Casein kinase 1 promotes synchrony of the circadian clock network.

Casein kinase 1, known as DOUBLETIME (DBT) in Drosophila melanogaster, is a critical component of the circadian clock that phosphorylates and promotes degradation of the PERIOD (PER) protein. However, other functions of DBT in circadian regulation are not clear, in part because severe reduction of dbt causes preadult lethality. Here we report the molecular and behavioral phenotype of a viable dbt(EY02910) loss-of-function mutant.

Day-night cycles and the sleep-promoting factor, Sleepless, affect stem cell activity in the Drosophila testis.

Adult stem cells maintain tissue integrity and function by renewing cellular content of the organism through regulated mitotic divisions. Previous studies showed that stem cell activity is affected by local, systemic, and environmental cues. Here, we explore a role of environmental day-night cycles in modulating cell cycle progression in populations of adult stem cells.

Cooperative interaction between phosphorylation sites on PERIOD maintains circadian period in Drosophila.

Circadian rhythms in Drosophila rely on cyclic regulation of the period (per) and timeless (tim) clock genes. The molecular cycle requires rhythmic phosphorylation of PER and TIM proteins, which is mediated by several kinases and phosphatases such as Protein Phosphatase-2A (PP2A) and Protein Phosphatase-1 (PP1). Here, we used mass spectrometry to identify 35 "phospho-occupied" serine/threonine residues within PER, 24 of which are specifically regulated by PP1/PP2A.

Genetic and anatomical basis of the barrier separating wakefulness and anesthetic-induced unresponsiveness.

A robust, bistable switch regulates the fluctuations between wakefulness and natural sleep as well as those between wakefulness and anesthetic-induced unresponsiveness. We previously provided experimental evidence for the existence of a behavioral barrier to transitions between these states of arousal, which we call neural inertia. Here we show that neural inertia is controlled by processes that contribute to sleep homeostasis and requires four genes involved in electrical excitability: Sh, sss, na and unc79.

Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations.

Sleep-wake cycles break down with age, but the causes of this degeneration are not clear. Using a Drosophila model, we addressed the contribution of circadian mechanisms to this age-induced deterioration. We found that in old flies, free-running circadian rhythms (behavioral rhythms assayed in constant darkness) have a longer period and an unstable phase before they eventually degenerate.

An isoform-specific mutant reveals a role of PDP1 epsilon in the circadian oscillator.

The Drosophila PAR domain protein 1 (Pdp1) gene encodes a transcription factor with multiple functions. One isoform, PDP1epsilon, was proposed to be an essential activator of the core clock gene, Clock (Clk). However, a central clock function for PDP1epsilon was recently disputed, and genetic analysis has been difficult due to developmental lethality of Pdp1-null mutants.