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Regulating Mechanisms of the Biological Clock to Help Those with Sleep Disorders

Study by Duke-NUS Medical School discovers the role PER2 protein plays as a central mechanism controlling the speed of the circadian clock.

An individual’s internal clock, also known as the biological clock is composed of specific proteins called clock proteins. Biological clocks are responsible for the regulation of the circadian rhythm – the process that regulates the sleep-wake cycle. Unlocking the mysteries to the molecular mechanisms of the circadian rhythm will provide potential therapeutic targets for intervention to mitigate circadian disruption. Long-term disruptions can result in chronic illnesses such as diabetes, obesity, and cancer.

In the study published in PNAS, the team used preclinical models to validate that mutations in PER2 protein can alter the balance of the circadian period, leading to sleep disorders.

Scientists from Duke-NUS had in an earlier study discovered that mutations in a protein called casein kinase 1 altered the core clock protein, PER, which in turn changed the timing of the biological clock. In the present study, preclinical models were used to investigate the role of PER2 protein in clock regulation to further strengthen the understanding.

“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,” said Dr Rajesh Narasimamurthy, Principal Research Scientist at the Duke-NUS’ Cancer and Stem Cell Biology (CSCB) programme.

“People’s sleep/wake patterns play a significant role in determining their cognitive skills, social behavior and their responses to drug,” said Professor David Virshup, Director of the Duke-NUS’ CSCB programme 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,” Prof Virshup added.

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