The obesity and type 2 diabetes epidemic are becoming so advanced that almost every country will struggle with the major financial and healthcare implications. Accordingly, new approaches to curtail obesity and related diabetes are of considerable therapeutic interest. In this regard, regulatory hormones derived from either the pancreas or the gastrointestinal tract (GIT) have long been recognised as a source of new drug targets for obesity-diabetes. This is highlighted by the recent successful clinical application of glucagon-like peptide-1 (GLP-1) mimetics for both obesity and diabetes. In addition, recent FDA approval of a hybrid peptide with dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor modulating actions for diabetes, demonstrates antidiabetic efficacy of peptide therapies beyond GLP-1. As such, neuropeptide Y receptors (NPYR), activated by members of the NPY peptide family including Peptide YY (PYY) and Pancreatic Polypeptide (PP), can induce weight loss and/or improve pancreatic islet function.
At Ulster, we have developed patent protected PYY and PP molecules that exert direct benefits on pancreatic beta-cell function and promote reductions in energy intake. Moreover, we have published and unpublished data to demonstrate clear antidiabetic efficacy of these PYY and PP compounds both alone, and in combination with GLP-1 mimetics.
Utilising this new knowledge, the following research objectives will be addressed as part of this PhD project
These include:
*Assess the in vitro enzymatic stability of novel PP and PYY peptides
*Consider design of enzymatically stable dual-acting GLP-1 and NPY receptor hybrid peptides
*Examine biological actions of novel PYY and PP peptides in BRIN BD11 cells and perfused isolated mouse islets
*Establish in vivo satiety effects as well as glucose-regulatory and insulin secretory actions of all test peptides
*Assess the beneficial effects of combined GLP-1 and NPY receptor activation in rodent models with different aetiologies of diabetes
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.
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