References of "Ederer, Michael"
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See detailBasic Regulatory Principles of Escherichia coli's Electron Transport Chain for Varying Oxygen Conditions.
Henkel, Sebastian G.; Beek, Alexander Ter; Steinsiek, Sonja et al

in PloS one (2014), 9(9), 107640

For adaptation between anaerobic, micro-aerobic and aerobic conditions Escherichia coli's metabolism and in particular its electron transport chain (ETC) is highly regulated. Although it is known that the ... [more ▼]

For adaptation between anaerobic, micro-aerobic and aerobic conditions Escherichia coli's metabolism and in particular its electron transport chain (ETC) is highly regulated. Although it is known that the global transcriptional regulators FNR and ArcA are involved in oxygen response it is unclear how they interplay in the regulation of ETC enzymes under micro-aerobic chemostat conditions. Also, there are diverse results which and how quinones (oxidised/reduced, ubiquinone/other quinones) are controlling the ArcBA two-component system. In the following a mathematical model of the E. coli ETC linked to basic modules for substrate uptake, fermentation product excretion and biomass formation is introduced. The kinetic modelling focusses on regulatory principles of the ETC for varying oxygen conditions in glucose-limited continuous cultures. The model is based on the balance of electron donation (glucose) and acceptance (oxygen or other acceptors). Also, it is able to account for different chemostat conditions due to changed substrate concentrations and dilution rates. The parameter identification process is divided into an estimation and a validation step based on previously published and new experimental data. The model shows that experimentally observed, qualitatively different behaviour of the ubiquinone redox state and the ArcA activity profile in the micro-aerobic range for different experimental conditions can emerge from a single network structure. The network structure features a strong feed-forward effect from the FNR regulatory system to the ArcBA regulatory system via a common control of the dehydrogenases of the ETC. The model supports the hypothesis that ubiquinone but not ubiquinol plays a key role in determining the activity of ArcBA in a glucose-limited chemostat at micro-aerobic conditions. [less ▲]

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See detailAnalysing the role of UVB-induced translational inhibition and PP2Ac deactivation in NF-kappaB signalling using a minimal mathematical model.
Witt, Johannes; Konrath, Fabian; Sawodny, Oliver et al

in PLoS ONE (2012), 7(7), 40274

Activation of nuclear factor kappaB (NF-kappaB) by interleukin-1beta (IL-1) usually results in an anti-apoptotic activity that is rapidly terminated by a negative feedback loop involving NF-kappaB ... [more ▼]

Activation of nuclear factor kappaB (NF-kappaB) by interleukin-1beta (IL-1) usually results in an anti-apoptotic activity that is rapidly terminated by a negative feedback loop involving NF-kappaB dependent resynthesis of its own inhibitor IkappaBalpha. However, apoptosis induced by ultraviolet B radiation (UVB) is not attenuated, but significantly enhanced by co-stimulation with IL-1 in human epithelial cells. Under these conditions NF-kappaB remains constitutively active and turns into a pro-apoptotic factor by selectively repressing anti-apoptotic genes. Two different mechanisms have been separately proposed to explain UV-induced lack of IkappaBalpha recurrence: global translational inhibition as well as deactivation of the Ser/Thr phosphatase PP2Ac. Using mathematical modelling, we show that the systems behaviour requires a combination of both mechanisms, and we quantify their contribution in different settings. A mathematical model including both mechanisms is developed and fitted to various experimental data sets. A comparison of the model results and predictions with model variants lacking one of the mechanisms shows that both mechanisms are present in our experimental setting. The model is successfully validated by the prediction of independent data. Weak constitutive IKKbeta phosphorylation is shown to be a decisive process in IkappaBalpha degradation induced by UVB stimulation alone, but irrelevant for (co-)stimulations with IL-1. In silico knockout experiments show that translational inhibition is predominantly responsible for lack of IkappaBalpha recurrence following IL-1+UVB stimulation. In case of UVB stimulation alone, cooperation of both processes causes the observed decrease of IkappaBalpha. This shows that the processes leading to activation of transcription factor NF-kappaB upon stimulation with ultraviolet B radiation with and without interleukin-1 costimulation are more complex than previously thought, involving both a cross talk of UVB induced translational inhibition and PP2Ac deactivation. The importance of each of the mechanisms depends on the specific cellular setting. [less ▲]

