This animation explores the molecular interactions that regulate circadian rhythms in mammals.

Most organisms have circadian rhythms, biological processes that operate on 24-hour cycles. These rhythms are regulated by an internal timekeeping mechanism called the biological clock. The animation explores a series of cyclically expressed proteins that maintain the biological clock in mammals.

The animation begins by introducing Period (Per) and Cryptochrome (Cry), genes that are activated by the transcription factors BMAL and CLOCK. The resulting PER and CRY proteins form structures that can block the activation of BMAL and CLOCK, creating a negative feedback loop. PER and CRY proteins are eventually degraded, and the cycle begins again.

The next section of the animation introduces another protein, casein kinase 1 epsilon (CK1ε), that can accelerate the degradation of PER. The animation illustrates how a mutation in CK1ε, called the tau mutation, impairs its ability to degrade PER and ultimately lengthens the circadian period.

This animation is a clip from a 2000 Holiday Lecture Series, Clockwork Genes: Discoveries in Biological Time. Depending on students’ background, it may be helpful to pause the animation at various points to discuss different proteins or parts of the biological clock pathway.