Additional gene discovered that starts biological alarm clock

Researchers at the Salk Institute for Biological Studies, McGill University and Albert Einstein College of Medicine 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 and 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.

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.

Scientists already knew that two genes served as the key drivers for increasing PER protein levels during the day, reaching its peak around evening. However, high PER levels in the evening inhibit these two genes and it thereby reduces its own level during night. These falling PER protein levels at night causes our biological systems to slow: blood pressure drops, heart rate slows and mental processes wind down. However, until now, it was unknown what caused PER protein levels to increase again each morning.

In a report published in the September edition of Science, Satchindananda Panda and colleagues identified a type of enzyme called JARID1a, as the molecular alarm call for cells and organs to get back to work each morning

Human and mouse cells were genetically modified to under-produce JARID1a: in these cells 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.

To support their findings about the clock's workings, the researchers studied genetically altered mice cells and fruit flies that lacked the JARID1a gene. They inserted JARID1a into the flies' DNA, which and the flies returned to a normal cycle. They treated mouse cells with a drug that mimics JARID1a and this allowed their biological clocks to operate normally.

Now that scientists understand why we wake each day, they can explore the role of JARID1a in sleep disorders and chronic diseases, possibly using it as a target for new drugs.