Glucose metabolism in Plasmodium falciparum trophozoites

The Snoep Lab’s core research efforts are in Computational Systems Biology; a combined experimental, modeling and theoretical approach to quantitatively understand the functional behavior of Biological Systems resulting from the characteristics of their components. Our main focus is on metabolism, of human pathogens such as Plasmodium falciparum, Mycobacterium tuberculosis, but also of breast cancer cell lines, and on modelling disease states such as glucose homeostatis in type 2 diabetes, and ...

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.

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

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

Experimental data set for the kinetic characterisation of GAPDH

Experimental data set for the kinetic characterisation of LDH

Experimental data set for the kinetic characterisation of PGI

Experimental data set for the kinetic characterisation of HK

Experimental data set for the kinetic characterisation of PFK

Experimental data set for the kinetic characterisation of PGK

Experimental data set for the kinetic characterisation of TPI

Experimental data set for the kinetic characterisation of the glucose transport reaction

Experimental data set for the kinetic characterisation of PK

Experimental data for the phosphoglycerate mutase (EC 5.4.2.12) activity.

Timecourses of GLC (starting at 5 mM) and LAC, PYR, GLY in the closed system.

Glycolytic model for Plasmodium falciparum; open system

Mathematica notebook for the parameterisation of the glucose transport rate equation based on SEEK linked experimental data.

Glycolytic model for Plasmodium falciparum; closed system

Mathematica notebook for the parameterisation of the G3PDH rate equation based on SEEK linked experimental data.

Mathematica notebook for the parameterisation of the ALD rate equation based on SEEK linked experimental data.

Mathematica notebook for the parameterisation of the ENO rate equation based on SEEK linked experimental data.

Mathematica notebook for the parameterisation of the GAPDH rate equation based on SEEK linked experimental data.

Mathematica notebook for the parameterisation of the PGI rate equation based on SEEK linked experimental data.

Mathematica notebook for the parameterisation of the LDH rate equation based on SEEK linked experimental data.

Mathematica notebook for the parameterisation of the TPI rate equation based on SEEK linked experimental data.

Mathematica notebook for the parameterisation of the PFK rate equation based on SEEK linked experimental data.

Mathematica notebook for the parameterisation of the PGK rate equation based on SEEK linked experimental data.

Mathematica notebook for the parameterisation of the PK rate equation based on the experimental SEEK data set

Mathematica notebook for the parameterisation of the PGM rate equation based on SEEK linked experimental data.

Mathematical model for HK kinetics, GLC and ATP saturation, and inhibition with G6P and ADP.

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 measurement of G3PDH activity in extracts.

SOP for measurement of ALD activity in extracts.

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 PGI activity in extracts.

SOP for measurement of PGM activity in extracts.

SOP for measurement of TPI activity in extracts.