03 Oct And the Nobel prize goes to… Sleep!
The international classification of sleep disorders states that for optimal sleep, the desired sleep time should match the timing of the circadian rhythm of sleep and wake propensity. Chronic or recurrent circadian disorders may arise from alterations of the circadian timing system or a misalignment between the timing of the individual’s circadian rhythm of sleep propensity and the 24hr social and physical environments.
Hall Robash and Young have been awarded the 2017 Nobel Prize for their work on circadian rhythms. Simply put, they have significantly contributed to the understanding of circadian rhythms at a genetic level. Their findings have been quite revolutionary. Initially it was thought that circadian rhythms were controlled centrally by just one part of the brain, a neural type of clock. We now understand that each living thing may have not just one, but many different internal clocks, even beings without a neural network can have circadian rhythms. Their work has spanned nearly 30 years, often using mouse and drosophila models, their work has helped to identify and understand certain gene expressions and the significant impact these have on cell and organismal physiology
Key genes of chronobiology: CLOCK, BMAL1, Period, Timeless, Doubletime, Cryptochrome, Mef2.
Simplified overview: CLOCK and BMAL1 encode proteins that combine, and switch on Period and Cryptochrome. When Period and Cryptochrome reach a certain level they switch off CLOCK and BMAL1. This creates a cyclical pattern that lasts 24hrs. CLOCK and BMAL1 are active during the day with Period and Crytochrome active at night. As they rise and fall, this quartet of expressed genes (proteins) turn on and off many other genes throughout the body accounting for a wide range of circadian influences in the body. This work helps us understand the wide ranging effects of circadian rhythms within the body.
Some interesting findings relating to the circadian cycle:
- Influence in the liver. Not only do CLOCK and BMAL1 bind to many metabolism genes (contributing to hunger at certain times of the day), but they also recruit RNA polymerase II throughout the genome on a circadian basis – potentially influencing all gene transcription
- Circadian influence in RNA transcription and RNA translation
- Neurons in the Suprachiasmatic Nucleus (SCN) equivalent in drosophila become active and branch out, contacting many other neurons in response to light and then contract and become less active at night
- Alzheimers, depression, ADHD, heart disease & diabetes may be linked to circadian issues
- Some circadian influence on gene expression in plants (expression not light driven)
- Some cyanobacteria have circadian influences (expression not light driven)
Press release from www.nobelprize.org can be found here:
https://www.nobelprize.org/nobel_prizes/medicine/laureates/2017/press.html
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