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7 Publications visible to you, out of a total of 7

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Abstract The response of oscillatory systems to external perturbations is crucial for emergent properties such as synchronisation and phase locking and can be quantified in a phase response curve (PRC).hase response curve (PRC). In individual, oscillating yeast cells, we characterised experimentally the phase response of glycolytic oscillations for external acetaldehyde pulses and followed the transduction of the perturbation through the system. Subsequently, we analysed the control of the relevant system components in a detailed mechanistic model. The observed responses are interpreted in terms of the functional coupling and regulation in the reaction network. We find that our model quantitatively predicts the phase-dependent phase shift observed in the experimental data. The phase shift is in agreement with an adaptation leading to synchronisation with an external signal. Our model analysis establishes that phosphofructokinase plays a key role in the phase shift dynamics as shown in the PRC and adaptation time to external perturbations. Specific mechanism-based interventions, made possible through such analyses of detailed models, can improve upon standard trial and error methods, e.g. melatonin supplementation to overcome jet-lag, which are error-prone, specifically, since the effects are phase dependent and dose dependent. The models by Gustavsson and Goldbeter discussed in the text can be obtained from the JWS Online simulation database: (https://jjj.bio.vu.nl/models/gustavsson5 and https://jjj.bio.vu.nl/models/goldbeter1)

Authors: David D. van Niekerk, Anna-Karin Gustavsson, Martin Mojica-Benavides, Caroline B. Adiels, Mattias Goksör, Jacky L. Snoep

Date Published: 31st Jan 2019

Publication Type: Journal

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Cell signaling, gene expression, and metabolism are affected by cell-cell heterogeneity and random changes in the environment. The effects of such fluctuations on cell signaling and gene expression have recently been studied intensively using single-cell experiments. In metabolism heterogeneity may be particularly important because it may affect synchronisation of metabolic oscillations, an important example of cell-cell communication. This synchronisation is notoriously difficult to describe theoretically as the example of glycolytic oscillations shows: neither is the mechanism of glycolytic synchronisation understood nor the role of cell-cell heterogeneity. To pin down the mechanism and to assess its robustness and universality we have experimentally investigated the entrainment of glycolytic oscillations in individual yeast cells by periodic external perturbations. We find that oscillatory cells synchronise through phase shifts and that the mechanism is insensitive to cell heterogeneity (robustness) and similar for different types of external perturbations (universality).

Authors: Anna-Karin Gustavsson, Caroline B. Adiels, Bernhard Mehlig, Mattias Goksör

Date Published: 1st Aug 2015

Publication Type: Not specified

Abstract

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Authors: Anna-Karin Gustavsson, David D. van Niekerk, Caroline B. Adiels, Bob Kooi, Mattias Goksör, Jacky L. Snoep

Date Published: 1st Jun 2014

Publication Type: Not specified

Abstract

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Authors: Anna-Karin Gustavsson, David D. van Niekerk, Caroline B. Adiels, Mattias Goksör, Jacky L. Snoep

Date Published: 3rd Jan 2014

Publication Type: Not specified

Abstract

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Authors: Anna-Karin Gustavsson, David D. van Niekerk, Caroline B. Adiels, Franco B. du Preez, Mattias Goksör, Jacky L. Snoep

Date Published: 1st Aug 2012

Publication Type: Not specified

Abstract (Expand)

UNLABELLED: In an accompanying paper [du Preez et al., (2012) FEBS J279, 2810-2822], we adapt an existing kinetic model for steady-state yeast glycolysis to simulate limit-cycle oscillations. Here we validate the model by testing its capacity to simulate a wide range of experiments on dynamics of yeast glycolysis. In addition to its description of the oscillations of glycolytic intermediates in intact cells and the rapid synchronization observed when mixing out-of-phase oscillatory cell populations (see accompanying paper), the model was able to predict the Hopf bifurcation diagram with glucose as the bifurcation parameter (and one of the bifurcation points with cyanide as the bifurcation parameter), the glucose- and acetaldehyde-driven forced oscillations, glucose and acetaldehyde quenching, and cell-free extract oscillations (including complex oscillations and mixed-mode oscillations). Thus, the model was compliant, at least qualitatively, with the majority of available experimental data for glycolytic oscillations in yeast. To our knowledge, this is the first time that a model for yeast glycolysis has been tested against such a wide variety of independent data sets. DATABASE: The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.biochem.sun.ac.za/database/dupreez/index.html.

Authors: F. B. du Preez, D. D. van Niekerk, J. L. Snoep

Date Published: No date defined

Publication Type: Not specified

Abstract (Expand)

UNLABELLED: An existing detailed kinetic model for the steady-state behavior of yeast glycolysis was tested for its ability to simulate dynamic behavior. Using a small subset of experimental data, the original model was adapted by adjusting its parameter values in three optimization steps. Only small adaptations to the original model were required for realistic simulation of experimental data for limit-cycle oscillations. The greatest changes were required for parameter values for the phosphofructokinase reaction. The importance of ATP for the oscillatory mechanism and NAD(H) for inter-and intra-cellular communications and synchronization was evident in the optimization steps and simulation experiments. In an accompanying paper [du Preez F et al. (2012) FEBS J279, 2823-2836], we validate the model for a wide variety of experiments on oscillatory yeast cells. The results are important for re-use of detailed kinetic models in modular modeling approaches and for approaches such as that used in the Silicon Cell initiative. DATABASE: The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.biochem.sun.ac.za/database/dupreez/index.html.

Authors: F. B. du Preez, D. D. van Niekerk, B. Kooi, J. M. Rohwer, J. L. Snoep

Date Published: No date defined

Publication Type: Not specified

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