Self-funded PhD opportunity Utilising venom from Tarantula spiders for diabetes drug discovery
Subject: Biomedical Sciences
Diabetes mellitus is reaching epidemic proportions globally, and despite the range of currently available anti-diabetes medications, many people still have inadequate metabolic control . Arguably, one of the biggest success stories in recent times has been the discovery and clinical realisation of exendin-4, a peptide originally isolated from the saliva of the venomous Gila monster (Heloderma suspectum) lizard. Exendin-4 has been chemically developed into exenatide (Byetta) and was approved by the FDA in 2005 .
In relation to this, a key focus of our laboratory for many years has been drug discovery, and our recent unpublished data has uncovered a novel peptides derived from tarantula spider venom. These peptides have been shown to be non-toxic to pancreatic beta-cells and stimulate insulin secretion. Furthermore, acute in vivo studies indicate that the novel peptides lower blood glucose concentrations in normal and diabetic rodents. Thus, spider venom derived peptides offer an exciting new anti-diabetes opportunity.
To extend these important observations and progress a possible novel therapeutic drug regimen for diabetes, we propose to:
*Elucidate the mechanism of action of novel venom derived peptides in pancreatic islet cells.
*Assess metabolic benefits of repeated daily dosing with novel peptides in preclinical models of obesity-diabetes.
*Determine the molecular mechanisms involved in the beneficial effects.
A wide range of methods are required for this study including peptide synthesis, HPLC purification of peptides, mass-spectrometry, in vitro insulin secretion studies, PCR and Western blot, longer term in vitro culturing, assessment of markers of proliferation and apoptosis, in vitro radio-receptor binding studies, animal studies in normal rodents as well as rodent models of obesity-diabetes, tissue gene expression studies, blood biochemistry assessments, DXA scanning and measurement of body fat, indirect calorimetry measurements, behavioural analysis and use of assays including ELISA and RIA technologies. This will provide excellent training in a wide variety of important research techniques.
Applicants should note that Bench fees of £3500.00 per annum are required.
1. Reach G, Pechtner V, Gentilella R, Corcos A, Ceriello A. Clinical inertia and its impact on treatment intensification in people with type 2 diabetes mellitus. Diabetes Metab. 2017: S1262-3636(17)30467-6.
2. Holst JJ. Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005. Diabetologia. 2006 Feb;49(2):253-60.
- Upper Second Class Honours (2:1) Degree from a UK institution (or overseas award deemed equivalent via UK NARIC)
- Sound understanding of subject area as evidenced by a comprehensive research proposal
If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.
- Experience using research methods or other approaches relevant to the subject domain
- A comprehensive and articulate personal statement
This is a self-funded PhD opportunity.
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