terms and Conditions can be found here; http://www.ulster.ac.uk/__data/assets/pdf_file/0009/73746/DEL-Postgraduate-Terms-Conditions-1516.pdf
Vice-Chancellor's Research Scholarships (VCRS)
A number of University funded VCRS will be available for PhD projects at Ulster (these cover tuition fees and a maintenance award of not less than £14,057 per annum for three years, subject to satisfactory academic performance). Details on eligibility can terms and conditions can be found here; https://www.ulster.ac.uk/__data/assets/pdf_file/0005/77162/Awards-available-for-Overseas-Students-Jan-16.pdf
References
1. Imes CC, Burke LE. The Obesity Epidemic: The United States as a Cautionary Tale for the Rest of the World. Curr Epidemiol Rep. 2014 Jun 1;1(2):82-88.
2. Irwin N, Flatt PR. Enteroendocrine hormone mimetics for the treatment of obesity and diabetes. Curr Opin Pharmacol 13:989-95, 2013.
3. Field BC, Wren AM, Cooke D, Bloom SR. Gut hormones as potential new targets for appetite regulation and the treatment of obesity. Drugs. 68(2):147-63, 2008
4. Sadry SA, Drucker DJ. Emerging combinatorial hormone therapies for the treatment of obesity and T2DM. Nat. Rev. Endocrinol 9:425-33, 2013.
5. Irwin N, Hunter K, Montgomery IA, Flatt PR. Comparison of independent and combined metabolic effects of chronic treatment with (pGlu-Gln)-CCK-8 and long-acting GLP-1 and GIP mimetics in high fat-fed mice. Diabetes Obes. Metab 15:650-9, 2013.
6. Trevaskis JL, Sun C, Athanacio J, D'Souza L, Samant M, Tatarkiewicz K, Griffin PS, Wittmer C, Wang Y, Teng CH, Forood B, Parkes DG, Roth JD. Synergistic metabolic benefits of an exenatide analogue and cholecystokinin in diet-induced obese and leptin-deficient rodents. Diabetes Obes Metab 17:61-73, 2015.
7. Chen Y, Song M, Liu F, Lockwood J, Alsina J, Hammond C. CCk8 Enhances Anti-diabetic Efficacy of GLP1. The FASEB Journal. 27:1160.3, 2013
8. Irwin N, Pathak V, Flatt PR. A novel CCK-8/GLP-1 hybrid peptide exhibiting
Continue with Facebook
