PhD Study : Extraction, characterization and exploitation of marine derived bioactive peptides for enhancing health

Summary

Background:

Low-value pelagic fish (e.g. Blue whiting) provide an abundant source of underutilized and potentially high-value functional proteins and peptides [1]. This project will investigate the potential of biofunctional peptides derived from the enzymatic digestion of marine proteins, to enhance satiety and reduce food intake. Fish protein hydrolysates (FPH) will be screened using cellular bioassays associated with markers of appetite control. Lead candidates that reduce food intake will be assessed in acute and chronic mouse studies. Lead hydrolysates will be formulated into food products and sensory studies performed. LC-MS analysis will help characterise the peptide profile and identify the bioactive peptides present in hydrolysates. This project will help validate the strategic use of fish protein hydrolysates for health promotion and disease prevention.

Objective:

The main objective will be to characterise biofunctional peptide ingredients from fish protein hydrolysates with appetite modulating activities.

Study 1: Fish protein hydrolysates (FPH), will be tested in pancreatic BRIN-BD11 cells [2], measuring insulin secretion by RIA, and cytotoxicity by MTT and LDH assays. Bioactive peptides from FPH affecting appetite control hormones will be screened and identified using RP-HPLC and LC-MS.  Identified synthetic peptides will be tested on cellular appetite hormone secretion and food intake in mice.

Study 2: Adult male NIH Swiss mice (4 groups of n=8) will be conditioned to eat for 3 h per day (10.00 h to 13.00 h).  Food intake will be assessed at 30 min intervals up to 180 min, following oral gavage with selected FPH or synthetic peptides (oral/i.p. injection) [3].

Study 3: Following oral glucose challenge with or without hydrolysate (50 and 200 mg/kg) blood glucose, plasma PYY, ghrelin, total GLP-1, CCK-8, glucagon and insulin concentrations, and DPP-4 enzyme activity will be assessed from tail blood at regular intervals (0-120 min). A delayed oral glucose tolerance test (OGTT) will be undertaken (2, 4, 8 and 12 h) to obtain information on the pharmacokinetics and duration of action of hydrolysates [4] to determine the frequency of dosing for Task 4.

Study 4: Chronic effects of FPH will be tested for 28 days in a high-fat fed mouse model of diet-induced obesity (DIO) [5].  Food intake, non-fasting blood glucose, plasma insulin, plasma GLP-1, PYY, CCK-8, ghrelin, DPP-4 activity and body weight will be determined at regular intervals up to 28 days.  An OGTT and insulin sensitivity test will be performed after 28 days. The CLAMS apparatus will determine energy intake and expenditure [6]. The PIXImus DEXA scanner will measure body composition and bone density [7].

These studies will inform development of appetite modulating hydrolysates and their incorporation into food products, including ongoing sensory analysis with collaborators in Galway and Limerick.

References:

[1] Harnedy et al., Journal of Functional Foods 2018;40:137-145

[2] McClenaghan NH, et al., Diabetes, 1996;45:1132-1140.

[3] O'Harte FPM, et al., Diabetes, 1998;47:1619-1624.

[4] Lynch AM, et al., European Journal of Pharmacology, 2014;743:69-78.

[5] O'Harte FPM, et al., Molecular and Cellular Endocrinology, 2013;381:26-34.

[6] Gault VA, et al., Journal of Endocrinology, 2011;208:265-271.

[7] Pathak V, et al., Molecular and Cellular Endocrinology, 2015;401:120-129.

Essential criteria

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.

Desirable Criteria

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
• Experience of presentation of research findings

Funding and eligibility

The University offers the following levels of support:

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

• Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
• Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
• Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
• Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living

DfE matched funding