Burns, Andrew R. et al. (2011) International Worm Meeting "Samamide is a new small-molecule probe of behavioural quiescence in C. elegans."

Hampson, David R., Roy, Peter J., Tharmalingalam, Suji, Burns, Andrew R., Ryu, William S., Cutler, Sean R.

[International Worm Meeting, 2011]

C. elegans displays at least three distinct behavioural quiescent states. First, a sleep-like state is induced by epidermal growth factor signalling before each larval molt. Second, satiation induces a quiescent state that is regulated by both TGF-b and insulin signalling. Finally, adult worms cycle through periods of quiescence after prolonged swimming. In all three cases, the C. elegans cGMP-dependent protein kinase (PKG) homolog egl-4 promotes quiescence. It has been shown that increased PKG activity in Drosophila promotes sleep, and PKG1 inhibition in mouse brain alters the sleep-wake distribution, suggesting phylogenetic conservation of factors that regulate sleep and perhaps behavioural quiescence in general. In a screen of 4,000 drug-like chemicals we identified a previously uncharacterized molecule that we hypothesize is promoting quiescence during swimming. We call this molecule 'samamide'. Reduced swimming activity is observed in adult worms treated acutely with samamide, suggesting that the chemical alters the physiological state of the animal. Chemical-genetic analyses suggest that samamide promotes quiescence by modulating metabotropic glutamate receptor activity. Samamide holds promise as a unique tool to better understand behavioural quiescence in animals.