Circadian clocks are found across all higher species, controlling daily rhythms of behaviour and physiology. The clocks are thought to tick by the continuous creation and degradation of clock proteins in a 24 hour cycle. The principle clock in humans is the suprachiasmatic nucleus (SCN) which is governed by Period genes (Per1, Per2).
Recent research by The University of Manchester and The University of Cambridge has dispelled the previous theory that in mammals Per 2 is let in to the cell nucleus by a ‘gate’ from the outer cytoplasm. Previous studies in fruit flies had shown that Per2 builds up in the cytoplasm until it reaches a critical level at which point the gate would open, allowing it to enter the nucleus.
It is this movement from cytoplasm to nucleus that dictates the tempo of the fly’s body clock.
According to Professor Andrew Loudon from The University of Manchester, this gated mechanism found in flies does not happen in mammals. Instead, the protein moves from the cytoplasm to the nucleus straight away.
Professor Loudon said:
“We have discovered that the level of the per2 builds up in the nucleus and it is this build-up of protein that gives the clock its rhythm.
This is an important advancement in our understanding of the body clock at the cellular level.
As new insights into how our body clocks function are discovered, drugs are being developed which will effectively target the mechanism responsible for circadian imbalances.
We think that this non-gated system is likely to be susceptible to drug intervention – but clearly more work is needed on that front.”
Disorders of the circadian clock, ranging from jet-lag, through shift-work to sleep disorders associated with ageing, dementia and psychiatric illness have a major impact on our health. This work went on to show how particular drugs affect the behaviour of the clock proteins and could provide a first approach to developing suitable therapeutics to treat sleep disorders.
The work was funded by the MRC and BBSRC.