About the Project
White matter consists of long-range, myelinated axonal pathways that coordinate information flow across brain networks. In ageing, reduced cerebral perfusion and vascular dysfunction render white matter tracts particularly vulnerable. Despite the prevalence of white matter abnormalities and their relevance to cognitive decline, the mechanisms underlying age-related white matter vulnerability and resilience remain incompletely defined. Emerging evidence, including our studies, suggests that…
age-related reductions in cerebral blood flow alter oligodendrocyte biology and impair myelin homeostasis. This PhD project will determine how chronic cerebral hypoperfusion alters oligodendrocytes and myelin, and how these changes relate to cognitive function during brain ageing.
We have established a well-characterised mouse model of chronic cerebral hypoperfusion that recapitulates age-associated reductions in blood flow and produces progressive white matter damage with measurable cognitive consequences. Our preliminary single-cell RNA-sequencing studies identify early transcriptional changes in oligodendrocytes following hypoperfusion, providing an opportunity to define mechanisms linking reduced cerebral blood flow to oligodendrocyte and myelin dysfunction.
The student will use single-cell and spatial transcriptomic approaches to determine how oligodendrocyte populations change during the emergence and progression of white matter abnormalities, and how these changes relate to myelin damage. As endothelial cells are also altered by hypoperfusion, bioinformatic analyses will identify candidate signalling pathways linking vascular dysfunction to altered oligodendrocyte biology.
Following hypoperfusion, we have identified neuroinflammation using TSPO PET with [18F]-LW223 and white matter microstructural alterations using diffusion MRI. Longitudinal PET/MRI and behavioural testing will relate molecular and cellular changes to evolving white matter abnormalities and cognitive function. Analysis of post-mortem white matter will determine whether comparable oligodendrocyte alterations occur during human brain ageing. By defining how declining cerebral blood flow influences oligodendrocyte and myelin biology, the project will use interdisciplinary approaches to identify mechanisms contributing to white matter vulnerability and cognitive decline during brain ageing.
This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP). Detailed guidance on the application process, and the EASTBIO Application and Reference Forms can be found at How to Apply | Biology.
Please send your completed EASTBIO Application Form along with a copy of your academic transcripts (as a pdf) to INCR.PostgraduateRecruitment@ed.ac.uk. You should also contact your referees and ask them to submit their references (on the EASTBIO reference form template) to INCR.PostgraduateRecruitment@ed.ac.uk by the application deadline of 16th November 2026.
Funding Notes
This opportunity is open to UK and international students and provides funding covering stipend and UK level tuition fees. The University of Edinburgh covers the difference between home and international fees meaning that the EASTBIO DTP offers fully-funded studentships to all appointees. There is a cap on the number of international students the DTP recruits. It is therefore important for us to know from the outset which fees status category applicants will fall under when applying to our University.
Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.