Dynamics of the Tyson-Hong-Thron-Novak circadian oscillator model (Q2077642)

Circadian rhythms of physiology and behaviour due to the 24-hour cycle of light and darkness prevalent on Earth have been found in a variety of organisms. Here, the authors study the dynamics of a model for the circadian rhythm in the fruit fly \textit{Drosophila melanogaster} which was proposed in [\textit{J. Tyson}, \textit{C. Hong}, \textit{C. Thron}, \textit{B. Novak}, Biophys. J., 77, 2411--2417 (1999)]. While classical models are formulated as high-dimensional systems of ordinary differential equations that contain negative feedback loops, the three-dimensional model considered here incorporates positive feedback on the basis of experimental observations on phosphorylation and proteolysis [\textit{B. Kloss}, \textit{J. L. Price}, \textit{L. Saez}, \textit{et al.}, Cell, 94, 97--107 (1998)], with the relevant chemical species being mRNA, protein monomer, and protein dimer. By application of a quasi-steady state approximation (QSSA), that model is then effectively reduced to the simpler two-dimensional Tyson-Hong-Thron-Novak (THTN) model. The authors consider the two scenarios where the rate of mRNA degradation in the THTN model is either high or low. In the former scenario, they prove that no biologically relevant periodic solutions exist by showing the existence of a bounded attractor; in the latter, they formulate the THTN model as a slow-fast system, which they proceed to analyse via geometric singular perturbation theory (GSPT) [\textit{G. Hek}, J. Math. Biol., 60, 347--386 (2010; Zbl 1311.34133)]. Specifically, after transformation to an equivalent normal form, they observe various phenomena that are typically associated with planar slow-fast dynamics, such as relaxation oscillation, canard explosion [\textit{M. Krupa}, \textit{P. Szmolyan}, J. Differential Equations, 174, 312--368 (2001; Zbl 0994.34032)], saddle-node bifurcation, and limit cycle behaviour. Finally, they interpret their findings from a biophysical perspective; in particular, they relate the coexistence of two limit cycles in certain parameter regimes to birhythmicity which has been postulated for circadian oscillators.