Summary

The gastrointestinal tract (GIT) harbours numerous important peptide hormones that regulate normal physiology. One such GIT-derived hormone, known as xenin, is secreted from intestinal K-cells in response to feeding. Interestingly, the well-characterised incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), is also released postprandially from K-cells, and there is evidence that the biological actions of xenin and GIP are complementary.

Therefore, the present studies are designed to delineate the full physiological role of xenin, with observations likely to have significant therapeutic relevance. Initially, liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS) will be used to quantify time- and nutrient-dependent changes in xenin secretory profiles using suitable GIT cell lines and in vivo in mice.

Previous research at Ulster has revealed various xenin metabolites are present in blood, and each will be quantified. In addition, receptor interactions (SGLTs, FFAs, GLUTs etc.) and related signalling pathways activated during xenin release will be analysed. Immunohistochemical techniques and scanning electron microscopy will be employed to uncover the exact location of xenin secretory granules within GIT cells. Further published evidence from Ulster reveals local pancreatic synthesis and secretion of xenin.

To validate this, we will determine the expression of COPA (xenin precursor), the proteolytic cleavage enzyme cathepsin E, and then concentrations of xenin peptides in pancreatic beta-cell lines and isolated mouse islets under normal and stressed (high or low glucose/lipid) conditions. Further to this, the biological actions of xenin, and related fragment peptides, will be investigated at pancreatic and extra-pancreatic sites. In brief, effects on pancreatic beta-cell insulin secretion, proliferation and apoptosis will be studied, alongside gene and protein expression of key beta-cell markers involved in insulin secretion and beta-cell survival.

Similar investigations on glucagon secretion and alpha-cell signalling will also be conducted. Since GIP has well characterised positive effects on bone, the impact of xenin on bone physiology will be examined. Effects of xenin peptides on in vitro osteoblast proliferation, and secretion of TGF-beta, IGF-I and FGF-2, as well as alkaline phosphatase activity, will be assessed. Osteoclast cultures will be used to determine effects of xenin on osteoclast formation. Furthermore, 3T3-L1 adipocytes will be utilised to uncover the role of xenin and related peptides in lipid metabolism.

Studies will involve measurement of key processes in lipid synthesis as well as glucose uptake. Xenin effects on the modulation of adipogenic-specific genes/proteins during adipocyte differentiation will also be studied. Finally, the action of xenin on muscle and liver will be investigated, including glucose transport in L6 myocytes and effects on primary murine hepatocyte-viability, steatosis, ER stress and autophagy.

Together, this PhD project will provide excellent training in a wide range of state-of-the-art research techniques.

We are seeking an applicant with good practical laboratory, computer and communication skills and enthusiasm and commitment to work diligently on all aspects of the research project. A background in biomedical sciences, pharmacology or a related subject would be desirable. This is one of three top priority projects for Ulster’s Diabetes Research Group. Informal enquiries to Dr Irwin (n.irwin@ulster.ac.uk) are welcomed.


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.
  • Sound understanding of subject area as evidenced by a comprehensive research proposal

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.

  • First Class Honours (1st) Degree
  • Masters at 65%
  • Research project completion within taught Masters degree or MRES
  • Practice-based research experience and/or dissemination
  • Experience using research methods or other approaches relevant to the subject domain
  • Work experience relevant to the proposed project
  • Publications - peer-reviewed
  • Experience of presentation of research findings
  • A comprehensive and articulate personal statement
  • Relevant professional qualification and/or a Degree in a Health or Health related area

    The University offers the following awards to support PhD study and applications are invited from UK, EU and overseas for the following levels of support:

    Vice Chancellors Research Studentship (VCRS)

    Full award (full-time PhD fees + DfE level of maintenance grant + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees and provide the recipient with £15,000 maintenance grant 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.

    Vice-Chancellor’s Research Bursary (VCRB)

    Part award (full-time PhD fees + 50% DfE level of maintenance grant + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees and provide the recipient with £7,500 maintenance grant 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.

    Vice-Chancellor’s Research Fees Bursary (VCRFB)

    Fees only award (PhD fees + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees 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.

    Department for the Economy (DFE)

    The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £15,285 per annum for three years. EU applicants will only be eligible for the fee’s component of the studentship (no maintenance award is provided). For Non-EU nationals the candidate must be "settled" in the UK. 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.

    Due consideration should be given to financing your studies; for further information on cost of living etc. please refer to: www.ulster.ac.uk/doctoralcollege/postgraduate-research/fees-and-funding/financing-your-studies



The Doctoral College at Ulster University


Reviews

Profile picture of Kamin Hau

Kamin Hau - PhD in Biomedical Sciences


Profile picture of Kieran O'Donnell

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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Profile picture of Michelle Clements Clements

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


Profile picture of Poonam Singh Nigam

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


Profile picture of William Crowe

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 Ryan Kelsey

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


Profile picture of Ahmed Abuelhana

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


Profile picture of Ryan Lafferty

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