Goldbeter, 1995

Model Status

This model has been curated and is known to reproduce 5/6 traces from Figure 2 of the publication in PCEnv and COR; the peaks values for the Pt trace are too high.

Model Structure

Studies of the period (per) gene in Drosophila have led to a better understanding of the molecular mechanisms underlying circadian rhythms. The PER protein shares characteristics with some transcription factors, which suggests how PER can regulate the periodic expression of several other genes. per mRNA varies on a circadian cycle, and PER protein also cycles in a circadian manner, but with a several hour delay after the mRNA cycle. This suggests that the mechanism of circadian oscillations involves a negative feedback of the PER protein on transcription of the per gene. Post-translational phosphorylation of the PER protein appears to be involved in the regulation of the oscillations, as PER is phosphorylated in a circadian manner.

In the publication described here, Albert Goldbeter presents a mathematical model for circadian oscillations in the Drosophila PER protein and its mRNA. The model is based on the multiple phosphorylation of PER and on the inhibition of per transcription by a phosphorylated version of the protein (see the figure below). Model simulations support the idea that multiple PER phosphorylation introduces time delays which reinforce the capability of negative feedback to produce oscillations.

The principal prediction from the model is that there are two different ways in which calcium waves propagate in acinar cells: at low agonist concentration the wave is propagated by the diffusion of Ca²⁺ between release sites. At higher agonist concentrations the basal region of the cell responds later than the apical region, creating a wave which is independent of Ca²⁺ diffusion.

The complete original paper reference is cited below:

A Model for Circadian Oscillations in the Drosophila Period Protein (PER), Albert Goldbeter, 1995, Proceedings of the Royal Society of London, Series B, Biological Sciences , 261, 319-324. (A PDF version of the article is available on the Proceedings of the Royal Society of London, Series B, Biological Sciences website.) PubMed ID: 8587874

Scheme of the model for circadian oscillations in PER protein and per mRNA.