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Contact Information
Research InterestsHow does a fruit fly know the time of day? Actually, Drosophila as well as many other organisms ranging from cyanobacteria to humans has an internal circadian clock that allow it to keep its bodily functions and behavior on a daily schedule. My laboratory is interested in understanding the molecular background of this phenomenon. The brains of both flies and humans have specialized pacemaker neurons that control sleep/wake behavior, but functional molecular clock circuits are found in many other tissues as well. At their most basic level, circadian clocks consist of a set of transcriptional feedback loops that serve to both keep the clock running and to send rhythmic output signals for control of behavior and bodily functions (for more details see Figure 1). We conducted a genome-wide transcript profiling study on microarrays aimed at identifying all clock-controlled transcripts that act in the core feedback loop mechanisms or in clock output pathways. Application of fourier and autocorrelation analyses to our microarray time course data allowed us to discover a wealth of novel circadian transcript profiles (Figure 2). The confirmed and predicted functions of these transcripts indicated circadian control for a range of biological functions including vision, olfaction, synaptic function, metabolism, and detoxification. We are now pursuing genetic, molecular, and behavioral analyses that will allow us to determine how the extensive program of circadian transcript expression is organized into output pathways. In further genome-wide studies
using behaviorally arrhythmic mutant flies we showed that while no true
circadian transcript oscillations are detectable in the absence of a
clock, a limited number of transcripts show rhythmic expression when
driven by a daily light/dark cycle. Interestingly, these light-responsive
transcripts are preferentially expressed in the adult compound eyes
and tend to also show circadian oscillations. The coupling of photic
and clock-controlled signals that we observed at the transcript level
is potentially important for the solidification of light-dependent entrainment
of the clock. In addition, the dual photic and circadian control of
transcripts may allow light-dependent modulation of a specific set of
circadian outputs, including phototransduction or synaptic function.
We are currently examining these hypotheses.
Representative Publications
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