Alzheimer's Research UK Fellow
I am a molecular genetist, with a particular interest in using Drosophila melanogaster as a model for ageing and neurodegeneration studies. I worked as a postdoctoral research associate in the Institute for Healthy ageing (UCL), in the lab of Professor Dame Linda Partridge and carried out research into the role of dFOXO, the key transcription factor in the insulin/insulin-like signalling pathway in Drosophila. I came to the University of Cambridge with a fellowship by Alzheimer's Research UK to investigate the role of ageing as a risk factor for Alzheimer's Disease.
Investigating Ageing and Alzheimer's Disease interactions using Drosophila
Ageing is the highest risk factor for Alzheimer’s disease (AD) and other dementias. AD is a progressive neurodegenerative disease, characterised by neuronal and synaptic loss resulting in cognitive impairment and a gradual loss of memory, language skills and reasoning leading to dementia and finally death. AD is characterised by the presence of two pathologies, extracellular plaques (primarily accumulations of a peptide called amyloid b) and intracellular tangles (accumulations of hyperphosphorylated tau protein).
Ageing is an evolutionarily conserved process and various pathways have been described which determine lifespan. Manipulation of these pathways has been shown to delay ageing and also delay the onset of neurodegenerative diseases.
AD is modelled in the fruitfly Drosophila by expressing the amyloid beta peptide as a secreted protein from the neurons of the fly and this leads to progressive accumulation of this peptide, a decline in climbing ability and finally death, recapitulating many of the features of the human disease.
I am interested in understanding why ageing is the main risk factor for AD and specifically what changes in the brains of older individuals that makes them more susceptible to disease.
More specifically I am:
- Using a systems biology approach to investigate the expression of genes in AD and control flies and identify processes changing in AD and ageing
- Investigating the effect of manipulating candidate AD modifiers in the AD fly model
- Identification of novel modifiers of Aβtoxicity by transcriptomic analysis in the fruitfly. Favrin G, Bean DM, BilslandE, BoyerH, Fischer BE, Russell S, Crowther DC, Baylis HA, OliverSG, Giannakou ME. Sci Reports. 2013 Dec 16;3, 3512.
- Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling. Alic N, Andrews TD, Giannakou ME, Papatheodorou I, Slack C, Hoddinott MP, Cochemé HM, Schuster EF, Thornton JM, Partridge L. Mol Syst Biol. 2011 Jun 21;7:502.
- dFOXO-independent effects of reduced insulin-like signaling in Drosophila. Slack C, Giannakou ME, Foley A, Goss M, Partridge L. Aging Cell. 2011 Oct;10(5):735-48. Epub 2011 May 6.
- Role of dFOXO in lifespan extension by dietary restriction in Drosophila melanogaster: not required, but its activity modulates the response. Giannakou ME, Goss M, Partridge L. Aging Cell. 2008 Mar;7(2):187-98. Epub 2008 Jan 30.
- Dynamics of the action of dFOXO on adult mortality in Drosophila. Giannakou ME, Goss M, Jacobson J, Vinti G, Leevers SJ, Partridge L. Aging Cell. 2007 Aug;6(4):429-38. Epub 2007 Apr 26.
- Long-lived Drosophila with overexpressed dFOXO in adult fat body. Giannakou ME, Goss M, Jünger MA, Hafen E, Leevers SJ, Partridge L. Science. 2004 Jul 16;305(5682):361. Epub 2004 Jun 10.
Drosophila melanogaster as a Model Organism for Dementia. Giannakou ME, Crowther DC Chapter in book: Animal models of dementia. Editors: De Deyn PP, van Dam D. Humana Press 2010
Role of insulin-like signalling in Drosophila lifespan. Giannakou ME, Partridge L. Trends Biochem Sci. 2007 Apr;32(4):180-8. Epub 2007 Apr 6. Review.