9602119 Jackson Circadian clocks located in the brains of all animal species are essential for the regulation of daily rhythms in many different physiological, endocrine, and behavioral processes. Such clocks, for example regulate the timed release of hormones, the timing of waking and sleeping, and even the changing sensitivity of animals and humans to pharmacological agents used in the treatment of cancer and other diseases. Circadian clocks can be reset by light stimuli and this is crucial for the synchronization of these clocks to environmental light/dark cycles. The proper synchronization of circadian clocks to environmental time (solar time) is essential and insures that physiological processes (within an organism's body) occur at an appropriate time of day and in a coordinated manner. Indeed, most travelers are aware of the phenomenon of jet- lag, which results from a desynchronization of bodily rhythms during adaptation to a new time zone. Although it is known that light can reset the circadian clock, the exact mechanism by which the nerve cells comprising the clock transduce light information into a resetting response is not well understood. The major purpose of this grant is to define and study the signaling pathways within clock neurons which are activated during the clock resetting response. This work will be accomplished using the model genetic system Drosophila melanogaster and contemporary molecular biological approaches. It will also take advantage of existing Drosophila mutants which have heritable lesions affecting specific cellular signaling pathways. The significance of this work is that it will lead to a more complete understanding of how the brain's clock is reset by environmental signals such as light.
