Transcriptional analysis of the response of C. elegans to ethanol exposure

van Wijk, M. (Speaker), Sterken, M. (Contributor), Elizabeth Quamme (Contributor), Riksen, J. (Contributor), Lucinda Carnell (Contributor), Laura Mathies (Contributor), A. Davies (Contributor), Kammenga, J. (Contributor), Jill Bettinger (Contributor)

Activity: Talk or presentationOral presentationAcademic

Description

Ethanol consumption induces differential gene expression that are likely to at least partially underlie the progression to alcohol use disorder. We use C. elegans to study the effects of ethanol on nervous system function. To understand the gene expression dynamics that occur upon ethanol exposure, we conducted a time series experiment exposing C. elegans to a behaviorally intoxicating dose of ethanol for 30, 60, 120, and 480 minutes. The number of differentially expressed genes was positively correlated with exposure duration. We used K- means clustering to cluster genes based on expression over time and divided them in 5 distinct clusters. Gene ontology analysis showed enrichment for processes known to be involved in ethanol responses, for example: drug metabolism – cytochrome P450 and metabolic pathways. Furthermore, at eight hours of exposure several genes that are known to be involved in physiological response to ethanol were down regulated; some of those genes have been previously identified as direct ethanol targets, including the gene encoding the BK SLO-1 channel, the synaptic protein-encoding unc-13 gene, as well as genes involved in GABA signaling, suggesting a simple model in which downregulation of direct ethanol targets could decrease the depressing effects of ethanol and could contribute to the development of tolerance to ethanol.
Our exposure paradigm delivered ethanol in the absence of food, and we found that eight hours of food deprivation had a significant impact on overall gene expression as assessed by principal component analysis and transcriptional development analysis. Interestingly, ethanol was able to partially rescue the effect of food deprivation at eight hours, extending previous observations that C. elegans can use ethanol as a calorie source.
This timeseries captured gene expression dynamics in response to ethanol over time and will be used as a resource for our follow up studies, including investigating natural variation in gene expression in response to ethanol.
Period21 Jun 202124 Jun 2021
Event title23rd International C. elegans Conference : null
Event typeConference
Degree of RecognitionInternational