Parkinson’s disease risk genes and their effect on behaviour in Drosophila melanogaster

Abstract

Over 90 single nucleotide polymorphisms have been associated with increased risk of Parkinson’s disease however it is unknown how these contribute to disease phenotypes. Bioinformatic tools were used to identify orthologs of the candidate genes for SNPs in Drosophila melanogaster. A screen of 19 orthologs was performed and the startle-induced negative geotaxis assay, eye degeneration and Drosophila Activity Monitor 2 system was used to characterise locomotor, degeneration and sleep and circadian phenotypes of flies respectively. It was identified that knockdown of CaMKII, comt, fray, nsl1, tutl, EndoA, Hip1 and Dh44-R1 in neurons produce phenotypes relevant to Parkinson’s disease. The memory phenotypes of flies expressing α-synuclein in the mushroom body were characterised using aversive olfactory conditioning. α-synuclein expression in the mushroom body eliminated intermediate memory, however this was not related to changes in Ca2+ transients. Together, this study proves that Drosophila are a useful tool to screen for behavioural changes in Parkinson’s disease and identified genes to be further characterised.

Date of Award	24 Jan 2023
Original language	English
Awarding Institution	University of Bristol
Supervisor	James J L Hodge (Supervisor)