Brett Olivier

Projects: Not specified

Institutions: Not specified

https://orcid.org/0000-0002-5293-5321
Mary-Ann Blätke programme_administrator

Projects: Not specified

Institutions: Not specified

https://orcid.org/0000-0002-4790-7377
Egils Stalidzans project_administratorprogramme_administrator

Projects: LEANPROT, FAIRDOM user meeting, Rhodolive

Institutions: Latvia University of Agriculture, Institute of Microbiology and Biotechnology, University of Latvia

https://orcid.org/0000-0001-6063-0184
Matthias König project_administratorasset_housekeeperasset_gatekeeper

Projects: Kinetics on the move - Workshop 2016, Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), FAIRDOM user meeting, COMBINE Multicellular Modelling, FAIRDOM & LiSyM & de.NBI Data Structuring Training

Institutions: Charité University Medicine Berlin, Humboldt-Universität zu Berlin, Humboldt University Berlin

https://orcid.org/0000-0003-1725-179X
Ali Salehzadeh-Yazdi palproject_administrator

Projects: SYSTERACT, Kinetics on the move - Workshop 2016, BESTER, iRhythmics, GB-XMap: Assessing the risk of gut-brain cross-diseases Investigating the gut-brain-axis, SASKit: Senescence-Associated Systems diagnostics Kit for cancer and stroke

Institutions: University of Rostock

https://orcid.org/0000-0002-1678-0051
Eduard Kerkhoven project_administrator

Projects: SilicoTryp, SYSTERACT, SynBio4Flav

Institutions: University of Glasgow, Chalmers University of Technology

https://orcid.org/0000-0002-3593-5792
Natalie Stanford project_administrator

Projects: SysMO DB, Whole body modelling of glucose metabolism in malaria patients, Manchester Institute for Biotechnology, FAIRDOM, ICYSB 2015 - International Practical Course in Systems Biology, GenoSysFat, DigiSal, FAIRDOM user meeting

Institutions: University of Manchester - Department of Computer Science, Manchester Centre for Integrative Systems Biology, University of Manchester

https://orcid.org/0000-0003-4958-0184
Detailed kinetic model of yeast glycolytic oscillation - I
SysMO DB

An existing detailed kinetic model for the steady-state behavior of yeast glycolysis was tested for its ability to simulate dynamic behavior. This model (dupreez1) is the basis kinetic model derived from that published by Teusink et al., 2000 (PMID: 10951190).

Creators: Franco du Preez, David D van Niekerk

Submitter: Franco du Preez

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Towards the digital twin: personalised modelling of clinical heterogeneity between medium-chain acyl-CoA dehydrogenase patients
PoLiMeR - Polymers in the Liver: Metabolism and Regulation

Abstract (Expand)

Background: Monogenetic inborn errors of metabolism (IEM) cause a wide phenotypic heterogeneity that may even differ between family members carrying the same genetic variant. Computational modelling … of metabolic networks may identify putative sources of this inter-patient heterogeneity. Here, we focus on inherited mitochondrial fatty-acid oxidation (mFAO) deficiencies, particularly on medium-chain acyl-CoA dehydrogenase deficiency (MCADD), the most common inborn error of mFAO disorder. It is an enigma why some MCADD patients – if untreated – are at risk to develop severe metabolic decompensations, whereas others remain asymptomatic throughout life. We hypothesised that an ability to maintain an increased free mitochondrial CoA (CoASH) and pathway flux might distinguish asymptomatic from symptomatic patients. Results: We built and experimentally validated a computational model of the human liver mFAO based on detailed kinetic analysis of human enzymes. Metabolite pools were partitioned between the enzymes in the mitochondrial matrix and the membrane-bound enzymes according to their hydrophobicity. Metabolite partitioning improved model predictions. MCADD substantially reduced pathway flux and CoASH concentration, the latter due to the sequestration of CoA in medium-chain acyl-CoA esters. Analysis of urine from MCADD patients obtained during a metabolic decompensation showed excessive accumulation of medium- and short-chain acyl-carnitines, in agreement with the acyl-CoA pool in the MCADD model. According to the model, upregulation of the enzymes SCAD, MTP and ACOT or downregulation of CPT2 would rescue both flux and CoASH. Proteome analysis of MCADD patient-derived fibroblasts revealed that elevated levels of MTP and SCAD indeed correlated with a clinically asymptomatic state. Personalised models based on these proteomics data confirmed an increased pathway flux and free CoASH concentration in the model of an asymptomatic patient compared to those of symptomatic MCADD patients. Conclusion: We present a detailed, validated kinetic model of mFAO in human liver, with solubility-dependent metabolite partitioning. Personalised modelling of individual patients provides an explanation for phenotypic heterogeneity among MCADD patients. Further development of personalised metabolic models is a promising direction to improve individualised risk assessment, management, and monitoring for IEMs.

Authors: Christoff Odendaal, Emmalie Jager, Anne-Claire M. F. Martines, Marcel A. Vieira-Lara, Nicolette C. A. Huijkman, Ligia Akemi Kiyuna, Albert Gerding, Justina C. Wolters, Rebecca Heiner-Fokkema, Karen van Eunen, Terry G.J. Derks, Barbara Bakker

Date Published: No date defined

Publication Type: Journal

SABIO-RK, von Daten in der Publikation zur Suchlösung für Spezialisten
FAIRDOM, LiSyM Core Infrastructure and Management (LiSyM-PD), Kinetics on the move - Workshop 2016

Abstract

Not specified

Authors: Wolfgang Müller, Meik Bittkowski, Martin Golebiewski, Renate Kania, Maja Rey, Andreas Weidemann, Ulrike Wittig

Date Published: 1st Mar 2017

Publication Type: Journal

From steady-state to synchronized yeast glycolytic oscillations I: model construction
SysMO DB

Abstract (Expand)

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 J doi:10.1111/j.1742-4658.2012.08658.x], 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: , David D van Niekerk, Bob Kooi, Johann M Rohwer,

Date Published: 21st Jun 2012

Publication Type: Not specified

From steady-state to synchronized yeast glycolytic oscillations II: model validation
SysMO DB

Abstract (Expand)

In an accompanying paper [du Preez et al., (2012) FEBS J doi: 10.1111/j.1742-4658.2012.08665.x], 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: , David D van Niekerk,

Date Published: 13th Jun 2012

Publication Type: Not specified

Sustained glycolytic oscillations in individual isolated yeast cells
SysMO DB

Abstract (Expand)

Yeast glycolytic oscillations have been studied since the 1950s in cell-free extracts and intact cells. For intact cells, sustained oscillations have so far only been observed at the population level, … i.e. for synchronized cultures at high biomass concentrations. Using optical tweezers to position yeast cells in a microfluidic chamber, we were able to observe sustained oscillations in individual isolated cells. Using a detailed kinetic model for the cellular reactions, we simulated the heterogeneity in the response of the individual cells, assuming small differences in a single internal parameter. This is the first time that sustained limit-cycle oscillations have been demonstrated in isolated yeast cells. Database The mathematical model described here has been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.biochem.sun.ac.za/database/gustavsson/index.html free of charge.

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

Date Published: 23rd May 2012

Publication Type: Not specified

Graph based storage and retrieval of computational models
SysMO DB

Presented by Ron Henkel at SySMO PALs meeting 29-30 November 2012 in Heidelberg

Creator: Ron Henkel

Submitter: Olga Krebs

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