Summary

It is estimated that 415 million people worldwide suffer from diabetes which will rise to 642 million by 20401.  Ninety percent of cases are type 2 diabetes (T2D).  Treatment of secondary complications/comorbidities accounts for ~75% of the costs associated with T2D in the NHS2.  T2D is associated with hypertension (76%), arthritis (55%), coronary disease (28%), neuropathy (21%) and renal disease (18%)3; 47% of patients suffer 3 or more comorbidities.

Comorbid patients are routinely excluded from clinical trials, limiting our understanding of how treatments affect comorbidities4.  Comorbid patients commonly receive separate, fragmented treatment for each morbidity, with implications for cost and quality of care5.  It is not well understood (i) whether the association between comorbidities is driven by pathophysiological or lifestyle factors and (ii) whether one morbidity is causative of another or whether they share common causes.

There is a vast potential to grow our understanding of comorbidity and develop diagnostics, prognostics and interventions that can improve the quality of care for comorbid patients.  Here, we will focus on the pathophysiology of comorbidity and establish the relationship between T2D and its key comorbidities.

Aim 1 – Profile comorbidity in populations representative of the UK.

* Extract clinical and ‘omics data from UK Biobank (which does not cover Northern Ireland) and Ulster Genome Project, a large patient cohort study conducted by the Northern Ireland Centre for Stratified Medicine

* Prepare multidimensional analysis of comorbidity in T2D and identify significant morbidity combinations.

Aim 2 – Model the pathway biology of the key comorbidities.

* Use published literature, online databases and systems biology tools to map out the known molecular pathways that connect comorbidities.

* Develop and evaluate dynamic systems biology models of relevant molecular pathways.

Aim 3 – Identify genes/proteins/pathways associated with comorbidity development and targets contained therein.

* Undertake a gene set analysis of genome/proteome-wide association studies to determine SNPs/proteins/pathways statistically associated with development of significant morbidity combinations.

* Identify how loss-of-function/gain-of-function SNPs in genes or elevated/reduced protein/pathway activity drive comorbidity development.

* Identify SNPs in genes or binding sites in proteins that can be targeted to counter comorbidity development, therapeutically moderating comorbidity development.

The output of the project will be sets of predictive biomarkers of comorbidity and hypotheses of how these may be targeted therapeutically.  Biomarkers may be patentable and Ulster University (UU) has experience of securing Biomarker Intellectual Property.

The student will be placed at Ulster University (UU, 50% of time) and at Novo Nordisk (NN, 50%), including time at NN Research Centre Oxford (NNRCO) and NN’s headquarters near Copenhagen.  They will experience research in academic and industrial environments, with UU supporting data exploration and systems analysis/modelling (aims 1 and 2) and NNRCO supporting the analysis driving therapeutic target identification (aim 3). Comorbidity is an embryonic biomedical field and all aspects of the project will be novel and can lead to scientific publication.

[1] Ogurtsova K, et al. Diab Res Clin Pract (2017) 128, 40-50.

[2] Hex N, et al. Diabetic Med (2012) 29(7) 855-862.

[3] Kerr EA, et al. J General Internal Med (2007) 22(12), 1635-40.

[4] Gibson DS, et al. Exp Rev Precision Med Drug Dev (2017) 2(3) 147-156.

[5] Wallace E, et al. BMJ (2015) 305:H176.

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.

  • Demonstrable programming skills and mathematical ability.
  • Familiarity with biomedical science is desirable, but not essential.
  • Completion of Masters at a level equivalent to commendation or distinction at Ulster is desirable, but not essential.
  • A background in biomedical science, stratified/personalised medicine, bioinformatics, biomedical engineering, computer science, mathematics, physics or another quantitative science.

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

Funding

This project is funded by: DfE CAST award in collaboration with Novo Nordisk Research Centre Oxford

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £ 16,009 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.


Other information


The Doctoral College at Ulster University


Reviews

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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