Biophysical Society Thematic Meeting - November 16-20, 2015

Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Speaker Abstracts

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.

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