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Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Speaker Abstracts
31
Modelling Blood Glucose Concentration in Malaria Patients
Jacky Snoep
, Kathleen Green, Danie Palm, Johann Eicher, David Van Niekerk.
Stellenbosch University, Stellenbosch, Western Cape, South Africa.
We use a hierarchical modelling approach to construct mathematical models for disease states at
the whole-body levels. The objective of the study is to use these models to simulate effects of
drug-induced inhibition of reaction steps on the whole-body physiology. We illustrate the
approach for glucose metabolism in malaria patients, by merging two detailed kinetic models for
glucose metabolism in the parasite
Plasmodium falciparum
and the human red blood cell with a
coarse-grained model for whole-body glucose metabolism.
The detailed kinetic model for glucose metabolism in
P. falciparum
was recently constructed in
our group (Penkler et al., 2015) on the basis of enzyme kinetic experimental data and has been
validated in isolated parasites and with infected red blood cells. The model gives accurate
predictions of glucose metabolism in infected red blood cells, and has been successfully tested in
its ability to pinpoint drug targets in the metabolic pathway. The model has been linked to a
genome scale metabolic model for the parasite to identify biomarkers.
In conclusions, the hierarchical modelling framework is capable of bridging the detailed enzyme
kinetic level (where drugs operate) with the physiological, whole body level, reflecting the
disease state.
Penkler, G., du Toit, F., Adams, W., Rautenbach, M., Palm, D.C., van Niekerk, D.D., and Snoep,
J.L. (2015) Construction and validation of a detailed kinetic model of glycolysis in Plasmodium
falciparum. FEBS. J. 282, 1481-1511.