Modeling circadian clocks: Roles, advantages, and limitations

2011 ◽  
Vol 6 (5) ◽  
pp. 712-729 ◽  
Author(s):  
Didier Gonze
Keyword(s):  
Temperature Compensation ◽  
Molecular Level ◽  
Dynamic Properties ◽  
Biological Rhythms ◽  
Feedback Loops ◽  
Circadian Clocks ◽  
Light Pulses ◽  
Molecular Noise ◽  
Molecular Regulatory Mechanisms ◽  
Molecular Circuitry

AbstractCircadian rhythms are endogenous oscillations characterized by a period of about 24h. They constitute the biological rhythms with the longest period known to be generated at the molecular level. The abundance of genetic information and the complexity of the molecular circuitry make circadian clocks a system of choice for theoretical studies. Many mathematical models have been proposed to understand the molecular regulatory mechanisms that underly these circadian oscillations and to account for their dynamic properties (temperature compensation, entrainment by light dark cycles, phase shifts by light pulses, rhythm splitting, robustness to molecular noise, intercellular synchronization). The roles and advantages of modeling are discussed and illustrated using a variety of selected examples. This survey will lead to the proposal of an integrated view of the circadian system in which various aspects (interlocked feedback loops, inter-cellular coupling, and stochasticity) should be considered together to understand the design and the dynamics of circadian clocks. Some limitations of these models are commented and challenges for the future identified.

scholarly journals A robust and self-sustained peripheral circadian oscillator reveals differences in temperature compensation properties with central brain clocks

2020 ◽  
Author(s):  
Marijke Versteven ◽  
Karla-Marlen Ernst ◽  
Ralf Stanewsky
Keyword(s):  
Temperature Compensation ◽  
Biological Rhythms ◽  
The Body ◽  
Circadian Clocks ◽  
Luciferase Reporter ◽  
Pigment Dispersing Factor ◽  
Peripheral Oscillators ◽  
Peripheral Clocks ◽  
Central Clock ◽  
Fitness And Health

AbstractCircadian clocks temporally organize physiology and behavior of organisms exposed to the daily changes of light and temperature on our planet, thereby contributing to fitness and health. Circadian clocks and the biological rhythms they control are characterized by three properties. (1) The rhythms are self-sustained in constant conditions with a period of ~ 24 hr, (2), they can be synchronized to the environmental cycles of light and temperature, and (3), they are temperature compensated, meaning they run with the same speed at different temperatures within the physiological range of the organism. Apart from the central clocks located in or near the brain, which regulate the daily activity rhythms of animals, the so-called peripheral clocks are dispersed throughout the body of insects and vertebrates. Based on the three defining properties, it has been difficult to determine if these peripheral clocks are true circadian clocks. We used a set of clock gene – luciferase reporter genes to address this question in Drosophila circadian clocks. We show that self-sustained fly peripheral oscillators over compensate temperature changes, i.e., they slow down with increasing temperature. This over-compensation is not observed in central clock neurons in the fly brain, both in intact flies and in cultured brains, suggesting that neural network properties contribute to temperature compensation. However, an important neuropeptide for synchronizing the circadian neuronal network, the Pigment Dispersing Factor (PDF), is not required for self-sustained and temperature-compensated oscillations in subsets of the central clock neurons. Our findings reveal a fundamental difference between central and peripheral clocks, which likely also applies for vertebrate clocks.

scholarly journals A circadian clock in a nonphotosynthetic prokaryote

2021 ◽  
Vol 7 (2) ◽  
pp. eabe2086
Author(s):  
Zheng Eelderink-Chen ◽  
Jasper Bosman ◽  
Francesca Sartor ◽  
Antony N. Dodd ◽  
Ákos T. Kovács ◽  
...  
Keyword(s):  
Temperature Compensation ◽  
Temporal Structure ◽  
Bacterial Biofilm ◽  
Circadian Clocks ◽  
Industrial Processes ◽  
Free Living ◽  
Considerable Potential ◽  
Free Running ◽  
Free Running Period ◽  
Constant Dark

Circadian clocks create a 24-hour temporal structure, which allows organisms to occupy a niche formed by time rather than space. They are pervasive throughout nature, yet they remain unexpectedly unexplored and uncharacterized in nonphotosynthetic bacteria. Here, we identify in Bacillus subtilis circadian rhythms sharing the canonical properties of circadian clocks: free-running period, entrainment, and temperature compensation. We show that gene expression in B. subtilis can be synchronized in 24-hour light or temperature cycles and exhibit phase-specific characteristics of entrainment. Upon release to constant dark and temperature conditions, bacterial biofilm populations have temperature-compensated free-running oscillations with a period close to 24 hours. Our work opens the field of circadian clocks in the free-living, nonphotosynthetic prokaryotes, bringing considerable potential for impact upon biomedicine, ecology, and industrial processes.

scholarly journals Genetic interactions between clock mutations in Neurospora crassa : can they help us to understand complexity?

