Koh Research
Contact
233 South 10th Street
Room 219B
Philadelphia, PA 19107
We can't live without sleep and most of us sleep at night, but why we sleep and how sleep is regulated are not well understood. Our lab investigates the molecular and neural mechanisms of sleep and circadian rhythms using the fruit fly, Drosophila melanogaster, as a model system.
Research Projects
Discovery of Novel Sleep & Circadian Genes
Fly sleep is strikingly similar to human sleep. Since one of the strengths of the fly as a model system is that we can perform high-throughput genetic screens, our research strategy has been to find Drosophila mutants with strong and interesting sleep and circadian phenotypes and identify the genetic, molecular, and cellular basis for the phenotypes. From unbiased forward-genetic screens of several thousand mutant fly lines, we have discovered several novel genes and mutations that influence distinct aspects of sleep-wake cycles. sleepless (Koh et al, 2008; Wu et al, 2010) and taranis (Afonso et al, 2015) determine how much flies sleep, whereas wide awake (Sha et al, 2014) and dyschronic (Jepson et al, 2012) determine the timing of sleep. We are continuing to identify and characterize genes that affect sleep and circadian rhythms.
Sexually-dimorphic Regulation of Sleep
Whereas fly sleep is regulated by two main mechanisms, circadian and homeostatic, other factors also affect sleep. For example, male and female flies have distinct sleep patterns, indicating that sex also influences sleep. We recently identified a small number of neurons in the brain whose activation leads to markedly reduced sleep in male flies, but not in female flies. This is exciting because although several sleep-regulatory neuronal centers have been identified in Drosophila, this is the first example of a sexually-dimorphic arousal center. Using an array of genetic tools that are available for circuit analysis in Drosophila, we are determining the input signals and behavioral outputs of this neural center and its connectivity to other neuronal populations.
Sleep & Synaptic Plasticity
A substantial body of data suggests a complex relationship between sleep and synaptic plasticity. Several genes isolated in our screens for sleep and circadian mutants are known to be involved in synaptic development and plasticity. In addition, dyschronic, which was discovered in our screen for arrhythmic mutants (Jepson et al, 2012), also plays a role in synaptic development and function (Jepson et al, 2014). We are testing the hypothesis that dyschronic regulates rhythmic sleep patterns through its control of synaptic remodeling in adulthood.