PhD Study : The potential of circulating diagnostic and prognostic biomarkers in neurodegenerative and neuromuscular diseases

Summary

Age-associated neurodegenerative diseases, including dementias, such as Alzheimer’s disease (AD) and Frontotemporal dementia (FTD), and clinically overlapping conditions such as Parkinson’s Disease (PD) and Amyotrophic Lateral Sclerosis (ALS), are increasing, in line with the aging worldwide population1. All are associated with significant diagnostic delays. When assessed at specialist dementia clinics, 25-30% of patients with AD are misdiagnosed, with similar, or worse, diagnostic outcomes for FTD or dementia with Lewy bodies (DLB)2-4. Misdiagnosis rates in primary care are higher still5. The poverty of adequate diagnostic tools for ALS6 and PD7 are underlined by diagnostic delays of ~10-16 months, impacting access to timely treatment and support.

There remains a critical unmet need for objective blood-based biomarkers for differential diagnosis of these conditions. Neurodegenerative diseases share numerous overlapping mechanisms, including protein aggregation, autosomal-lysosome and mitochondrial dysfunction and alterations in lipid metabolism8,9. Extracellular vesicles (EVs) contribute to many physiological processes in the central nervous system (CNS) including neuroprotection from oxidative stress10 and their cargoes reflect the status of their cell of origin11. However, EVs are also implicated in neurodegeneration, particularly in the context of spreading toxic protein aggregrates12. As EVs can cross the blood-brain barrier and be detected in the bloodstream, they offer a unique advantage in evaluation of dysregulation in the CNS13.

The project will investigate the content of EVs, including lipids, as potential diagnostic, prognostic and predictive biomarkers across several neurodegenerative diseases.

The project aims to:

1. Assess and validate circulating biomarkers for diagnosis, prognosis and prediction of clinically overlapping neurodegenerative conditions.
2. Conduct in silico exploration of functional pathways via genomics and other data types, using in-house and publicly available datasets, focusing on modelling of EV- and lipid-related pathways.
3. Cross-reference biomarker candidates to in silico findings in order to provide mechanistic understanding of disease profiles and suggest new biomarker/therapeutic leads.

AccessNI clearance required

Please note, the successful candidate will be required to obtain AccessNI clearance prior to registration due to the nature of the 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
• A comprehensive and articulate personal statement
• Research proposal of 1500 words detailing aims, objectives, milestones and methodology of the project
• A demonstrable interest in the research area associated with the studentship

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 70%
• Research project completion within taught Masters degree or MRES
• Experience using research methods or other approaches relevant to the subject domain
• Publications - peer-reviewed
• Publications record appropriate to career stage
• Experience of presentation of research findings

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