Summary

Adipose tissue is now recognised as much more than an excess energy storage depot but is in fact a metabolically active organ [1].  Several adipokines signal to other tissues to help coordinate physiological processes including energy homeostasis [1].  Imbalanced adipokine production is thought to contribute to the pathogenesis of obesity related Type 2 diabetes and cardiovascular disease (CVD) complications [2]. Adipokines upregulated in obesity, including adiponectin and apelin, can exert anti-inflammatory and cardio-protective effects [3], whereas others impair cardiovascular function [3].

This project will focus on apelin, which is known to exist in various isoforms (processed from a larger apelin-77 precursor), including apelin-36, apelin-17, (pGlu)apelin-13 and apelin-13. Apelin-13 has multiple biological actions mediated through its cognate APJ receptor. There is growing interest in the role of apelin in metabolic diseases including T2DM, obesity and CVD [4,5]. A recent meta-analysis showed low circulating apelin concentrations are associated with a higher risk of hypertension [6].  Coronary heart disease subjects were reported to have lower apelin concentrations compared to healthy controls [7,8].  Despite this, relatively little is known about the role of apelin in the pathophysiology of obesity and diabetes.  Some studies show that circulating apelin concentrations are elevated in T2DM and obesity, but others suggest that it is lower [9].

Experimental Design:

The current research study will improve our understanding of the pathophysiology of apelin, while assessing its utility as a disease biomarker in stratified human clinical samples by quantifying various apelin isoforms in plasma samples under a variety of conditions. A HPLC method with MS verification will be used to examine peptide recovery from mouse plasma samples.

*Examining the stability and half-life of natural isoforms of apelin (e.g. apelin-36, (pGlu)apelin-13 and apelin-13) in mouse plasma in vitro using a HPLC based assay with peptide identification by mass spectrometry.

*To determine the recovery of apelin isoforms following sample spiking to determine assay recovery, variability and sensitivity.

*Measurement of apelin isoforms in human subjects at risk of diabetes (e.g. pre-diabetes and obese populations BMI>25 kg/m2) or during the time course of an OGTT (e.g. DexLife Study).

Methods:

A reversed phase HPLC method will be used to examine peptide recovery from mouse plasma samples following spiking with synthetic forms of the naturally occurring peptides. An ELISA assay apelin-13 will be used to measure apelin in human plasma/serum samples.  LC-MS and MALDI-TOF mass spectrometry techniques will be developed to look at the quantification of various isoforms using spiked plasma samples.

Skills required of applicant:

The applicant should ideally have good practical laboratory, computer and communication skills and show enthusiasm and commitment to work diligently on all aspects the research project. A background in biomedical sciences, biochemistry, pharmacology or a related subject would be desirable.

References:

[1]    Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 2005;115:911-920.

[2]    Shibata R, et al. The role of adipokines in cardiovascular disease. J Cardiol 2017;70(4):329-334.

[3]    Smekal A, et al. Adipokines and cardiovascular disease: A comprehensive review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2017;161:31– 40.

[4]    Cudnoch Jedrzejewska A, et al. The role of apelin in pathogenesis of Cardiovascular diseases and metabolic disorders].  
Kardiol Pol 2011;69 Suppl 3:89 –93.

[5]    Castan-Laurell I, et al. Apelin, diabetes, and obesity. Endocrine 2011;40:1–9.

[6]    Xie H, et al. Lowered circulating apelin is significantly associated with an increased risk for hypertension: a meta-analysis. Clin Exp Hypertens 2017;39:435– 440.

[7]   Chen T, et al. Association of apelin and apelin receptor with the risk of coronary artery disease:  A meta-analysis of observational studies. Oncotarget 2015;8(34).

[8]   Zhang BH, et al. Cardioprotective effects of adipokine apelin on myocardial infarction. Heart Vessels 2014;29:679 – 689.

[9]   Castan-Laurell I, et al. Apelin, a novel adipokine over-produced in obesity: Friend or foe? Mol Cell Endocrinol 2005;245:7–9

[10]  O'Harte FPM, et al. Acylated apelin-13 amide analogues exhibit enzyme resistance and prolonged insulin releasing, glucose lowering and anorexic properties. Biochem Pharmacol 2017;15;146:165-17


Essential criteria

  • To hold, or expect to achieve by 15 August, an Upper Second Class Honours (2:1) Degree or equivalent from a UK institution (or overseas award deemed to be equivalent via UK NARIC) in a related or cognate field.


