PhD Study : ​Biomarkers Discovery for Early Detection of Diabetic Nephropathy using an untargeted Metabolomics approach

Summary

​Diabetes Mellitus (DM) is a systemic disease that affects millions of people worldwide. The prevalence of diabetes was estimated to be 2.8% in 2000 and projections estimate it will rise to 4.4% in 2030. This increase is particularly relevant in urbanized areas where inactive lifestyles contribute to diabetes development Diabetic Nephropathy (DN) is a microvascular complication arising most commonly from type 1 DM, but can also develop in type 2 DM sufferers. It is currently the leading cause of end-stage renal disease (ESRD) which requires the use of dialysis and ultimately renal transplantation.    A moderate increase in the amount of albumin in the urine, termed microalbuminuria, is routinely measured in DM patients and is the primary method of indication of DN development risk. Microalbuminuria can lead to macroalbuminuria (an albuminuria excretion rate (AER) of >300 mg/d or 200 μg/min) which is a feature of DN along with other complications such as a reduction in glomerular filtration rate and hypertension.

The rate of progression of microalbuminuria to macroalbuminuria is believed to be 15-30% over a 5 to 10 year period or as high as 45% in patients with less than 15 years of diabetes duration. This can occur despite strict management of hyperglycemia. However, this diagnostic method has limitations in that not all patients who have microalbuminuria develop DN. In addition, there are several preceding biomarkers, such as KIM-1, NGAL, Cystatin C, for example, suggestive of kidney damage which suggests that kidney damage may have already occurred at this stage. Consequently, the use of this diagnostic method may not be an effective diagnostic tool for DN.The focus is now on the use of novel biomarkers for early detection of DN and a better indication of its progression in patients. It is important that DN is diagnosed and intervention carried out as soon as possible to prevent further kidney degeneration, the development of ESRD and other complications that may arise as a consequence.

The aim of this study is therefore to identify new biomarkers that can be applied in early stage diagnosis of DN.

Objectives:

Objective 1:To develop extraction protocols and Liquid chromatography-Mass Spectrometry platforms for untargeted metabolomics in plasma and urine biomatrices.

Objective 2:To identify unknown metabolites using the developed platform in Objective 1 in stratified participant samples (plasma and urine)

Objective 3: to identify the best early predictors of DN from metabolites measured in Objective 2.

Study design and methods

Study design: this study is a one-point observation study where health and lifestyle data,and blood/urine samples were collected from; 1) Non-DM, 2) T2DM, 3) DM-DN patients, and will be analysed for early biomarkers of DN. All relevant ethical approvals are in place and samples are currently stored in -80C freezers at CMB. Samples from Stratified cohorts Group 1: Non-DM individuals Group 2: T2DM patients Group 3: DM patients with diagnosed DN. ​

Please note: Applications for more than one PhD studentships are welcome, however if you apply for more than one PhD project within Biomedical Sciences, your first application on the system will be deemed your first-choice preference and further applications will be ordered based on the sequential time of submission. If you are successfully shortlisted, you will be interviewed only on your first-choice application and ranked accordingly. Those ranked highest will be offered a PhD studentship. In the situation where you are ranked highly and your first-choice project is already allocated to someone who was ranked higher than you, you may be offered your 2nd or 3rd choice project depending on the availability of this project.

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.

• Sound understanding of subject area as evidenced by a comprehensive research proposal
• Clearly defined research proposal detailing background, research questions, aims and methodology

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.

• Completion of Masters at a level equivalent to commendation or distinction at Ulster
• Experience using research methods or other approaches relevant to the subject domain
• Sound understanding of subject area as evidenced by a comprehensive research proposal
• Work experience relevant to the proposed project
• Publications record appropriate to career stage
• 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

Funding and eligibility

The University offers the following levels of support:

Vice Chancellors Research Studentship (VCRS)

The following scholarship options are available to applicants worldwide:

• Full Award: (full-time tuition fees + £19,000 (tbc))
• Part Award: (full-time tuition fees + £9,500)
• Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

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.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

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