PhD Opportunity – EASTBIO: Exploring Dementia’s Umbrella: AI-Enhanced Stratification of Disease Subtypes
Project Title:
EASTBIO: Exploring Dementia’s Umbrella: AI-Enhanced Stratification of Disease Subtypes
Supervisor(s):
Principal Supervisor: Dr Marco Fernandes (School of Medicine), [email protected].
Co-supervisors: Dr Ilary Allodi (School of Psychology and Neuroscience), [email protected] and Professor Peter Donnelly (School of Medicine), [email protected].
Deadline:
Friday 17 January 2025
Project Description:
Dementia, an umbrella term encompassing a wide range of brain diseases, sees 7.2 million new cases globally each year. While some subtypes are more common and easier to differentiate, conditions such as Alzheimer’s disease (AD), Frontotemporal Dementia (FTD), and Motor Neurone Disease (MND) present challenges due to their overlapping clinical and pathological features. FTD is marked by degeneration of the frontal and temporal lobes, resulting in changes in personality, behaviour, and language, while MND involves degeneration of motor neurones, leading to muscle weakness and atrophy. Some patients exhibit symptoms of both conditions, suggesting a spectrum of phenotypes linked by frontotemporal lobar degeneration. At present, there is no cure for either disorder, and treatment options are limited to symptom management and supportive care.
Recent advances in high-throughput technologies now allow access to rich multimodal datasets from longitudinal studies, including whole-genome sequencing, RNA sequencing, proteomics, metabolomics, and combined approaches — spatial transcriptomics. These datasets present an unprecedented opportunity to investigate the molecular complexities underlying FTD and MND, however their high-dimensional nature poses significant analytical challenges. Emerging artificial intelligence (AI) tools, such as deep learning and variational autoencoders, are transforming this field by uncovering latent molecular phenotypes and identifying patterns that traditional methods might overlook.
This PhD project aims to harness AI to explore the molecular landscape of FTD and MND, with a focus on two interconnected objectives:
(A) AI-Based Patient Stratification: Develop and apply AI models to cluster patients using multimodal data, revealing distinct molecular subtypes of FTD/MND. Techniques such as variational autoencoders will be employed to reduce data dimensionality for clustering, with validation conducted against clinical outcomes and cognitive profiles. This stratification aims to inform personalised therapeutic strategies and improve prognostic models.
(B) Pathway Activity Analysis: Investigate the roles of the endosomal pathway and the immune system by comparing pathway activities across patient subgroups. Dysregulation of the endosomal–lysosomal pathway, involving key mutations such as C9orf72 and GRN, has been implicated in disease progression. Pathway enrichment analyses using established ontology databases (e.g., GO, KEGG, Reactome) will identify critical biological processes driving these diseases. Integrating these findings with molecular phenotypes will help uncover potential therapeutic targets.
The interdisciplinary supervisory team, comprising Dr Fernandes (Bioinformatics), Dr Allodi (Neuroscience), and Prof Donnelly (Public Health), will provide comprehensive training in state-of-the-art techniques for modelling multimodal data, investigating pathway-level mechanisms in FTD/MND, and exploring the potential translation of findings into clinical care policies.
Funding Details:
This 4-year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership.
This opportunity is open to UK and International students and provides funding to cover stipend at UKRI standard rate and UK level tuition fees. The University of St Andrews will cover the Home-International fee difference.
How to Apply:
Application instructions can be found on the EASTBIO website – https://biology.ed.ac.uk/eastbio/how-to-apply.
1) Download and complete the Equality, Diversity and Inclusion survey.
2) Download and complete the EASTBIO Application Form.
3) Submit an application to St Andrews University through the Online Application Portal.
Your online application must include the following documents:
- Completed EASTBIO application form.
- 2 References (to be completed on the EASTBIO Reference Form, also found on the EASTBIO website).
- Academic Qualifications.
- English Language Qualification (if applicable).
Unfortunately, due to workload constraints, we cannot consider incomplete applications. Please make sure your application is complete by 17th January 2025.
Contact:
Queries on the project can be directed to the project supervisor.
Queries on the application process can be directed to Rachel Horn at [email protected].
UKRI eligibility guidance: Terms and Conditions: View Website International/EU: View Website.