Lunnon

[Fees plus a stipend of £21,805 per annum for 2026/7.] PhD studentship at the University of Exeter on mapping and functional interrogation of mitochondrial DNA modifications in Parkinson’s disease. This project investigates how DNA modifications in the mitochondrial genome may regulate mitochondrial function and contribute to Parkinson’s disease. Using Oxford Nanopore long-read sequencing on native enriched mtDNA, the project will develop and validate approaches to detect multiple DNA modifications directly on individual molecules, including 5mC, 5hmC and 6mA. It will then apply these methods to a well-characterised Parkinson’s disease brain cohort to study the distribution, abundance and disease-associated differences in mtDNA modification patterns across the mitochondrial genome, including regulatory regions such as the D-loop. The research is highly interdisciplinary and combines mitochondrial genetics, epigenetics, long-read sequencing, bioinformatics and multi-omic data integration. A further aim is to test the functional relevance of mtDNA modification states by integrating them with mitochondrial transcription, mtDNA abundance, bulk and snRNA-seq, small RNA-seq, nuclear DNA methylation and genetic data from the same brains. This should help identify candidate regulatory modifications for future causal studies using emerging mitochondrial epigenome-editing approaches. The supervisory team includes Prof Lunnon, Prof Chinnery, Dr Kouhsar and Dr Smith, bringing complementary expertise in neurodegenerative disease epigenetics, mitochondrial genetics, bioinformatics, multi-omic analysis and Oxford Nanopore method development. The project will use existing Parkinson’s disease brain samples, matched genomic and transcriptomic datasets, and established sequencing/computational infrastructure at Exeter. Funding is provided by the Medical Research Council (MRC). The studentship covers fees plus a stipend of £21,805 per annum for 2026/7. The application deadline is 08 Dec 2026.