Our Team

I use a genetic approach with the model organism Caenorhabditis elegans to identify molecular targets of drugs and to better understand the response of the nervous system to the presence of these drugs. In particular I have focused primarily on the effects of alcohol on the nervous system. As occurs with humans, C. elegans display concentration-dependent alterations in behaviors when intoxicated by alcohol. By concentrating on the depressive effects of alcohol on speed of locomotion using object recognition software to track individual C. elegans, I have been able to identify multiple genetic mutants that display altered sensitivity to the behavioral effects of alcohol. These mutants have identified several mechanisms for the action of ethanol, including direct activation of the BK channel SLO-1, neuropeptide signaling and processing, and a ligand-gated ion channel, still under investigation. The identification of genes that mediate alcohol’s effects in C. elegans provide candidates for genes that play similar roles in humans. Genes that affect an individual’s acute sensitivity to the drug may be important in predisposing an individual to alcohol use disorders (AUDs) because there is a strong correlation between a naïve drinker’s level of tolerance to alcohol and their likelihood of abusing alcohol later in life.

Further, in collaboration with members of the VCU Alcohol Research Center, I also take a cross-species approach, examining C. elegans orthologs of mouse and human candidate genes for roles in mediating behavioral responses to alcohol. In this way, we can identify human genetic variation that is likely to be important in predisposition to developing an AUD, and/or genes that play a role in modulating alcohol responses and consumption in mice.

Selected publications

Mathies LD, Blackwell GG, Davies AG, Bettinger JC. (2026) SWI/SNF complexes modulate gene expression and the development of physical dependence to ethanol. Alcohol Clin Exp Res 50(1):e70223. PMID: 41527326 (PubMed).

Lindsay JH, Mathies LD, Davies AG, Bettinger JC. (2022) A neuropeptide signal confers ethanol state dependency during olfactory learning in Caenorhabditis elegans. Proc Natl Acad Sci USA. 119(46):e2210462119 (PubMed).

Aliev F, Barr PB, Davies AG, Dick DM, Bettinger JC. (2022) Genes regulating levels of ω-3 long-chain polyunsaturated fatty acids are associated with alcohol use disorder and consumption, and broader externalizing behavior in humans. Alcohol Clin Exp Res. 46(9):1657-1664. PMID: 35904282 (PubMed).

Sterken MG, van Wijk MH, Quamme EC, Riksen JAG, Carnell L, Mathies LD, Davies AG, Kammenga JE, Bettinger JC. (2021) Transcriptional analysis of the response of C. elegans to ethanol exposure. Sci. Rep. 11: 10993. PMID: 34040055 (PubMed)

Wolstenholme JT, Bowers MS, Pais AB, Pais AC, Poland RS, Poklis JL, Davies AG, Bettinger JC. (2018) Dietary omega-3 fatty acids differentially impact acute ethanol-responsive behaviors and ethanol consumption in DBA/2J versus C57BL/6J mice Alcohol. Clin. Exp. Res. 42: 1476-1485. PMID: 29786878 (PubMed)

Mathies LD, Blackwell GG, Austin MK, Edwards AC, Riley BP, Davies AG, Bettinger JC. (2015) SWI/SNF chromatin remodeling regulates alcohol response behaviors in Caenorhabditis elegans and is associated with alcohol dependence in humans. Proc Natl Acad Sci U S A. 112(10):3032-3037. PMID: 25713357 (PubMed)

Davies AG, Blackwell GG, Raabe RC, Bettinger JC (2015) An assay for measuring the effects of ethanol on the locomotion speed of Caenorhabditis elegans. J Vis Exp. Apr 9;(98). doi: 10.3791/52681. PMID: 25938273 (PubMed)

Hawkins EG, Martin I, Kondo LM, Judy ME, Brings VE, Chan C-L, Blackwell GG, Bettinger JC, Davies AG. (2015) A novel cholinergic action of alcohol and the development of tolerance to that effect in Caenorhabditis elegans. Genetics 199(1):135-149. PMID: 25342716 (PubMed)

Raabe RC, Mathies LD, Davies AG, Bettinger JC. (2014) The omega-3 fatty acid eicosapentaenoic acid is required for normal alcohol response behaviors in C. elegans. PLoS One 9:e105999. PMID: 25162400 (PubMed)

Davies AG, Friedberg RI, Gupta H, Chan C-L, Shelton KL, Bettinger JC. (2012) Different genes influence toluene- and ethanol-induced locomotor impairment in C. elegans. Drug Alcohol Depend. 122: 47-54. PMID: 21945072 (PubMed)

Bhandari P., Hill JS, Farris SP, Costin B, Martin I, Chan C-L, Alaimo JT, Bettinger JC, Davies AG, Miles MF, Grotewiel M. (2012) Chloride intracellular channels modulate acute ethanol behaviors in Drosophila, C. elegans and mice. Genes Brain Behav. 11:387-397. PMID: 22239914 (PubMed)

Bettinger JC, Leung K, Bolling MH, Goldsmith AD, Davies AG. (2012) Lipid environment modulates the development of acute tolerance in Caenorhabditis elegans. PLoS One 7(5):e35192. PMID: 22574115 (PubMed)