Dawie van Niekerk

Hypoglycaemia and lactic acidosis are key diagnostics for poor chances of survival in malaria patients. In this project we aim to test to what extent the metabolic activity of Plasmodium falciparum contributes to a changed glucose metabolism in malaria patients. The approach is to start with detailed bottom up models for the parasite and then merge these with more coarse grained models at the whole body level.

The Molecular Systems Biology project holds information for reproducing simulation figures in the journal. This can include experimental data files, model files and manuscript information.

The main objectives of SysMO-DB are to: facilitate the web-based exchange of data between research groups within- and inter- consortia, and to provide an integrated platform for the dissemination of the results of the SysMO projects to the scientific community. We aim to devise a progressive and scalable solution to the data management needs of the SysMO initiative, that:

• facilitates and maximises the potential for data exchange between SysMO research groups;
• maximises the ‘shelf life’ and ...

The investigation entails the construction and validation of a detailed mathematical model for glycolysis erythrocytes infected with the malaria parasite Plasmodium falciparum in the blood stage form.

The oxidative Weimberg pathway for the five-step pentose degradation to α ketoglutarate from Caulobacter crescentus is a key route for sustainable bioconversion of lignocellulosic biomass to added-value products and biofuels. Here, we developed a novel iterative approach involving initial rate kinetics, progress curves, and enzyme cascades, with high resolution NMR analysis of intermediate dynamics, and multiple cycles of kinetic modelling analyses to construct and validate a quantitative model ...

The gluconeogenic conversion of 3-phosphoglycerate via 1,3-bisphosphoglycerate to glyceraldehyde-3-phosphate was compared at 30 C and at 70 C. At 30 C it was possible to produce 1,3-bisphosphoglycerate from 3-phosphoglycerate with phosphoglycerate kinase, but at 70 C, 1,3- bisphosphoglycerate was dephosphorylated rapidly to 3-phosphoglycerate, effectively turning the phosphoglycerate kinase into a futile cycle. At both temperatures it was possible to convert 3-phosphoglycerate to glyceraldehyde ...

Drug detoxification dynamics explain the postantibiotic effect

Protein abundance of AKT and ERK pathway components governs cell-type- specific regulation of proliferation

The investigation entails the construction and validation of a detailed mathematical model for glycolysis of the malaria parasite Plasmodium falciparum in the blood stage trophozoite form.

Design principles of nuclear receptor signaling: how complex networking improves signal transduction

Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range

This study includes the experimental data for model validation and the model predictions of that data set.

This study includes the experimental data for model validation and the model predictions of that data set.

After the removal of the extracellular antibiotic, efflux and inhibition dynamics combine to delay the synthesis of ribosomes in a concentration-dependent manner (panel ii). Colors indicate increasing antibiotic concentration, as shown in panel ii.

SED-ML simulation https://jjj.bio.vu.nl/models/experiments/srimani2017_fig2cii/simulate

Growth-factor deprived mCFU-E cells (5x106 cells per condition) and BaF3-EpoR cells (1x107 cells per condition) were stimulated with different Epo doses and absolute concentrations were determined for pEpoR (B), pAKT (C), ppERK (D). The scale for pS6 (E) was estimated in arbitrary units. GTP-Ras (F) and ppERK were determined upon stimulation with indicated, color-coded Epo doses. pEpoR was analyzed by immunoprecipitation followed by immunoblotting, GTP-Ras was analyzed after pulldown using a ...

Transcriptional response to a sudden increase in extracellular ligand (hormone), for the six network designs of (A). The transcriptional response is taken to equal the ratio ReNrL/Retotal, i.e., the fraction of REs attaching ligand-bound NR. The ligand concentration was increased from 0 to 0.005 nM and maintained constant at the latter level. The observation that design 6 is higher than all other designs at long times is robust for parameter changes up to a factor of 3.

For all experiments, primary CFU-E cells were starved and stimulated with 5 U/ml Epo. At the indicated time points, samples were subjected to quantitative immunoblotting. Experimental data (black circles) with estimated standard errors and trajectories of the best fit (solid lines) are represented. Mass spectrometry data represent replicates of four independent experiments.

This study includes the experimental data for model validation and the model predictions of that data set.

This study includes all the experimental data, SOPs and modelling files for the individual reactions used for the model construction.

Kinetic characterisation en mathematical modelling of HK.

Kinetic characterisation en mathematical modelling of PGI.

Kinetic characterisation en mathematical modelling of PFK.

Kinetic characterisation en mathematical modelling of ALD.

Kinetic characterisation en mathematical modelling of TPI.

Kinetic characterisation en mathematical modelling of G3PDH.

Kinetic characterisation en mathematical modelling of GAPDH.

Kinetic characterisation en mathematical modelling of PGK.

Kinetic characterisation en mathematical modelling of PGM.

Kinetic characterisation en mathematical modelling of ENO.

Kinetic characterisation en mathematical modelling of PK.

Kinetic characterisation and mathematical modelling of LDH.

SED-ML simulation: https://jjj.bio.vu.nl/models/experiments/penkler2aa_experiment-user/simulate

Volumes in fL, time in hours.

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See 'Figure 3 legend' and 'Materials and methods - Time course experiments, cell lysis and quantitative immunoblotting' for details.

Experimental data set for the kinetic characterisation of G3PDH

Experimental data set for the kinetic characterisation of ALD

Experimental data set for the kinetic characterisation of ENO

SOP for the determination of external metabolites (Glc, Pyr, Gly, Lac) in intact trophozoite incubations, and for the determination of intracellular metabolite concentrations.

SOP for the cultivation conditions of Plasmodium falciparum, including the protocol for synchronisation.

SOP for measurement of G3PDH activity in extracts.

SOP for measurement of ALD activity in extracts.

SOP for measurement of glucose transport activity in intact trophozoites.

SOP for measurement of GAPDH activity in extracts.

SOP for measurement of ENO activity in extracts.

SOP for measurement of HK activity in extracts.

SOP for measurement of PFK activity in extracts.

SOP for measurement of LDH activity in extracts.

SOP for measurement of PGK activity in extracts.

SOP for measurement of PK activity in extracts.

SOP for measurement of PGM activity in extracts.

SOP for measurement of PGI activity in extracts.

SOP for measurement of PGM activity in extracts.

SOP for measurement of TPI activity in extracts.

SOP for the isolation of intact Plasmodium falciparum trophozoites from infected red blood cells and the preparation of a cell free extract that can be used for kinetic analyses.