During the final year project of my Pharmacology undergraduate degree, completed here at Newcastle University, I became fascinated by the role of mitochondrial dysfunction in neurodegenerative disease. This interest led me to undertake an MRes in Ageing and Health, during which my fascination into age associated mitochondrial disease deepened, and then finally here to embarking on a PhD at the Wellcome Trust Centre for Mitochondrial Research.
Nanobiopsy: a tool for mitochondrial research
Other Team Members Involved: Dr Angela Pyle
Mitochondrial DNA (mtDNA) exists as multiple molecules in all mitochondria.
Whilst the default state of mtDNA is of homoplasmy, in which only the wild-type mtDNA genome exists, random somatic mutations can occur as a result of daily living and this results in heteroplasmy (a mixture of wild-type and mutant mtDNA). Somatic mutations in mtDNA can occur and accumulate over a life time, through a process known as clonal expansion, and above a threshold level causes mitochondrial dysfunction and ultimately cell death.
Current techniques allow us to sequence mtDNA variants and determine the relative abundance of total and mutant mtDNA – even at the single cell level. This, however, necessitates the lysis of cells. We hope that serial extraction of mitochondria from live cells over time, using a technique called nanobiposy, will allow us to better understand the process of clonal expansion of mutant mtDNA and its role in disease pathophysiology.
Sponsor/funder: DiMeN (Discovery Medicine North), MRC
Bury A.G., Robertson F.M., Pyle A, Payne B.A.I., Hudson G. The Isolation and Deep Sequencing of Mitochondrial DNA. (2021) Methods Mol Biol. 2277 doi: 10.1007/978-1-0716-1270-5
Bury, A., Vincent, A., Turnbull, D., Actis, P. and Hudson, G. (2020) Mitochondrial isolation: when size matters. Wellcome Open Research. 5, 226
Bury, A.G., Pyle, A., Elson, J.L., Greaves, L., Morris, C.M., Hudson, G. et al. (2017) Mitochondrial DNA changes in pedunculopontine cholinergic neurons in Parkinson disease. Ann. Neurol. 82, 1016–1021