Animals from cnidarians to vertebrates engage in sleep - quickly reversible periods of behavioral quiescence that are associated with reduced sensory responsiveness. Though the cellular function of sleep is of debate, its benefit is inarguable, and sleep loss is associated with a wide range of adverse effects from impairments in cognitive function to death. Interestingly, sleep in C. elegans does not appear to fall under circadian regulation. This nematode sleeps at the end of each larval molt during a period known as developmentally-timed sleep (DTS) or lethargus (Raizen et al., 2008). C. elegans also sleeps during recovery from exposure to damaging conditions - a phenomenon referred to as stress-induced sleep (SIS) (Hill et al., 2014; Nelson et al., 2014). Despite their phenotypic similarity, DTS and SIS are regulated by largely independent genetic and neural circuits (Trojanowski and Raizen, 2015). DTS is linked to the molting cycle and depends on the release of sleep-promoting
flp-11 neuropeptides from the RIS interneuron (Turek et al., 2016). By contrast, SIS is triggered by conditions that cause cellular damage and is dependent on EGF signaling within the peptidergic ALA neuron and the collective action of a distinct set of ALA-expressed neuropeptides (Hill et al., 2014, Nelson et al., 2014, Nath et al., 2016). Engagement in SIS appears to be beneficial, as sleep-defective mutants are impaired for recovery following exposure to damaging conditions (Hill et al., 2014; Fry et al., 2016). We posit that SIS reveals a deeply conserved phenomenon, and that a core function of sleep is to repair cellular damage that accrues during wakefulness. In support of this notion, recent studies in zebrafish have shown that the number of double-strand breaks (DSBs) in neuronal nuclei increases during the day and that sleep promotes chromosome dynamics that are required for DSB repair (Zada et al., 2019). We are therefore interested in identifying additional components of SIS in C. elegans, with the goal of characterizing this potentially deeply conserved phenomenon. To this end, we are performing forward genetic screens for SIS-defective mutants, and we are doing this within the context of an undergraduate laboratory course at CSUN called BIOL447: FIRE (Full Immersion Research Experience). We will present several SIS components that we have identified thus far through mapping and whole-genome sequencing of our SIS-defective mutants.