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Gen Kurosawa

Publications and source records attributed to Gen Kurosawa.

6 recordsLinked to original sources
PubMed2006

A model for the circadian rhythm of cyanobacteria that maintains oscillation without gene expression.

An intriguing property of the cyanobacterial circadian clock is that endogenous rhythm persists when protein abundances are kept constant either in the presence of translation and transcription inhibitors or in the constant dark condition. Here we propose a regulatory mechanism of KaiC phosphorylation for the generation of circadian oscillations in cyanobacteria. In the model, clock proteins KaiA and KaiB are assumed to have multiple states, regulating the KaiC phosphorylation process. The model can explain 1), the sustained oscillation of gene expression and protein abundance when the expression of the kaiBC gene is regulated by KaiC protein, and 2), the sustained oscillation of phosphorylated KaiC when transcription and translation processes are inhibited and total protein abundance is fixed. Results of this work suggest that KaiA and KaiB strengthen the nonlinearity of KaiC phosphorylation, thereby promoting the circadian rhythm in cyanobacteria.

Bacterial Proteins↗
PubMed2006

Amplitude of circadian oscillations entrained by 24-h light-dark cycles.

An intriguing property of circadian clocks is that their free-running period is not exactly 24h. Using models for circadian rhythms in Neurospora and Drosophila, we determine how the entrainment of these rhythms is affected by the free-running period and by the amplitude of the external light-dark cycle. We first consider the model for Neurospora, in which light acts by inducing the expression of a clock gene. We show that the amplitude of the oscillations of the clock protein entrained by light-dark cycles is maximized when the free-running period is smaller than 24h. Moreover, if the amplitude of the light-dark cycle is very strong, complex oscillations occur when the free-running period is close to 24h. In the model for circadian rhythms in Drosophila, light acts by enhancing the degradation of a clock protein. We show that while the amplitude of circadian oscillations entrained by light-dark cycles is also maximized if the free-running period is smaller than 24h, the range of entrainment is centered around 24h in this model. We discuss the physiological relevance of these results in regard to the setting of the free-running period of the circadian clock.

Animals↗
PubMed2004

Temperature compensation in circadian clock models.

Circadian clock of organisms has a free-running period that does not change much with ambient temperature. This property "temperature compensation" is studied when the rate of all reaction steps increase with temperature in the biochemical network generating the rhythm. The period becomes shorter when all the rate parameters are enhanced by the same factor. However, the period becomes longer as degradation rate of proteins and/or transcription rate of the clock gene increase (their elasticity is positive). This holds for a wide range of models, including N-variable model, and PER-TIM double oscillator model, provided that (1) branch reactions (e.g. degradation of proteins or mRNAs) are strongly saturated, and that (2) the cooperativity of transcription inhibition by nuclear proteins is not very large. A strong temperature sensitivity of degradation of PER proteins and/or temperature-sensitive alternative splicing of per gene, known for Drosophila, can be mechanisms for the temperature compensation of circadian clock.

Alternative Splicing↗
PubMed2002

Comparative study of circadian clock models, in search of processes promoting oscillation.

We study simple models for circadian rhythm, and examine the condition in which the equilibrium is unstable, generating a sustained oscillation. In the models, a clock gene(s) is transcribed to produce mRNAs, which are translated to produce proteins that suppress the transcription of the clock gene(s). First, using a Lyapunov function, we prove under very general conditions that two-variable models cannot generate a stable oscillation, implying that additional structures are needed for the model to generate a sustainable rhythm. By comparing several models of different complexities using the Routh-Hurwitz criteria of stability, we show that a sustained oscillation is more likely to occur if the cell is compartmentalized and the proteins need to be transported from the cytosol to the nucleus, if the proteins have to be modified before entering the nucleus, if the kinetics of transcription inhibition or the transport to the nucleus have cooperativity with a nonlinear dependence on the substrate concentration, or if the products of two clock genes form a heterodimer that suppresses both of their own genes. We discuss the implications of these results.

Animals↗
PubMed2002

Saturation of enzyme kinetics in circadian clock models.

From the mathematical study of simple models for circadian rhythm, the authors identified a clear effect of saturation in the enzyme kinetics on the promotion or suppression of a sustained oscillation. In the models, a clock gene (per gene) is transcribed to produce mRNAs, which are translated to produce proteins in the cytosol which are then transported to the nucleus and suppress the transcription of the gene. The negative feedback loop with a long time delay creates sustained oscillation. All the enzymatic reactions (e.g., degradation, translation, and modification) are assumed to be of Michaelis-Menten type. The reaction rate increases with the amount of substrate but saturates when it is very large. The authors prove mathematically that the saturation in any of the reactions included in the feedback loop (in-loop reaction steps) suppresses the oscillation, whereas the saturation of both degradation steps and the back transport of the protein to cytosol (branch reaction steps) makes the oscillation more likely to occur. In the experimental measurements of enzyme kinetics and in published circadian clock simulators, in-loop reaction steps have a small saturation index whereas branch reaction steps have a large saturation index.

Animals↗