2001 ◽  
Vol 356 (1415) ◽  
pp. 1717-1724 ◽  
Author(s):  
Louis W. Morgan ◽  
Jerry F. Feldman ◽  
Deborah Bell-Pedersen
Keyword(s):  
Coupled Oscillators ◽  
Temperature Compensation ◽  
White Collar ◽  
Circadian System ◽  
Genetic Interactions ◽  
Circadian Clocks ◽  
Metabolic Effects ◽  
Clock Model ◽  
Number Of Genes ◽  
Single Oscillator

Recent work on circadian clocks in Neurospora has primarily focused on the frequency ( frq ) and white–collar ( wc ) loci. However, a number of other genes are known that affect either the period or temperature compensation of the rhythm. These include the period (no relationship to the period gene of Drosophila ) genes and a number of genes that affect cellular metabolism. How these other loci fit into the circadian system is not known, and metabolic effects on the clock are typically not considered in single–oscillator models. Recent evidence has pointed to multiple oscillators in Neurospora , at least one of which is predicted to incorporate metabolic processes. Here, the Neurospora clock–affecting mutations will be reviewed and their genetic interactions discussed in the context of a more complex clock model involving two coupled oscillators: a FRQ/WC–based oscillator and a ‘ frq –less’ oscillator that may involve metabolic components.

Effect of somatostatin on circadian rhythms of firing and 2-deoxyglucose uptake in rat suprachiasmatic slices

1993 ◽  
Vol 265 (5) ◽  
pp. R1199-R1204 ◽  
Author(s):  
T. Hamada ◽  
S. Shibata ◽  
A. Tsuneyoshi ◽  
K. Tominaga ◽  
S. Watanabe
Keyword(s):  
Circadian Rhythm ◽  
Vasoactive Intestinal Polypeptide ◽  
Phase Changes ◽  
Circadian Clocks ◽  
Constant Darkness ◽  
Phase Resetting ◽  
Firing Activity ◽  
Light Pulses ◽  
Circadian Time

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus appears to act as a circadian clock. The SCN vasoactive intestinal polypeptide-like immunoreactive neurons, which may act to mediate photic information in the SCN, receive input from neurons immunoreactive for somatostatin (SST). Therefore we investigated the role of SST as a transmitter for entrainment by analyzing the phase-resetting effect of SST on the circadian rhythm of SCN firing activity. Perfusion of SST increased 2-deoxyglucose uptake at circadian time (CT) 18, but not at CT6. A 1-h or 15-min treatment with SST produced phase delays when it was administered at CT13-14 and phase advances at CT22-23. Thus SST-induced phase changes are similar to those for light pulses to animals under constant darkness. The present findings suggest that SST is a transmitter for mediating information of entrainment to circadian clocks within the SCN.

scholarly journals Digital signaling network drives the assembly of the AIM2-ASC inflammasome

2018 ◽  
Vol 115 (9) ◽  
pp. E1963-E1972 ◽  
Author(s):  
Mariusz Matyszewski ◽  
Seamus R. Morrone ◽  
Jungsan Sohn
Keyword(s):  
Host Defense ◽  
Positive Feedback ◽  
Signal Amplification ◽  
Molecular Level ◽  
Design Principles ◽  
Digital Circuit ◽  
Quantitative Model ◽  
Feedback Loops ◽  
Signaling Network

The AIM2-ASC inflammasome is a filamentous signaling platform essential for mounting host defense against cytoplasmic dsDNA arising not only from invading pathogens but also from damaged organelles. Currently, the design principles of its underlying signaling network remain poorly understood at the molecular level. We show here that longer dsDNA is more effective in inducing AIM2 assembly, its self-propagation, and downstream ASC polymerization. This observation is related to the increased probability of forming the base of AIM2 filaments, and indicates that the assembly discerns small dsDNA as noise at each signaling step. Filaments assembled by receptor AIM2, downstream ASC, and their joint complex all persist regardless of dsDNA, consequently generating sustained signal amplification and hysteresis. Furthermore, multiple positive feedback loops reinforce the assembly, as AIM2 and ASC filaments accelerate the assembly of nascent AIM2 with or without dsDNA. Together with a quantitative model of the assembly, our results indicate that an ultrasensitive digital circuit drives the assembly of the AIM2-ASC inflammasome.

scholarly journals Genetic variation and phenotypic plasticity in circadian rhythms in an armed beetle, Gnatocerus cornutus (Tenebrionidae)

2020 ◽  
Vol 130 (1) ◽  
pp. 34-40 ◽  
Author(s):  
Kentarou Matsumura ◽  
Masato S Abe ◽  
Manmohan D Sharma ◽  
David J Hosken ◽  
Taishi Yoshii ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Phenotypic Plasticity ◽  
Circadian Rhythms ◽  
Temperature Effects ◽  
Temperature Compensation ◽  
Biological Rhythms ◽  
Total Activity ◽  
Biological Clocks ◽  
Isofemale Lines ◽  
Free Running

