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Jörg Schaber

About Jörg Schaber:

My group investigates dynamic regulation and control mechanisms of cellular signal transduction networks by a combination of theoretical, experimental and computational methods. We seek to make sense of our biological data with the help of mathematical models, which ideally enable us to make valid predictions for new experiments, thereby generating novel biological insights.

SEEK ID: https://fairdomhub.org/people/445

Locations: Germany, Sweden

Expertise: Image processing, Image analysis, Dynamic Systems, Signalling networks, dynamics of biological networks., parameter estimation, Databases, Data analysis, Systems Biology, Model selection, Identifiability, Cellular Senescence, Cell Cycle

Tools: Identifiability analysis, Fluorescence and confocal microscopy, parameter estimation, ODE, FACS, Model selection

ORCID: https://orcid.org/0000-0001-6971-2530

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SulfoSys - Biotec

Within the e:Bio - Innovationswettbewerb Systembiologie (Federal Ministry of Education and Research (BMBF)), the SulfoSYSBIOTECH consortium (10 partners), aim to unravel the complexity and regulation of the carbon metabolic network of the thermoacidophilic archaeon Sulfolobus solfataricus (optimal growth at 80°C and pH 3) in order to provide new catalysts ‘extremozymes’ for utilization in White Biotechnology.

Based on the available S. solfataricus genome scale metabolic model (Ulas et al., 2012)
...

Programme: e:Bio

Public web page: http://www.sulfosys.com/

ICYSB 2015 - International Practical Course in Systems Biology

Systems Biology studies the properties and phenotypes that emerge from the interaction of biomolecules where such properties are not obvious from those of the individual molecules. By connecting fields such as genomics, proteomics, bioinformatics, mathematics, cell biology, genetics, mathematics, engineering and computer sciences, Systems Biology enables discovery of yet unknown principles underlying the functioning of living cells. At the same time, testable and predictive models of complex
...

Programme: Independent Projects

Public web page: http://www.icysb.se/

University of Gothenburg

Country:  Sweden

City: Göteborg

Web page: http://www.gu.se/

Otto-von-Guericke University Magdeburg

Country:  Germany

City: Magdeburg

Web page: http://www.ovgu.de/

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Systems biology of the modified branched Entner-Doudoroff pathway in Sulfolobus solfataricus.
SulfoSys, SulfoSys - Biotec

Abstract (Expand)

Sulfolobus solfataricus is a thermoacidophilic Archaeon that thrives in terrestrial hot springs (solfatares) with optimal growth at 80 degrees C and pH 2-4. It catabolizes specific carbon sources, such … as D-glucose, to pyruvate via the modified Entner-Doudoroff (ED) pathway. This pathway has two parallel branches, the semi-phosphorylative and the non-phosphorylative. However, the strategy of S.solfataricus to endure in such an extreme environment in terms of robustness and adaptation is not yet completely understood. Here, we present the first dynamic mathematical model of the ED pathway parameterized with quantitative experimental data. These data consist of enzyme activities of the branched pathway at 70 degrees C and 80 degrees C and of metabolomics data at the same temperatures for the wild type and for a metabolic engineered knockout of the semi-phosphorylative branch. We use the validated model to address two questions: 1. Is this system more robust to perturbations at its optimal growth temperature? 2. Is the ED robust to deletion and perturbations? We employed a systems biology approach to answer these questions and to gain further knowledge on the emergent properties of this biological system. Specifically, we applied deterministic and stochastic approaches to study the sensitivity and robustness of the system, respectively. The mathematical model we present here, shows that: 1. Steady state metabolite concentrations of the ED pathway are consistently more robust to stochastic internal perturbations at 80 degrees C than at 70 degrees C; 2. These metabolite concentrations are highly robust when faced with the knockout of either branch. Connected with this observation, these two branches show different properties at the level of metabolite production and flux control. These new results reveal how enzyme kinetics and metabolomics synergizes with mathematical modelling to unveil new systemic properties of the ED pathway in S.solfataricus in terms of its adaptation and robustness.

Authors: Sofia Figueiredo, Theresa Kouril, D. Esser, Patrick Haferkamp, Patricia Wieloch, Dietmar Schomburg, Peter Ruoff, Bettina Siebers, Jörg Schaber

Date Published: 12th Jul 2017

Journal: PLoS One

Nested autoinhibitory feedbacks alter the resistance of homeostatic adaptive biochemical networks
ICYSB 2015 - International Practical Course in Systems Biology

Abstract (Expand)

Negative feedback control is a ubiquitous feature of biochemical systems, as is time delay between a signal and its response. Negative feedback in conjunction with time delay can lead to oscillations. … In a cellular context, it might be beneficial to mitigate oscillatory behaviour to avoid recurring stress situations. This can be achieved by increasing the distance between the parameters of the system and certain thresholds, beyond which oscillations occur. This distance has been termed resistance. Here, we prove that in a generic three-dimensional negative feedback system the resistance of the system is modified by nested autoinhibitory feedbacks. Our system features negative feedbacks through both input-inhibition as well as output-activation, a signalling component with mass conservation and perfect adaptation. We show that these features render the system applicable to biological data, exemplified by the high osmolarity glycerol system in yeast and the mammalian p53 system. Output-activation is better supported by data than input-inhibition and also shows distinguished properties with respect to the system's stimulus. Our general approach might be useful in designing synthetic systems in which oscillations can be tuned by synthetic autoinhibitory feedbacks.

Authors: J. Schaber, A. Lapytsko, D. Flockerzi

Date Published: No date defined

Journal: J R Soc Interface

Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeast
ICYSB 2015 - International Practical Course in Systems Biology

Abstract (Expand)

The high osmolarity glycerol (HOG) pathway in yeast serves as a prototype signalling system for eukaryotes. We used an unprecedented amount of data to parameterise 192 models capturing different … hypotheses about molecular mechanisms underlying osmo-adaptation and selected a best approximating model. This model implied novel mechanisms regulating osmo-adaptation in yeast. The model suggested that (i) the main mechanism for osmo-adaptation is a fast and transient non-transcriptional Hog1-mediated activation of glycerol production, (ii) the transcriptional response serves to maintain an increased steady-state glycerol production with low steady-state Hog1 activity, and (iii) fast negative feedbacks of activated Hog1 on upstream signalling branches serves to stabilise adaptation response. The best approximating model also indicated that homoeostatic adaptive systems with two parallel redundant signalling branches show a more robust and faster response than single-branch systems. We corroborated this notion to a large extent by dedicated measurements of volume recovery in single cells. Our study also demonstrates that systematically testing a model ensemble against data has the potential to achieve a better and unbiased understanding of molecular mechanisms.

Authors: J. Schaber, R. Baltanas, A. Bush, E. Klipp, A. Colman-Lerner

Date Published: 15th Nov 2012

Journal: Mol Syst Biol

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