"PhD Studentship: Non-coding RNAs as Biomarkers of Lewy Body Dementias and Related Traits - PhD (Alzheimer’s Society LBD DTN Funded)"

University of Exeter - Department of Clinical and Biomedical Sciences

Dementia with Lewy bodies (DLB) is a complex neurodegenerative disorder characterised by problems with memory, movement, sleep, and psychiatric symptoms. It is characterised by the accumulation of alpha-synuclein aggregates in neurons, forming Lewy bodies. A major challenge in the field is the lack of accurate and low-cost biomarkers for DLB, in particular in distinguishing it from Alzheimer’s disease (AD) and for informing on progression and prognosis. While AD and DLB share clinical features, they have distinct neuropathological hallmarks — yet many individuals show mixed pathology, making diagnosis challenging.

Small non-coding RNAs are a diverse class of regulatory molecules that influence gene expression at transcriptional and post-transcriptional levels. Recent studies, including from our group, have demonstrated robust alterations in small RNA expression profiles in brain and blood from individuals with AD and DLB. Despite these advances, it remains unclear whether such changes are disease-specific, reflect shared mechanisms, or capture distinct clinical phenotypes.

This project will investigate whether small non-coding RNAs can provide disease-specific signatures for DLB, and whether these could be developed into biomarkers. The student will sequence small RNAs from blood samples of healthy controls and individuals with DLB or AD. Using advanced bioinformatics, they will analyse small RNA expression across disease groups and sub-traits characteristic of DLB. Predictive modelling will test whether the most informative small RNAs can reliably distinguish between dementias in large independent datasets. To explore whether blood-based signatures reflect alterations in the brain, the project will also include analysis of post-mortem tissue datasets.

This research represents a multidisciplinary collaboration between the Universities of Exeter and Newcastle. Exeter has internationally recognised expertise in multi-omics, state-of-the-art sequencing, and computational pipelines. The Exeter team has led impactful studies exploring small RNAs in AD and DLB and will be the host institution. Newcastle is a world-leading centre for Lewy body research, offering access to well-characterised DLB and AD blood samples, alongside expert clinical insights. The supervisory team includes Professor Katie Lunnon, Professor John Paul-Taylor, and Dr Joshua Harvey, who together provide complementary expertise in dementia genomics, clinical research, and computational biology.

The findings will provide insights into peripheral signatures of DLB, assessing whether small RNAs can serve as reliable biomarkers. This project will advance understanding of disease mechanisms and lay the groundwork for biomarker development. It is suited to a candidate with a strong interest in dementia research, seeking to develop multi-disciplinary skills spanning laboratory and computational approaches.

The studentship will be awarded on the basis of academic merit. The studentship will cover Home tuition fees plus an annual tax-free stipend of at least £21,800 for 4 years full-time, or pro rata for part-time study.

Students who pay international tuition fees are eligible to apply. However, please note the following:

• The award covers only part of the international tuition fee, approximately £26,000.
• It does not include a stipend for living expenses.
• International applicants will need to cover additional costs, including:
  • Student visa fees
  • Immigration Health Surcharge
  • Relocation expenses associated with moving to the UK to undertake a PhD.

Applicants should ensure they have sufficient funds to meet these costs before applying.

Funding Comment

UK tuition fees and an annual tax-free stipend of at least £21,800 per year