Wellcome Trust Centre For Mitochondrial Research

Alexander Bury

Biography

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.

Research Project

A longitudinal study of mtDNA variant selection enabled by single-cell nanobiopsy

Principal Investigators: Dr Gavin Hudson, Dr Amy Vincent, Dr Paolo Actis, Professor Doug Turnbull

Project Details

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.

Contact: a.g.bury@ncl.ac.uk

Sponsor/funder: DiMeN (Discovery Medicine North), MRC

Publications:

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

Pienaar I. S., Harrison I. F., Elson J. L., Bury A.G., Woll P., Simon A. K., et al. (2015). An animal model mimicking pedunculopontine nucleus cholinergic degeneration in Parkinson’s disease. Brain. Struct. Funct. 220, 479–500. 10.1007/s00429-013-0669-5