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Title: Testing and identifying potential gerontogenes as potential drug targets using the model organism Drosophila melanogaster
Author: Birdsall, John Peter
ISNI:       0000 0004 6424 7897
Awarding Body: Lancaster University
Current Institution: Lancaster University
Date of Award: 2015
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Ageing is an inexorable process which we all suffer from. The cost of ageing on society is in the billions yet much research is involved in tackling the individual age associated disease. Manipulations of single genes in D. melanogaster and C. elegans have been shown to extend lifespan and are potential targets for therapy. Identification of these potential gerontogenes arises mainly from screening studies and research on pathways known to be involved in ageing (such as insulin signalling pathway and dietary restriction), but with the improvements in bioinformatics techniques, whole genome analysis can be carried out to identify changes in expression levels over time and under specific conditions. Here we have tested a number of candidate genes; identified from a previous microarray study comparing expression profiles over time of control and dietary restricted (DR) flies, the genes were concurrently up or down regulated in both normal ageing and under DR conditions. We used the transgenic Geneswitch technique to ubiquitously mis­express genes of interest returning their old expression levels to that of younger flies to mimic drug therapy. We also tested two previously identified gerontogenes (chico and hsp27] using the Geneswitch technique to test as potential targets as well as further define the parameters of their lifespan extending effects. Finally, in an attempt to identify other potential gerontogenes, two large scale gene expression microarrays were analysed. The first microarray focussed on the differential expression between germ-line and somatic cells of Drosophila, the second looked at expression levels over time in both male and female flies. The study of the two previous gerontogenes further strengthened the sex-specific effects of chico and highlights the importance of genetically equivalent controls in regards to hsp27. Testing of the potential gerontogenes identified many aspects of the Geneswitch system which need to be properly addressed when used for lifespan experiments. Finally, 25 potential gerontogenes were identified from analysis of the germ/soma study and 12 from the expression over time study which require further testing to validate.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available