The Goodwin Model: Simulating the Effect of Cycloheximide and Heat Shock on the Sporulation Rhythm ofNeurospora crassa

Ruoff, Peter; Vinsjevik, Merete; Mohsenzadeh, Saadat; Rensing, Ludger

doi:10.1006/jtbi.1998.0846

Cited by 45 publications

(40 citation statements)

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“…The basic oscillator module I use is a Goodwin oscillator (45), which has been successfully used to model circadian oscillations in the fungus N. crassa. Not only can it exhibit stable circadian oscillations of an appropriate frequency, but it also correctly predicts the response of circadian rhythms to stimuli such as temperature pulses, light pulses, and an inhibitor of protein synthesis (6,32,33). In this elementary oscillator, a gene expresses a mRNA molecule R that is translated into protein P. This protein is modified, such as through dimerization or phosphorylation, to generate an inhibitor PЈ of its own expression.…”

Section: Methods and Resultsmentioning

confidence: 95%

“…For each possible circuit topology (Fig. 1a), I chose 5 ϫ 10 3 parameter combinations at random from a parameter space within which circadian oscillations are known to occur (6,32,33) for the elementary oscillator (R i , P i , P i Ј ). For each of these parameter combinations, I examined whether the circuit adopts limit cycle oscillations with a period of Ϸ24 h. Limit cycle oscillations have two features typical of circadian oscillators: they are stable to minor perturbations of regulator concentrations, and they persist over time even when the organism is not subject to periodic driving forces (e.g., light exposure) (34,47).…”

Section: Different Topologies Have a Highly Skewed Distribution Of Thmentioning

confidence: 99%

“…The focus of this contribution is such an analysis for several hundred variants of a cellular circuit model that has been successfully used to describe circadian rhythms in different organisms (6,32,33).…”

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confidence: 99%

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Circuit topology and the evolution of robustness in two-gene circadian oscillators

Wagner

2005

Proc. Natl. Acad. Sci. U.S.A.

141

122

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Many parameters driving the behavior of biochemical circuits vary extensively and are thus not fine-tuned. Therefore, the topology of such circuits (the who-interacts-with-whom) is key to understanding their central properties. I here explore several hundred different topologies of a simple biochemical model of circadian oscillations to ask two questions: Do different circuits differ dramatically in their robustness to parameter change? If so, can a process of gradual molecular evolution find highly robust topologies when starting from less robust topologies? I find that the distribution of robustness among different circuit topologies is highly skewed: Most show low robustness, whereas very few topologies are highly robust. To address the second evolutionary question, I define a topology graph, each of whose nodes corresponds to one circuit topology that shows circadian oscillations. Two nodes in this graph are connected if they differ by only one regulatory interaction within the circuit. For the circadian oscillator I study, most topologies are connected in this graph, making evolutionary transitions from low to high robustness easy. A similar approach has been used to study the evolution of robustness in biological macromolecules, with similar results. This suggests that the same principles govern the evolution of robustness on different levels of biological organization. The regulatory interlocking of several oscillating gene products in biological circadian oscillators may exist because it provides robustness. complexity ͉ gene networks

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Section: Methods and Resultsmentioning

confidence: 95%

Section: Different Topologies Have a Highly Skewed Distribution Of Thmentioning

confidence: 99%

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Circuit topology and the evolution of robustness in two-gene circadian oscillators

Wagner

2005

Proc. Natl. Acad. Sci. U.S.A.

141

122

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“…It should be noted that there is a number of alternative approaches and models for description of fungal colonies patterning [3,10,[14][15][16][17]19]. For example, concentric rings formation in Neurospora crassa is explained as a result of circadian clock functioning [5,10,19].…”

Section: Resultsmentioning

confidence: 99%

“…For example, concentric rings formation in Neurospora crassa is explained as a result of circadian clock functioning [5,10,19]. Other models also take into account the effect of toxic metabolites accumulation, which play an important role as inhibitors for cell division [14,15].…”

Section: Resultsmentioning

confidence: 99%

Fungal Colony Patterning as an Example of Biological Self-Organization

Bystrova

Богомолова

Panina

et al.

Unifying Themes in Complex Systems IV

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Modeling the molecular regulatory mechanism of circadian rhythms in Drosophila

Leloup

Goldbeter

2000

Bioessays

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Thanks to genetic and biochemical advances on the molecular mechanism of circadian rhythms in Drosophila, theoretical models closely related to experimental observations can be considered for the regulatory mechanism of the circadian clock in this organism. Modeling is based on the autoregulatory negative feedback exerted by a complex between PER and TIM proteins on the expression of per and tim genes. The model predicts the occurrence of sustained circadian oscillations in continuous darkness. When incorporating light-induced TIM degradation, the model accounts for damping of oscillations in constant light, entrainment of the rhythm by light-dark cycles of varying period or photoperiod, and phase shifting by light pulses. The model further provides a molecular dynamical explanation for the permanent or transient suppression of circadian rhythmicity triggered in a variety of organisms by a critical pulse of light. Finally, the model shows that to produce a robust rhythm the various clock genes must be expressed at the appropriate levels since sustained oscillations only occur in a precise range of parameter values. BioEssays 22:84 -93, 2000.

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The Goodwin Model: Simulating the Effect of Cycloheximide and Heat Shock on the Sporulation Rhythm ofNeurospora crassa

Cited by 45 publications

References 0 publications

Circuit topology and the evolution of robustness in two-gene circadian oscillators

Circuit topology and the evolution of robustness in two-gene circadian oscillators

Fungal Colony Patterning as an Example of Biological Self-Organization

Modeling the molecular regulatory mechanism of circadian rhythms in Drosophila

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