Ever wondered why you wake up in the morning—even when the alarm clock isn’t making jarring noises?
Researchers at the Salk Institute for Biological Studies have identified a new component of the biological clock, a gene responsible for starting the clock from its restful state every morning.
The biological clock ramps up our metabolism early each day, initiating important physiological functions that tell our bodies that it’s time to rise and shine. Discovery of this new gene and the mechanism by which it starts the clock everyday may help explain the genetic underpinnings of sleeplessness, aging and chronic illnesses, such as cancer and diabetes, and could eventually lead to new therapies for these illnesses.
In a report published in September, 29 in the journal Science, the Salk researchers and their collaborators at McGill University and Albert Einstein College of Medicine describe how the gene KDM5A encodes a protein, JARID1a, that serves as an activation switch in the biochemical circuit that maintains our circadian rhythm.
The discovery fills in a missing link in the molecular mechanisms that control our daily wake-sleep cycle. The central player of our biological clock is a protein called PERIOD (PER). The number of PER proteins in each of our cells rises and falls every 24 hours. Our cells use the level of PER protein as an indicator of the time of the day and tell our body when to sleep or be awake.
As we already know about two genes CLOCK and BMAL1, served as the key drivers for raising PER protein levels. As the level of PER protein rises during the daytime, reaching its peak around evening, it somehow puts a break on CLOCK and BMAL, thereby reducing its own level during nighttime.
Falling PER protein levels at night causes our biological systems to slow: our blood pressure drops, our heart rate slows and our mental processes wind down. But, until now, the precise nature of the nighttime brake and what let CLOCK and BMAL proteins overcome this brake to raise PER protein levels again each morning was a mystery.
In their research, which was primarily funded by Salk’s Innovation Fund, Panda and his colleagues identified JARID1a, a type of enzyme, as the molecular bugle call for cells and organs to get back to work each morning. By studying the genetic mechanisms underlying circadian rhythms in human and mouse cells and in fruit flies, the researchers discovered that JARID1a was required for normal cycling, both at the cellular level and in terms of an organisms’ daily behavior.
In human and mouse cells that were genetically modified to under-produce JARID1a, the PER protein did not rise to its normal peak each day. Fruit flies that were similarly genetically altered also had low levels of PER protein. The flies lost track of time: they did not know when to sleep or wake up and took frequent naps throughout the day and night.