The Doctoral College at Ulster University


Reviews

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My experience has been great and the people that I have worked with have been amazing

Kieran O'Donnell - 3D printing of biological cells for tissue engineering applications

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Kamin Hau - PhD in Biomedical Sciences


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Completing the MRes provided me with a lot of different skills, particularly in research methods and lab skills.

Michelle Clements Clements - MRes - Life and Health Sciences

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Profile picture of Sarah Craig

I completed my undergraduate studies at Ulster University, where I graduated in 2017 with first class honours in Biomedical Science with a Diploma in Professional Practice . I joined the Diabetes Research group as a PhD researcher in September 2017 and completed my PhD studies in June 2020.I am proud to say I not only completed my PhD studies within 3 years, but also became the World Champion (with a perfect score!) in Irish Dance during my PhD studies. My favourite memory was the opportunity to present my PhD work at the EASD conference in 2019. If I could speak to myself at the start of my PhD, the best piece of advice I would give myself would be to enjoy every single minute as the time flies in. I really would do another PhD!

Sarah Craig - PhD in Biomedical Sciences


Profile picture of Natalie Klempel

I completed my undergraduate studies in America at Texas Woman’s University where I majored in Kinesiology. I then moved to Scotland to successfully complete my Masters with Merit in Human Anatomy at the University of Dundee.My proudest moment was when I passed my viva! My favourite memory was …the dissections. I’ll never forget the friends I made and the good times we had together. I couldn’t have got through this without the support of my family, friends, lab colleagues, supervisors, and my boyfriend. If I could speak to myself at the start of my PhD, the best piece of advice I would give myself would be to write up after every experiment, keep a lot of back up copies of the work, and to enjoy the experience.

Natalie Klempel - PhD in Biomedical Sciences


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Throughout my PhD I’ve been provided with continuous support and guidance by my supervisors and the staff at the University.I’ve also received many opportunities to further enhance my professional development in the form of teaching experience and presenting my work at conferences which will aid in my pursuit of a career in academia or industry.

William Crowe


Profile picture of Charlotte Zoe Angel

I studied Medical Neuroscience at the University of Sussex followed by a year working in Industry and then a Master's in Genetics at the University of Lyon in France, before coming to Ulster University for my PhD in Biomedical Sciences.I want to thank my fantastic supervisors Declan McKenna and Colum Walsh for teaching me so much and for being so supportive. I had a brilliant PhD experience, made all the better by my lovely supervisors, office-buddies, tearoom-buddies, and other friends. I also want to thank the amazing staff at the Coleraine campus gym for being so much fun and for giving me my love of fitness. I am so glad that I decided to join in the first year - it was really the thing that kept me sane during the stressful periods and I so enjoyed being part of that community. My best wishes to the rest of my cohort and good luck for the future.

Charlotte Zoe Angel - PhD in Biomedical Sciences


Profile picture of Prawej Ansari

I am originally from Nepal, having received my undergraduate and master's degree from Bangladesh. During my Master's degree, I chose area of diabetes research and then I was offered a PhD in the School of Biomedical Sciences on Diabetes Research. Currently, I'm working as a Scientist at Randox Laboratories Ltd. Thus, I would like to thank my supervisors, without them I wouldn't be in this position today.My proudest moment was when I presented my research outcomes to an international symposium. My favorite memory was the love of university staff and colleagues during my PhD tenure. I’ll never forget my supervisors, and especially Professor Peter Flatt, who has guided me in each step of my PhD life. I couldn’t have got through this without Professor Peter Flatt and Dr Yasser Abdel-Wahab and the University’s staff support.If I could speak to myself at the start of my PhD, the best piece of advice I would give myself would be after all the hard work, you will receive a

