Background: Marine sources, such as protein hydrolysates from fish and seaweed (e.g. Palmaria palmata), represent good sustainable raw material sources for the mining of bioactive peptides. Such peptides have potential for improving metabolic control in Type 2 diabetes (T2DM) and obesity [1]. This project will assess the ability of specific marine protein-derived peptides (produced from enzymatic digestion), for their potential in improving glycaemic control and satiety in diabetes.
Previous studies have indicated that seaweed derived peptides and fish protein hydrolysates, elicit marked insulin releasing activity in BRIN-BD11 cells, as well as DPP-4 enzyme inhibitory activities [2-4]. Initial screening of crude hydrolysates and their HPLC purified components will be tested for insulin releasing ability in cultured pancreatic BRIN-BD11 cells [5]. Selected marine peptides will be identified by mass spectrometry and screened for their insulinotropic activity in cultured pancreatic BRIN-BD11 cells, inhibition of DPP-4 enzyme activity and stimulation of GLP-1 secretion from GLUTag cells.
Peptides (n=4-8) showing the highest relevant bioactivities will be further assessed in vivo in normal adult C57Bl/6 male mice. Acute glucose tolerance, dose-dependent actions and pharmacokinetics will be examined in these mice. Further studies on satiety and food intake will be performed in diet restricted mice trained to eat for 3 h per day [6]. Structure-function studies will be undertaken using selected peptide analogues and their potency will be tested in acute in vitro studies as indicated above.
A small number (n=2-4 peptides) of marine peptides and/or selected analogues thereof will be tested in a chronic setting with high fat fed (45% fat), diet induced obese (DIO) diabetic mice. This proposal aim is to test the hypothesis that marine peptides have potential in glycaemic management and satiety control.
Methodology: Characterization of marine peptides by RP-HPLC separation and mass spectrometry (MS) will help identify selective candidate bioactive peptides, which will then be produced synthetically. A range of in vitro screening bioassays, including assessment of DPP-4 enzyme activity, insulin and GLP-1 secretion will be performed.
Further, in vivo testing as described above, will be undertaken to help identify lead candidate peptides. Chronic peptide administration of lead candidate peptides/analogues in DIO mice will be followed directly by indirect calorimetry, energy expenditure and locomotor activity studies, using the CLAMS small animal apparatus and DEXA analysis.
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.
References:
[1] Sharkey S, et al.A Narrative Review of the Anti-Hyperglycemic and Satiating Effects of Fish Protein Hydrolysates and Their Bioactive Peptides. Molecular Nutrition and Food Research. 2020:64(21), 2000403.
[2] McLaughlin CM, et al. Twice daily oral administration of Palmaria palmata protein hydrolysate reduces food intake in streptozotocin induced diabetic mice, improving glycaemic control and lipid profiles. Journal of Functional Foods. 2020:73, 104101.
[3] Pathsarathy V, et al. Boarfish (Capros aper) protein hydrolysate has potent insulinotropic and GLP-1 secretory activity in vitro and acute glucose lowering effects in mice. International Journal of Food Science and Technology. 2019:54(1), 271-281.
[4] Harnedy PA, et al. Atlantic salmon (Salmo salar) co-product-derived protein hydrolysates: A source of antidiabetic peptides. Food Research International. 2018:106, 598-606.
[5] McClenaghan NH, et al. Characterization of a novel glucose-responsive insulin-secreting cell line, BRIN-BD11, produced by electrofusion. Diabetes. 1996:45(8), 1132-1140.
[6] O'Harte FPM, et al. Apelin-13 analogues show potent in vitro and in vivo insulinotropic and glucose lowering actions. Peptides. 2018:100, 219-228.
Submission deadline
Wednesday 1 September 2021
12:00AM
Interview Date
To Be Confirmed
Preferred student start date
To Be Confirmed
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