Academic Background

Circadian Rhythms and their Synchronization in Drosophila

Drosophila melanogaster is a powerful model organism for understanding the genetic, molecular and neural bases of animal behaviors. Circadian rhythms are a prime example of behaviors whose molecular and neural foundations have been greatly increased by studies in Drosophila.  A biological clock dictates that animals sleep and wake with a ca. 24-hour period, and this is true even when they are kept under constant conditions, without any information from the environment. Using genetic screens, many essential clock proteins (e.g. PER, TIM, figure 1) were identified in Drosophila. It has been shown that homologues of most of these proteins are also involved in generating mammalian circadian rhythms.  Human homologues of Drosophila PER (hPER2) and DBT (hCK-Id) are actually mutated in patients with advanced sleep-phase syndrome. This demonstrates that the discoveries made in Drosophila are playing a crucial role in understanding human circadian behavior.

Since the period of circadian rhythms only approximates 24 hours, and since photoperiod changes at most latitudes over the course of the year, it is essential for circadian rhythms to be responsive to environmental light and temperature cues to remain properly phased with the day/night cycle.  We are combining the powerful genetics of Drosophila with behavioral, cell culture, molecular and biochemical approaches to obtain a comprehensive understanding of the mechanisms underlying the synchronization of Drosophila circadian rhythms. 

One of our major goals is to identify the proteins controlling circadian light and temperature responses and understand their function. We are particularly interested in the mechanisms by which CRYPTOCHROME (CRY) - an unusual blue-light photoreceptor - resets the circadian clock (figure 2).  Interestingly CRY is expressed directly within the neurons that control circadian behavior and is therefore a deep-brain photoreceptor.  In recent years, it has become clear that specific circadian neurons have dedicated function in the control and synchronization of circadian behavior.  Therefore, a second major objective of our laboratory is to identify the circadian neurons responsive to light and temperature, and to understand with precision how these neurons contribute to synchronize circadian behavior with the day/night cycle.

In summary, our work is aimed at discovering the molecular and neural mechanisms underlying the synchronization of circadian rhythms with light and temperature cycles.  Our ultimate goal is to understand how circadian clocks integrate these different inputs to optimize daily animal physiology and behavior.  

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