Prawej Ansari - PhD in Biomedical Sciences


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I joined Ulster university in Jan 1990 after completing Postdoctoral research in Germany (1986-88) and PhD in India (1985). DSc degree in Applied Microbial-Biotechnology has been awarded after the evaluation of my thesis based on Research, Publication & related activities, completed as a research-active academic member of staff (1990-2019). DSc thesis summarised my scientific outputs and contributions (183 research papers, 3 biotechnology reference-books, 43 research-informed book-chapters, 26 research-informed review-articles, 90 conference-abstracts,1 European Patent and 2 Technology-transfers; Supervision of National & International researchers-18 Postdoctoral/Exchange and 12 PhD; and affiliations as Examiner of 58 PhD researchers globally, and Fellow & Member of nine scientific & academic societies.My message to all researchers is that "Chase your Aspirations and Never Give up". I couldn’t have got through my long academic & Professional journey without

Poonam Singh Nigam - DSc in Biomedical Sciences


Profile picture of Karl Smith

I started my PhD after I completed my undergraduate in Biology at Ulster University in 2016, with a dissertation project that focused on genetic variations in bacterial species. I continued using some of these techniques in my doctoral research, which primarily involved the investigation and development of mass spectrometry imaging in vitamin D treated prostate cancer, looking at the metabolic and genetic variations upon treatment. I worked with international collaborators at the University of Edinburgh and Maastricht University, where I got to learn and develop mass spectrometry techniques that have not previously been carried out in Northern Ireland. I now work as a postdoctoral researcher at the National High Magnetic Field Laboratory at Florida State University in Tallahassee, Florida, where I am helping to develop and implement a mass spectrometry imaging facility for users across the world with the super powerful 21T FT-ICR mass spectrometer.A PhD is a demanding process but when

Karl Smith - PhD in Biomedical Sciences


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I graduated Ulster University in 2016 with a degree in Biomedical Science with DPP (Pathology). I was then offered a PhD studentship with Dr Catriona Kelly and Professor Neville McClenaghan at CTRIC which I started in September 2016. My PhD explored the pathophysiology of Cystic Fibrosis-Related Diabetes, the most common co-morbidity associated with Cystic Fibrosis.My proudest moment was undoubtedly passing my Viva (via Skype!), but I was also proud to be given the opportunity to present my work at the UK Cystic Fibrosis Trust Conference in 2018. Through this conference, I was able to meet with people with CF and the challenges they face which was important reminder that the research I was doing mattered. I couldn't have got through this without the unwavering support of my family, who were always there for me in the good times and the bad. I am also extremely grateful for the support and mentorship of my supervisors Dr Catriona Kelly, Professor Neville McClenaghan and Dr Dawood Khan

Ryan Kelsey - PhD in Biomedical Sciences


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My proudest moment was when I knew the possibility of the full transfer of my PhD project to Ulster University, the University which I loved and started my first steps towards my PhD in, and also being a PhD graduate from one of the highly reputable universities such as Ulster is a big thing which I should always be proud of. I think there is no that word that can ever express my deepest thanks and sincere appreciation to my supervisor Professor Kathryn Burnett for her ideal supervision, valuable guidance, encouragement, generous help and ultimate support throughout my PhD project. I have been really lucky to have her as a supervisor. Also my deepest gratitude to Mr Linden Ashfield, Principal Clinical Pharmacist, Antrim Area Hospital (NHSCT) for his help and endless support throughout the whole research project. Also, I could not have got through this without the support of my beloved family (my father ”Sayed”, my mother ”Gamila”, my wife “Nermeen”

Ahmed Abuelhana - PhD in Biomedical Sciences


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I graduated from Queen's University Belfast with a Master's in pharmacy in 2014 and subsequently began working as a community pharmacist in the Greater Belfast area. My career began to take an unusual turn when I got involved with a small startup company who developed a novel blood glucose monitor for diabetic patients. From here, my interest in diabetes was piqued and I applied for a PhD project (somewhat optimistically!) in the Diabetes Research Group at Ulster. Nearly four years later, I'm still there working as a postdoctoral researcher. Not bad considering I never thought I had a chance of getting a PhD spot!My time within the DRG has been, and still is, fantastic. I've made life-long friends (and surprisingly few enemies!) who have been patient, helpful and a joy to collaborate with. I couldn't have got through it without them (you know who you are). Likewise, the guidance from my supervisors, Prof. Peter Flatt and Dr. Nigel Irwin, has been invaluable. I'm probably most proud of

Ryan Lafferty - PhD in Biomedical Sciences