As part of ongoing programme into natural antidiabetic drug discovery; we isolated several novel insulin-releasing antihyperglycaemic agents from amphibian skin secretion for the treatment of type 2 diabetes. We have developed novel analogues of previously described insulinotropic host defence peptides from Xenopus amieti, Hymenochirus boettger, Lithobates chiricahuensis, Sphaenorhynchus lacteus etc. and early results indicated structural modifications of these peptides resulted in a significant augmentation of the insulinotropic effects; producing enhanced in vitro insulinotropic effects as well as improved glucose tolerance and insulin release in obese insulin resistant mice.
The overall aim of this research is to examine the long-term metabolic effects and elucidate molecular mechanism of actions of novel peptide analogues of some recently discovered host defence peptides with potent insulin-releasing effects for potential development as novel type 2 diabetes drugs. The proposed research will investigate the interaction of novel peptides from amphibian skin secretion with beta-cell membrane proteins as well as in vivo changes in the expression of key genes and proteins involved in glucose signalling via the KATP-dependent and the cAMP-dependent secondary messenger pathways resulting from the administration of the peptides to diabetic animals.
This project will involve techniques such as HPLC, MALDI-TOF, tissue culture, small animal handling and experimentation, PCR, immunohistochemistry, flurometric assay, radioimmunoassay, etc. PCR and Western blotting will be utilised to explore both gene and protein expression of key elements involved in pathways of insulin secretion (such as Ins1, Gck, Kcnj11, Abcc8, Cacna1c), beta cell proliferation (such as Pdx-1) and insulin action (such as Irs1, Ptb1, Pi3kca, Pdk1, Akt1, Insr, Slc2a4).
The proposed research will provide training in a wide range of techniques.
Applicants should note that Laboratory bench fees of £6,000.00 per annum are required for this self-funded PhD 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.
Musale V, Guilhaudis L, Abdel-Wahab YHA, Flatt PR, Conlon JM (2019). Insulinotropic activity of the host-defense peptide frenatin 2D: Conformational, structure-function and mechanistic studies. Biochimie 156:12-21. 2.
Ojo O. O, Flatt P. R, Abdel-Wahab Y. H. A and Conlon J. M (2013). Insulin-Releasing Peptides. In: Handbook of Biologically Active Peptides (2nd Edition). Elsevier, pp. 364-370. ISBN 978-0-12-385095-9.
Submission deadline
Wednesday 1 September 2021
12:00AM
Interview Date
To Be Confirmed
Preferred student start date
To Be Confirmed
Telephone
Contact by phone
Email
Contact by email