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See detailModeling time delay in the NFkappaB signaling pathway following low dose IL-1 stimulation.
Witt, Johannes; Barisic, Sandra; Sawodny, Oliver et al

in EURASIP Journal on Bioinformatics & Systems Biology (2011), 2011(1), 3

Stimulation of human epithelial cells with IL-1 (10 ng/ml) + UVB radiation results in sustained NFkappaB activation caused by continuous IKKbeta phosphorylation. We have recently published a strictly ... [more ▼]

Stimulation of human epithelial cells with IL-1 (10 ng/ml) + UVB radiation results in sustained NFkappaB activation caused by continuous IKKbeta phosphorylation. We have recently published a strictly reduced ordinary differential equation model elucidating the involved mechanisms. Here, we compare model extensions for low IL-1 doses (0.5 ng/ml), where delayed IKKbeta phosphorylation is observed. The extended model including a positive regulatory element, most likely auto-ubiquitination of TRAF6, reproduces the observed experimental data most convincingly. The extension is shown to be consistent with the original model and contains very sensitive processes which may serve as potential intervention targets. [less ▲]

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See detailA systems biology approach to analyse leaf carbohydrate metabolism in Arabidopsis thaliana.
Henkel, Sebastian; Nagele, Thomas; Hormiller, Imke et al

in EURASIP Journal on Bioinformatics & Systems Biology (2011), 2011(1), 2

Plant carbohydrate metabolism comprises numerous metabolite interconversions, some of which form cycles of metabolite degradation and re-synthesis and are thus referred to as futile cycles. In this study ... [more ▼]

Plant carbohydrate metabolism comprises numerous metabolite interconversions, some of which form cycles of metabolite degradation and re-synthesis and are thus referred to as futile cycles. In this study, we present a systems biology approach to analyse any possible regulatory principle that operates such futile cycles based on experimental data for sucrose (Scr) cycling in photosynthetically active leaves of the model plant Arabidopsis thaliana. Kinetic parameters of enzymatic steps in Scr cycling were identified by fitting model simulations to experimental data. A statistical analysis of the kinetic parameters and calculated flux rates allowed for estimation of the variability and supported the predictability of the model. A principal component analysis of the parameter results revealed the identifiability of the model parameters. We investigated the stability properties of Scr cycling and found that feedback inhibition of enzymes catalysing metabolite interconversions at different steps of the cycle have differential influence on stability. Applying this observation to futile cycling of Scr in leaf cells points to the enzyme hexokinase as an important regulator, while the step of Scr degradation by invertases appears subordinate. [less ▲]

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See detailMathematical modeling of the central carbohydrate metabolism in Arabidopsis reveals a substantial regulatory influence of vacuolar invertase on whole plant carbon metabolism.
Nagele, Thomas; Henkel, Sebastian; Hormiller, Imke et al

in Plant Physiology (2010), 153(1), 260-72

A mathematical model representing metabolite interconversions in the central carbohydrate metabolism of Arabidopsis (Arabidopsis thaliana) was developed to simulate the diurnal dynamics of primary carbon ... [more ▼]

