Sriram K, Gopinathan M S
Theoretical Chemistry Group, Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036, India.
J Theor Biol. 2004 Nov 7;231(1):23-38. doi: 10.1016/j.jtbi.2004.04.006.
A two variable model with delay in both the variables, is proposed for the circadian oscillations of protein concentrations in the fungal species Neurospora crassa. The dynamical variables chosen are the concentrations of FRQ and WC-1 proteins. Our model is a two variable simplification of the detailed model of Smolen et al. (J. Neurosci. 21 (2001) 6644) modeling circadian oscillations with interlocking positive and negative feedback loops, containing 23 variables. In our model, as in the case of Smolen's model, a sustained limit cycle oscillation takes place in both FRQ and WC-1 protein in continuous darkness, and WC-1 is anti-phase to FRQ protein, as observed in experiments. The model accounts for various characteristic features of circadian rhythms such as entrainment to light dark cycles, phase response curves and robustness to parameter variation and molecular fluctuations. Simulations are carried out to study the effect of periodic forcing of circadian oscillations by light-dark cycles. The periodic forcing resulted in a rich bifurcation diagram that includes quasiperiodicity and chaotic oscillations, depending on the magnitude of the periodic changes in the light controlled parameter. When positive feedback is eliminated, our model reduces to the generic one dimensional delay model of Lema et al. (J. Theor. Biol. 204 (2000) 565), delay model of the circadian pace maker with FRQ protein as the dynamical variable which represses its own production. This one-dimensional model also exhibits all characteristic features of circadian oscillations and gives rise to circadian oscillations which are reasonably robust to parameter variations and molecular noise.
针对真菌粗糙脉孢菌中蛋白质浓度的昼夜节律振荡,提出了一个双变量且两个变量均具有延迟的模型。所选择的动力学变量是FRQ和WC - 1蛋白的浓度。我们的模型是Smolen等人(《神经科学杂志》21 (2001) 6644)详细模型的双变量简化形式,该详细模型通过相互关联的正负反馈回路对昼夜节律振荡进行建模,包含23个变量。在我们的模型中,如同Smolen的模型一样,在持续黑暗中,FRQ和WC - 1蛋白均会发生持续的极限环振荡,并且WC - 1与FRQ蛋白呈反相,这与实验观察结果一致。该模型解释了昼夜节律的各种特征,如对明暗周期的同步、相位响应曲线以及对参数变化和分子波动的鲁棒性。进行了模拟以研究明暗周期对昼夜节律振荡的周期性强迫作用的影响。周期性强迫导致了一个丰富的分岔图,该分岔图包括准周期性和混沌振荡,这取决于光控参数的周期性变化幅度。当消除正反馈时,我们的模型简化为Lema等人(《理论生物学杂志》204 (2000) 565)的一般一维延迟模型,即以FRQ蛋白作为动力学变量抑制自身产生的昼夜节律起搏器的延迟模型。这个一维模型也展现出昼夜节律振荡的所有特征,并产生对参数变化和分子噪声具有合理鲁棒性的昼夜节律振荡。