Wellcome Trust Centre For Mitochondrial Research

Amy Reeve

Biography

Dr Amy Reeve

I first became interested in mitochondrial biology in 2004 when I came to Newcastle to study for my PhD. My PhD project investigated the importance of mitochondrial dysfunction to neurodegeneration, with a particular focus on Parkinson’s.

Since completing my PhD my research has focussed on understanding whether neurons are capable of adapting to mitochondrial dysfunction and whether this is something that we might be able to promote using drugs. My primary interest still lies in investigating these changes in relation to Parkinson’s and this forms the basis of my Parkinson’s UK Fellowship (F-1401).

In order to understand the importance of mitochondrial defects to neuron loss in Parkinson’s we study a number of different aspects of mitochondrial biology from their structure and dynamics, to their neuronal location and calcium buffering capabilities.

 

Research Project

Principal Investigator: Dr Amy Reeve
Other staff members involved: Chen Chun, Nishani Jeyapalan and Lizzie Stephen

Project Details

  • Investigating the subcellular distribution of mitochondria in dopaminergic neurons – Recently we found that the distribution of mitochondria to the distal parts of neurons (synapses and axons) was altered in Parkinson’s and we uncovered a population of synapses which were devoid of mitochondrial proteins. We are investigating whether this is evidence of an adaptation to mitochondrial dysfunction and the role which astrocytes play in supporting and modulating neuronal mitochondrial populations. We are also examining the ultrastructure of these mitochondria using 3View.
  •  Investigating the impact of mitochondrial dysfunction on the movement of mitochondria within dopaminergic neurons – The movement of mitochondria around dopaminergic neurons is essential to ensure energy provision to support neuronal function. We study the impact of mitochondrial dysfunction and alpha-synuclein on the movements of mitochondria in model systems.
  • Investigating the consequence of mitochondrial dysfunction – Using Image mass cytometry, a cutting edge technology which enables up to 30 protein targets to be examined in a single neuron we are gathering information about the response of neurons to mitochondrial defects and alpha-synuclein accumulation.
  • Screening for compounds and molecules which protect dopaminergic neurons against mitochondrial dysfunction – We are working with collaborators within the centre to design a system in which we can screen for compounds which are capable of improving the survival of dopaminergic neurons with mitochondrial defects.

 

Funding

  • Awarded a £136,677 Michael J Fox Foundation Mitochondrial Biomarkers program grant (2018-2020).
  • Awarded a £164,000 Senior Fellowship extension by Parkinson’s UK (2017-2019)
  • Awarded a £250,000 Career Development Award by Parkinson’s UK (2014-2017)

 

Selected Publications

 Scopus h-index=21 and ResearchGate Score=33.89 (calculated August 2018).

  1. Reeve AK et al. Mitochondrial dysfunction within the synapses of substantia nigra neurons in Parkinson’s disease. NPJ Parkinsons Dis. 2018 Mar 26;4:9.
  2. Reeve AK et al. Aggregated α-synuclein and complex I deficiency: exploration of their relationship in differentiated neurons. Cell Death Dis. 2015 Jul
  3. Reeve AK, et al. The impact of pathogenic mitochondrial DNA mutations on substantia nigra neurons. Journal of Neuroscience. 2013. 33(26):10790-10801
  4. Campbell GR, Reeve A, Ziabreva I, Polvikoski TM, Taylor RW, Reynolds R, Turnbull DM, Mahad DJ. Mitochondrial DNA deletions and depletion within paraspinal muscles. Neuropathol Appl Neurobiol. 2013 Jun;39(4):377-89
  5. Campbell GR, Kraytsberg Y, Krishnan KJ, Ohno N, Ziabreva I, Reeve A et al. Clonally expanded mitochondrial DNA deletions within the choroid plexus in multiple sclerosis. Acta Neuropathol. 2012 24(2):209-20
  6. Campbell GR, Reeve A, et al. Mitochondrial DNA deletions and depletion within paraspinal muscles. Neuropathol Appl Neurobiol. 2012. 39(4):377-89
  7. Lax NZ, Pienaar IS, Reeve AK et al. Microangiopathy in the cerebellum of patients with mitochondrial DNA disease. Brain. 2012. 135 (Pt 6):1736-50
  8. Lax NZ, Campbell GR, Reeve AK et al. Loss of myelin-associated glycoprotein in Kearns-Sayre syndrome. Arch Neurol. 2012;69(4):490-9
  9. Reeve AK et al. The relationship between mitochondria and α-synuclein – A study of single substantia nigra neurons. Arch Neurol. 2012 69(3):385-93
  10. Lax NZ, Hepplewhite PD, Reeve AK et al. Cerebellar Ataxia in Patients With Mitochondrial DNA Disease: A Molecular Clinicopathological Study. J Neuropathol Exp Neurol. 2012;71(2):148-161.
  11. Lax NZ, Whittaker RG, Hepplewhite PD, Reeve AK et al. Sensory neuronopathy in patients harbouring recessive polymerase γ mutations. Brain. 2011 135(Pt 1):62-71
  12. Campbell GR, Ziabreva I, Reeve AK et al. Mitochondrial DNA deletions and neurodegeneration in multiple sclerosis. Ann Neurol. 2011;69(3):481-92
  13. Reeve AK et al. The low abundance of clonally expanded mitochondrial DNA point mutations in aged substantia nigra neurons. Aging Cell. 2009;8(4):496-8
  14. Betts-Henderson J, Jaros E, Krishnan KJ, Perry RH, Reeve AK et al. Alpha-synuclein pathology and Parkinsonism associated with POLG1 mutations and multiple mitochondrial DNA deletions. Neuropathology and Applied Neurobiology. 2009;35(1):120-4
  15. Krishnan KJ, Reeve AK et al. What causes mitochondrial DNA deletions in human cells? Nature Genetics. 2008;40(3):275-9
  16. Reeve AK et al. Nature of mitochondrial DNA deletions in substantia nigra neurons. American Journal of Human Genetics. 2008;82(1):228-35
  17. Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK et al. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nature Genetics. 2006;38(5):515-7