Biological clocks are composed of specific proteins called clock proteins, which interact in cells throughout the body. Biological clocks produce and regulate circadian rhythms—the physical, mental, and behavioral changes that follow a daily cycle. Understanding the molecular mechanisms of the circadian clock provides a huge potential to identify therapeutic interventions to mitigate circadian disruption, and its long-term consequences such as diabetes, obesity, and cancer among shift workers, who undergo frequent circadian disruption and are more prone to these diseases.

In Singapore, Duke-NUS scientists had previously discovered that mutations in a specific protein (called casein kinase 1) alter the core clock protein (called PERIOD or PER), and this changes the timing of the biological clock. In a new study, preclinical models were used to investigate the role of PER2 (a type of PER protein) in clock regulation to further understand and strengthen the model.

“The study findings clearly demonstrated that targeted mutations in the PER2 protein can alter the balance of biological clock and can significantly lengthen the circadian period in preclinical models,” says Rajesh Narasimamurthy, PhD, principal research scientist at the Duke-NUS’ Cancer and Stem Cell Biology (CSCB) program, in a release.

“People’s sleep/wake patterns play a significant role in determining their cognitive skills, social behavior, and their responses to drug,” says David Virshup, MD, director of the Duke-NUS’ CSCB program, professor, and corresponding author of this study. “Our study helps us understand and validate the genetic and biochemical regulation of our circadian sleep/wake cycles, which can produce a morning lark or night owl effect. Understanding how the clock works can help in the development of new therapeutic interventions for treating people with sleep disorders.”

“Sleep disorders are increasingly recognised as a major public health concern. This important study by our researchers could open new possibilities and strategies to treat sleep disorders, and improve the quality of life among affected individuals in Singapore and beyond,” said Patrick Casey, PhD, professor and senior vice dean for research at Duke-NUS.

The new study is published in Proceedings of the National Academy of Sciences.

The team is currently investigating other factors that can cause mutation in PER2 protein and regulate the clock speed.