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Circadian phase resetting via single and multiple control targets.

Bagheri N, Stelling J, Doyle FJ - PLoS Comput. Biol. (2008)

Bottom Line: Circadian entrainment is necessary for rhythmic physiological functions to be appropriately timed over the 24-hour day.These studies prove the efficacy and immediate application of model predictive control in experimental studies and medicine.In particular, maintaining proper circadian regulation may significantly decrease the chance of acquiring chronic illness.

View Article: PubMed Central - PubMed

Affiliation: Department of Electrical and Computer Engineering, University of California Santa Barbara, Santa Barbara, California, USA.

ABSTRACT
Circadian entrainment is necessary for rhythmic physiological functions to be appropriately timed over the 24-hour day. Disruption of circadian rhythms has been associated with sleep and neuro-behavioral impairments as well as cancer. To date, light is widely accepted to be the most powerful circadian synchronizer, motivating its use as a key control input for phase resetting. Through sensitivity analysis, we identify additional control targets whose individual and simultaneous manipulation (via a model predictive control algorithm) out-perform the open-loop light-based phase recovery dynamics by nearly 3-fold. We further demonstrate the robustness of phase resetting by synchronizing short- and long-period mutant phenotypes to the 24-hour environment; the control algorithm is robust in the presence of model mismatch. These studies prove the efficacy and immediate application of model predictive control in experimental studies and medicine. In particular, maintaining proper circadian regulation may significantly decrease the chance of acquiring chronic illness.

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Related in: MedlinePlus

Circadian phase response behavior.Phase response curves traditionally characterize the light pulse to induced phase mapping of the input admitted to a free-running circadian oscillator. Here, phase response dynamics of the four system parameters exhibiting greatest state sensitivity is depicted: νs (mRNA transcription), νm (mRNA degradation), ks (protein translation), and νd (protein degradation). The x-axis denotes the time at which the 2 hour pulse is given (where CT0 reflects dawn and CT12 dusk), and the y-axis describes the induced phase shift. A positive shift reflects a phase advance. Since light targets TIM specific protein degradation, νdT, the light-based PRC of the Drosophila model is represented via the dash-dotted line.
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pcbi-1000104-g001: Circadian phase response behavior.Phase response curves traditionally characterize the light pulse to induced phase mapping of the input admitted to a free-running circadian oscillator. Here, phase response dynamics of the four system parameters exhibiting greatest state sensitivity is depicted: νs (mRNA transcription), νm (mRNA degradation), ks (protein translation), and νd (protein degradation). The x-axis denotes the time at which the 2 hour pulse is given (where CT0 reflects dawn and CT12 dusk), and the y-axis describes the induced phase shift. A positive shift reflects a phase advance. Since light targets TIM specific protein degradation, νdT, the light-based PRC of the Drosophila model is represented via the dash-dotted line.

Mentions: The phase response of this model as a function of light is shown via the dash-dotted line in Figure 1. This curve maps the circadian time of the entraining stimulus (light pulses) against the resulting change in phase of an organism kept in a free-running environment. The circadian time index repeats every 24 hours with CT0 defining the commencement of dawn and CT12 that of dusk. It is important to note that the magnitude of light-induced phase changes (the quantitative dynamics of the PRC) may vary with respect to the intensity of light. While this model does not account for the complexity of the real network that, for instance, includes additional positive feedback loops [14],[15], it has been experimentally validated [15] and is widely employed as a reference model [3],[16].


Circadian phase resetting via single and multiple control targets.

Bagheri N, Stelling J, Doyle FJ - PLoS Comput. Biol. (2008)

Circadian phase response behavior.Phase response curves traditionally characterize the light pulse to induced phase mapping of the input admitted to a free-running circadian oscillator. Here, phase response dynamics of the four system parameters exhibiting greatest state sensitivity is depicted: νs (mRNA transcription), νm (mRNA degradation), ks (protein translation), and νd (protein degradation). The x-axis denotes the time at which the 2 hour pulse is given (where CT0 reflects dawn and CT12 dusk), and the y-axis describes the induced phase shift. A positive shift reflects a phase advance. Since light targets TIM specific protein degradation, νdT, the light-based PRC of the Drosophila model is represented via the dash-dotted line.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2536509&req=5

pcbi-1000104-g001: Circadian phase response behavior.Phase response curves traditionally characterize the light pulse to induced phase mapping of the input admitted to a free-running circadian oscillator. Here, phase response dynamics of the four system parameters exhibiting greatest state sensitivity is depicted: νs (mRNA transcription), νm (mRNA degradation), ks (protein translation), and νd (protein degradation). The x-axis denotes the time at which the 2 hour pulse is given (where CT0 reflects dawn and CT12 dusk), and the y-axis describes the induced phase shift. A positive shift reflects a phase advance. Since light targets TIM specific protein degradation, νdT, the light-based PRC of the Drosophila model is represented via the dash-dotted line.
Mentions: The phase response of this model as a function of light is shown via the dash-dotted line in Figure 1. This curve maps the circadian time of the entraining stimulus (light pulses) against the resulting change in phase of an organism kept in a free-running environment. The circadian time index repeats every 24 hours with CT0 defining the commencement of dawn and CT12 that of dusk. It is important to note that the magnitude of light-induced phase changes (the quantitative dynamics of the PRC) may vary with respect to the intensity of light. While this model does not account for the complexity of the real network that, for instance, includes additional positive feedback loops [14],[15], it has been experimentally validated [15] and is widely employed as a reference model [3],[16].

Bottom Line: Circadian entrainment is necessary for rhythmic physiological functions to be appropriately timed over the 24-hour day.These studies prove the efficacy and immediate application of model predictive control in experimental studies and medicine.In particular, maintaining proper circadian regulation may significantly decrease the chance of acquiring chronic illness.

View Article: PubMed Central - PubMed

Affiliation: Department of Electrical and Computer Engineering, University of California Santa Barbara, Santa Barbara, California, USA.

ABSTRACT
Circadian entrainment is necessary for rhythmic physiological functions to be appropriately timed over the 24-hour day. Disruption of circadian rhythms has been associated with sleep and neuro-behavioral impairments as well as cancer. To date, light is widely accepted to be the most powerful circadian synchronizer, motivating its use as a key control input for phase resetting. Through sensitivity analysis, we identify additional control targets whose individual and simultaneous manipulation (via a model predictive control algorithm) out-perform the open-loop light-based phase recovery dynamics by nearly 3-fold. We further demonstrate the robustness of phase resetting by synchronizing short- and long-period mutant phenotypes to the 24-hour environment; the control algorithm is robust in the presence of model mismatch. These studies prove the efficacy and immediate application of model predictive control in experimental studies and medicine. In particular, maintaining proper circadian regulation may significantly decrease the chance of acquiring chronic illness.

Show MeSH
Related in: MedlinePlus