Medicine Nobel Prize 2017 goes to Circadian Clock Specialists
The Nobel prize 2017 for physiology or medicine has been awarded to three neurogeneticists who uncovered the mechanisms of the circadian clock in Drosophila melanogaster.
After the isolation of the first clock mutants by Konopka and Benzer in 1971, the laboratories of Jeff Hall and Michael Rosbash at Brandeis University and the one of Mike Young at Rockefeller university identified the period gene in the early 80s. This was one of the very first “behavioral genes” to be identified and the analysis of its regulation led the Brandeis groups to propose a negative feed-back loop mechanism whereby the cycling PERIOD protein represses the transcription of its own gene.
In the 90s, the Young lab isolated TIMELESS, the partner of PERIOD for transcriptional repression, and DOUBLE-TIME, which plays a key role in phasing clock protein oscillations. In the same years, the Hall and Rosbash labs isolated CLOCK and CYCLE, which encode the activators of the feedback loop as well as CRYPTOCHROME, a major player for clock synchronization by light in Drosophila.
Importantly, the feedback loop mechanism is conserved in virtually all animal species and the mammalian orthologs of the period, clock, cycle and double-time genes play a similar function. Mutations in some of the human genes are involved in syndromes with sleep phase abnormalities, but how the circadian and sleep pressure signals are integrated in the brain to control sleep-wake rhythms remain to be determined.
by François Rouyer