Gene regulation in Drosophila melanogaster in response to an acute dose of ethanol

• Main Author: Awofala, Awoyemi Abayomi
• Published: University of Sussex 2010
• Subjects: 591.35; QL Zoology
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.554588

Alcohol intake causes gene expression changes resulting in cellular and molecular adaptations that could be associated with a predisposition to alcohol dependence. Expression profiling using high-throughput microarrays has recently been used to identify changes in gene expression that may be associated with alcohol dependence. To clarify the mechanisms and biology underlying alcohol dependence, bioinformatics, behavioural and genetics methodologies were employed to analyse obtained raw microarray data set that was previously generated from Drosophila exposed to an acute dose of ethanol. Classical linear statistical modeling coupled with clustering and functional enrichment analyses were implemented to evaluate whole-head time series microarray data from ethanol-treated and control samples, and implicated many genes or pathways affected by acute ethanol treatment in Drosophila head including those involved in stress signaling, inter and intra cellular signaling, ubiquitinmediated signaling, metabolic switches, and possible transcriptional regulatory components. Further analysis identified interaction networks and patterns of transcriptional regulation within the set of identified genes. Seven of these genes, ana, Axin, hiw, hop, hsp26, hsp83, and mbf1, were verified and linked with novel roles in ethanol behavioural responses using functional tests. Additional work on two of these genes namely, hiw and hsp26 also revealed a role for glia, mushroom bodies and ellipsoid body neurons as important regulators of acute ethanol response in Drosophila. Finally, these studies have demonstrated that microarray analysis is an efficient method for identifying candidate genes and pathways that may be fundamental to human alcohol dependence or abuse.