Abstract Circadian rhythms, their free-running periods and the power of the rhythms are often used as indicators of biological clocks, and there is evidence that the free-running periods of circadian rhythms are not affected by environmental factors, such as temperature. However, there are few studies of environmental effects on the power of the rhythms, and it is not clear whether temperature compensation is universal. Additionally, genetic variation and phenotypic plasticity in biological clocks are important for understanding the evolution of biological rhythms, but genetic and plastic effects are rarely investigated. Here, we used 18 isofemale lines (genotypes) of Gnatocerus cornutus to assess rhythms of locomotor activity, while also testing for temperature effects. We found that total activity and the power of the circadian rhythm were affected by interactions between sex and genotype or between sex, genotype and temperature. The males tended to be more active and showed greater increases in activity, but this effect varied across both genotypes and temperatures. The period of activity varied only by genotype and was thus independent of temperature. The complicated genotype–sex–environment interactions we recorded stress the importance of investigating circadian activity in more integrated ways.

scholarly journals Post-translational Modifications are Required for Circadian Clock Regulation in Vertebrates

2019 ◽  
Vol 20 (5) ◽  
pp. 332-339 ◽  
Author(s):  
Yoshimi Okamoto-Uchida ◽  
Junko Izawa ◽  
Akari Nishimura ◽  
Atsuhiko Hattori ◽  
Nobuo Suzuki ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Feedback Loops ◽  
Circadian Clocks ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Negative Feedback Loops ◽  
Genetic Techniques ◽  
External Signals ◽  
Exact Timing

Circadian clocks are intrinsic, time-tracking systems that bestow upon organisms a survival advantage. Under natural conditions, organisms are trained to follow a 24-h cycle under environmental time cues such as light to maximize their physiological efficiency. The exact timing of this rhythm is established via cell-autonomous oscillators called cellular clocks, which are controlled by transcription/ translation-based negative feedback loops. Studies using cell-based systems and genetic techniques have identified the molecular mechanisms that establish and maintain cellular clocks. One such mechanism, known as post-translational modification, regulates several aspects of these cellular clock components, including their stability, subcellular localization, transcriptional activity, and interaction with other proteins and signaling pathways. In addition, these mechanisms contribute to the integration of external signals into the cellular clock machinery. Here, we describe the post-translational modifications of cellular clock regulators that regulate circadian clocks in vertebrates.

scholarly journals Weak Coupling Between Intracellular Feedback Loops Explains Dissociation of Clock Gene Dynamics

2019 ◽  
Author(s):  
Christoph Schmal ◽  
Daisuke Ono ◽  
Jihwan Myung ◽  
J. Patrick Pett ◽  
Sato Honma ◽  
...  
Keyword(s):  
Single Cell ◽  
Clock Genes ◽  
Experimental Studies ◽  
Feedback Loops ◽  
Light Pulses ◽  
Negative Feedback Loops ◽  
Medium Exchange ◽  
A Cell ◽  
Free Running ◽  
Underlying Mechanisms

Circadian rhythms are generated by interlocked transcriptional-translational negative feedback loops (TTFLs), the molecular process implemented within a cell. The contributions, weighting and balancing between the multiple feedback loops remain debated. Dissociated, free-running dynamics in the expression of distinct clock genes has been described in recent experimental studies that applied various perturbations such as slice preparations, light pulses, jet-lag, and culture medium exchange. In this paper, we provide evidence that this "presumably transient" dissociation of circadian gene expression oscillations may occur at the single-cell level. Conceptual and detailed mechanistic mathematical modeling suggests that such dissociation is due to a weak interaction between multiple feedback loops present within a single cell. The dissociable loops provide insights into underlying mechanisms and general design principles of the molecular circadian clock.

scholarly journals Balance equations can buffer noisy and sustained environmental perturbations of circadian clocks

2010 ◽  
Vol 1 (1) ◽  
pp. 177-186 ◽  
Author(s):  
Mirela Domijan ◽  
David A. Rand
Keyword(s):  
Temperature Compensation ◽  
Regulatory Networks ◽  
Circadian Clocks ◽  
Balance Equations ◽  
New Approach ◽  
Environmental Perturbations ◽  
Environmental Fluctuations ◽  
Free Running ◽  
Temperature Levels

We present a new approach to understanding how regulatory networks such as circadian clocks might evolve robustness to environmental fluctuations. The approach is in terms of new balance equations that we derive. We use it to describe how an entrained clock can buffer the effects of daily fluctuations in light and temperature levels. We also use it to study a different approach to temperature compensation where instead of considering a free-running clock, we study temperature buffering of the phases in a light-entrained clock, which we believe is a more physiological setting.

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