Whilst the effects and associated costs of excessive alcohol consumption in the human population are obvious at one level, the roles played by genetic factors at the molecular level are still unclear. Drosophila melanogaster has an alcohol response comparable to humans and is used as a genetic model to study the functional roles of genes regulated in response to ethanol. In the current study, the biological processes associated with behavioural responses to acute alcohol exposure in Drosophila have been analysed using whole genome expression profiling. Ethanol response genes differentially expressed (a) at a single time point (2 h) and (b) in a time series (0–4 h) were identified using microarrays. In addition, a subset of differentially expressed genes was validated using behavioural sedation and recovery assays. The study shows that genes involved in redox processes, neuron development, and specific signalling and metabolic pathways (including glutathione metabolism) form part of the response to ethanol in Drosophila. Biological processes for the regulation of oxidative stress are the common functional denominator of many of the ethanol response genes identified. These upregulated genes work to rescue cells from oxidative stress and its consequences such as protein misfolding, apoptosis and ageing. In the current study, an enrichment of Drosophila genes linked to ageing is observed for the first time. The functional genomics data revealed by such studies can be used to predict transcription networks of ethanol response genes, but the future lies in mapping these networks to the human population, with the ultimate aim of identifying genetic factors for alcohol use disorders.

Functional roles for redox genes in ethanol sensitivity in Drosophila

Automated measurement of Drosophila jump reflex habituation and its use for mutant screening.

The olfactory-jump response assay was used to analyze habituation in Drosophila mutants of potassium (K(+)) channel subunits. As with physiological assays of the giant fiber-mediated escape reflex, mutations at loci that encode K(+) channel subunits have distinct effects on habituating the olfactory-jump response. The data for slowpoke and ether a go-go indicate similar effects on habituation of the olfactory-jump response and the giant fiber-mediated escape. Habituation in the olfactory jump assay in Hyperkinetic and Shaker mutants was drastically different from the degree of defect in the giant fiber-mediated escape reflex, indicating differential control mechanisms underlying the two forms of non-associative conditioning.

Effects of mutant Drosophila K+ channel subunits on habituation of the olfactory jump response.

Stress plays an important role in drug- and addiction-related behaviours. However, the mechanisms underlying these behavioural responses are still poorly understood. In the light of recent reports that show consistent regulation of many genes encoding stress proteins including heat shock proteins following ethanol exposure in Drosophila, it was hypothesised that transition to alcohol dependence may involve the dysregulation of the circuits that mediate behavioural responses to stressors. Thus, behavioural genetic methodologies were used to investigate the role of the Drosophila hsp26 gene, a small heat shock protein coding gene which is induced in response to various stresses, in the development of rapid tolerance to ethanol sedation. Rapid tolerance was quantified as the percentage difference in the mean sedation times between the second and first ethanol exposure. Two independently isolated P-element mutations near the hsp26 gene eliminated the capacity for tolerance. In addition, RNAi-mediated functional knockdown of hsp26 expression in the glial cells and the whole nervous system also caused a defect in tolerance development. The rapid tolerance phenotype of the hsp26 mutants was rescued by the expression of the wild-type hsp26 gene in the nervous system. None of these manipulations of the hsp26 gene caused changes in the rate of ethanol absorption. Hsp26 genes are evolutionary conserved, thus the role of hsp26 in ethanol tolerance may present a new direction for research into alcohol dependency.

https://journals.sagepub.com/doi/pdf/10.4137/JEN.S6280

The Heat Shock Protein 26 Gene is Required for Ethanol Tolerance in Drosophila

ATP-binding cassette (ABC) transporters are widespread among organisms, and 56 genes encode ABC transporters in Drosophilamelanogaster (Meigen). Their functions are thought to be divergent. In this study, we examined whether there is a clock-related ABC transporter by performing genome-wide screening using tissue-specific RNA interference. We obtained five candidates when we used tim(UAS)-gal4, which expresses in virtually all clock-related cells. Because their phenotypes were principally reproducible even when we used pdf-gal4, which expresses in a subset of pacemaker neurons only, those transporters were presumed to function in pacemaker neurons. Those five candidates can be categorized into two groups according to the phenotype of the knockdown flies. In one group, CG9281 and CG15410 (E23), the circadian period of knockdown flies was altered. In the other group, CG5944, CG6052, and CG18633, some of the knockdown flies became arrhythmic whereas for others rhythmicity remained intact. Our results suggest that some ABC transporters that have a significant function in the Drosophila circadian system.

Genome-wide RNA interference screening for the clock-related gene of ATP-binding cassette transporters in Drosophila melanogaster (Diptera: Drosophilidae)

Most insertional mutagenesis screens of Drosophila performed to date have not used target chromosomes that have been checked for their suitability for phenotypic screens for viable phenotypes. To address this, we have generated a selection of stocks carrying either isogenized second chromosomes or isogenized third chromosomes, in a genetic background derived from a Canton-S wild-type strain. We have tested these stocks for a range of behavioral and other viable phenotypes. As expected, most lines are statistically indistinguishable from Canton-S in most phenotypes tested. The lines generated are now being used as target chromosomes in mutagenesis screens, and the characterization reported here will facilitate their use in screens of these lines for behavioral and other viable phenotypes.

Isogenic autosomes to be applied in optimal screening for novel mutants with viable phenotypes in Drosophila melanogaster

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Kits Krishnan

Author Tools

Chat about Author

Papers

Isogenic autosomes to be applied in optimal screening for novel mutants with viable phenotypes in Drosophila melanogaster