Cell-to-cell communication in Neurodegenerative Disorders

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 population (1).

Some 982,000 individuals are living with dementia in the UK; 13,625 in Northern Ireland (2). The estimated economic impact in the UK is £42.5 billion, with projections of £90 billion by 2040 (3). ALS has a worldwide prevalence of 3.37 per 100,000 (4) and incidence and prevalence are increasing in Northern Ireland, in line with other European countries (5). Given the significant personal and societal burden of neurodegenerative conditions, research to improve understanding and identify novel therapeutic targets is urgently needed.

Neurodegenerative diseases share numerous overlapping mechanisms, including protein aggregation, lysosome and mitochondrial dysfunction and alterations in lipid metabolism (6-7). Cell-cell communication also plays a key role and improved understanding of early cellular events are vital to identify drug targets with utility at an earlier stage in the disease process (8). Disrupted pathways vary depending on the specific cell types involved, which in turn affects cell behaviour. Depending on their mutational status, some cell types may have a neuroprotective role, while others are neurotoxic (9). Changes in cell-to-cell communication is known to impact neuronal degeneration across a range of neurodegenerative conditions (10-13) however the mechanisms are poorly understood.
The project will investigate cell-to-cell communication between neuronal and non-neuronal cells in neurodegenerative conditions and investigate therapeutic strategies to modulate cell-cell communication.

The project aims to:
1. Characterise neuronal and non-neuronal cells in different neurodegenerative conditions.
2. Analyse cell-to-cell communication between neurons, glia, astrocytes and myocytes in response to disease-associated protein aggregates and patient serum.
3. Investigate the impact of novel and established therapeutic strategies on cell-cell interactions to reduce neuronal degeneration.

Important Information: Applications for more than one PhD studentship are welcome, however if you apply for more than one PhD project within Medicine, 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.

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.

• Experience using research methods or other approaches relevant to the subject domain
• 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

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 record appropriate to career stage
• Experience of presentation of research findings

Equal Opportunities

The University is an equal opportunities employer and welcomes applicants from all sections of the community, particularly from those with disabilities.

Appointment will be made on merit.

Funding and eligibility

This project is funded by:

• Department for the Economy (DfE)
• Vice Chancellor's Research Scholarship (VCRS)

Our fully funded PhD scholarships will cover tuition fees and provide a maintenance allowance of £19,237 (tbc) per annum for three years* (subject to satisfactory academic performance).  A Research Training Support Grant (RTSG) of £900 per annum is also available.

These scholarships, funded via the Department for the Economy (DfE) and the Vice Chancellor’s Research Scholarships (VCRS), are open to applicants worldwide, regardless of residency or domicile.

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.

*Part time PhD scholarships may be available, based on 0.5 of the full time rate, and will require a six year registration period (individual project advertisements will note where part time options apply).

Due consideration should be given to financing your studies.