Biological Clock: Removing Protein Repressor Boosts Clock Function Interview with:

Ruifeng Cao, MD,PhD
Postdoctoral Fellow
Laboratory of Nahum Sonenberg
McGill University
Department of Biochemistry
Montreal, QC H3A 1A3, Canada What are the main findings of the study?

Answer: Circadian (~24h) timing is a fundamental biological process, underlying cellular physiology in animals, plants, fungi, and cyanobacteria.  In mammals, including humans, a circadian clock in the brain drives daily rhythms in sleep and wakefulness, feeding and metabolism, and many other essential processes. We studied how protein synthesis, which is a fundamental process underlying many biological activities, is controlled in the brain clock in mice and identified a protein that functions as a clock repressor. By removing the repressor protein, the clock function is improved. Were any of the findings unexpected?

Answer: Usually, when we remove some proteins from the body, we expect to see some functions compromised due to the lack of these proteins.  However, we were surprised to see that the mutant mice, which don’t have the repressor protein in their clocks, exhibited enhanced clock function.  For example, by inducing a state like jet lag in these mice, we found that they were able to adapt to time zones changes in about half of the time required by normal mice. What should clinicians and patients take away from your report?

Answer: Our findings suggest that the function of the brain clock can be boosted by decreasing the activity of a specific repressor protein. This discovery could lead to the development of more effective agents to treat clock-related disorders, including jet lag, sleep disorders, shift work disorders, and chronic conditions like depression and Parkinson’s disease. What recommendations do you have for future research as a result of this study?

Answer: The obstacle to translate the current finding from bench to bedside is lack of a pharmacological agent that can inhibit the clock repressor specifically in the clock or more broadly, in the brain.  Large scale screening of small chemical compounds targeting the repressor may facilitate discovery of “tonics” for the brain clock in the future.


Translational Control of Entrainment and Synchrony of the Suprachiasmatic Circadian Clock by mTOR/4E-BP1 Signaling
79(4) pp. 712 – 724; Ruifeng Cao, Barry Robinson, Haiyan Xu, Christos Gkogkas, Arkady Khoutorsky, Tommy Alain, Akiko Yanagiya, Tatiana Nevarko, Andrew C. Liu, Shimon Amir et al.

Last Updated on April 14, 2014 by Marie Benz MD FAAD