The circadian clock is the most well studied of all the biological clocks. The first clock gene, period, was identified in the fruit fly through mutagenesis in 1971. The discovery of the molecular clock mechanism led to the Nobel Prize in Physiology and Medicine to Michael W. Young, Michael Rosbash and Jeffrey C. Hall (2017).
These three American fly geneticists discovered the negative feedback mechanism at the heart of the circadian clock. The transcription of the genes timeless (tim) and period (per) is driven by the transcription factors CLOCK and CYCLE. Once TIM and PER are produced in clock cells they migrate back into the nucleus and they inhibit their own transcription by sequestering CLOCK and CYCLE. Their concentration in the cytoplasm is critical to determine when they will move back into the nucleus and it is regulated by post translational modifications.
For many years the circadian community has been studying the molecules involved in this feedback loop, and the biochemistry of the clock proteins’ interactions. More recently we are focusing our attention on how the circadian clock controls behaviour. Around 150 the clock neurons (neurons expressing clock genes) have been identified in the fly brain, and their projections have been mapped. We are studying how the interactions between different groups of clock neurons can generate circadian rhythms.