A mathematical model representing metabolite interconversions in the central carbohydrate metabolism of Arabidopsis (Arabidopsis thaliana) was developed to simulate the diurnal dynamics of primary carbon metabolism in a photosynthetically active plant leaf. The model groups enzymatic steps of central carbohydrate metabolism into blocks of interconverting reactions that link easily measurable quantities like CO(2) exchange and quasi-steady-state levels of soluble sugars and starch. When metabolite levels that fluctuate over diurnal cycles are used as a basic condition for simulation, turnover rates for the interconverting reactions can be calculated that approximate measured metabolite dynamics and yield kinetic parameters of interconverting reactions. We used experimental data for Arabidopsis wild-type plants, accession Columbia, and a mutant defective in vacuolar invertase, AtbetaFruct4, as input data. Reducing invertase activity to mutant levels in the wild-type model led to a correct prediction of increased sucrose levels. However, additional changes were needed to correctly simulate levels of hexoses and sugar phosphates, indicating that invertase knockout causes subsequent changes in other enzymatic parameters. Reduction of invertase activity caused a decline in photosynthesis and export of reduced carbon to associated metabolic pathways and sink organs (e.g. roots), which is in agreement with the reported contribution of vacuolar invertase to sink strength. According to model parameters, there is a role for invertase in leaves, where futile cycling of sucrose appears to have a buffering effect on the pools of sucrose, hexoses, and sugar phosphates. Our data demonstrate that modeling complex metabolic pathways is a useful tool to study the significance of single enzyme activities in complex, nonintuitive networks. [less ▲]

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See detailON/OFF and beyond--a boolean model of apoptosis.
Schlatter, Rebekka; Schmich, Kathrin; Avalos Vizcarra, Ima et al

in PLoS Computational Biology (2009), 5(12), 1000595

Apoptosis is regulated by several signaling pathways which are extensively linked by crosstalks. Boolean or logical modeling has become a promising approach to capture the qualitative behavior of such ... [more ▼]

Apoptosis is regulated by several signaling pathways which are extensively linked by crosstalks. Boolean or logical modeling has become a promising approach to capture the qualitative behavior of such complex networks. Here we built a large-scale literature-based Boolean model of the central intrinsic and extrinsic apoptosis pathways as well as pathways connected with them. The model responds to several external stimuli such as Fas ligand, TNF-alpha, UV-B irradiation, interleukin-1beta and insulin. Timescales and multi-value node logic were used and turned out to be indispensable to reproduce the behavior of the apoptotic network. The coherence of the model was experimentally validated. Thereby an UV-B dose-effect is shown for the first time in mouse hepatocytes. Analysis of the model revealed a tight regulation emerging from high connectivity and spanning crosstalks and a particular importance of feedback loops. An unexpected feedback from Smac release to RIP could further increase complex II formation. The introduced Boolean model provides a comprehensive and coherent description of the apoptosis network behavior. It gives new insights into the complex interplay of pro- and antiapoptotic factors and can be easily expanded to other signaling pathways. [less ▲]

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See detailAnalyse der evolutiven Adaptation am Beispiel einer pyruvat-auxotrophen Escherichia coli-Mutante
Feuer, Ronny; Ederer, Michael; Gilles, Ernst Dieter et al

in Automatisierungstechnik (2008), 56

The biotechnological production of substances with help of microorganisms is an economically important application of systems biology. In this paper a pyruvate-auxotrophic Escherichia coli-strain is ... [more ▼]

The biotechnological production of substances with help of microorganisms is an economically important application of systems biology. In this paper a pyruvate-auxotrophic Escherichia coli-strain is utilized in order to activate alternative pyruvate synthesis pathways via evolutive adaptation. The outcome of the chemostat experiments are pyruvateprototrophic strains. Due to the activated alternative synthesis pathways, these strains are a basis for future industrial production-strains in order to systematically produce the intermediate products on these pathways. By means of a simple dynamical model of a chemostat, the evolutive adaptation in chemostat mode is studied. Rules to adjust the feeding concentration and the dilution rate of the bioreactor could be obtained in order to accelerate the evolutive adaptation towards a pyruvate-prototrophic strain. A flux balance analysis of the metabolic network of the pyruvate-auxotrophic strain results in 20 different alternative pathways. For a well arranged presentation of those pathways a reduced visualization method is introduced. [less ▲]

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See detailMethods for analysis of evolutive adaptation of E. coli
Feuer, Ronny; Ederer, Michael; Trachtmann, Natalie et al

in Proceedings of the SICE Annual Conference, September 17-20, 2007 Kagawa University, Takamatsu City, Japan (2007)

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