Nutrient Uptake and Metabolism - Project A3

TBA

As a parasite that spends most of its life-cycle inside host cells, the lipid metabolism of Plasmodium falciparum is of particular importance. Lipids are important as building blocks of parasite derived membranes, for the modification of host membranes, for signalling events and as energy storage. Mathematical modelling of lipid metabolism with the classical approaches such as stoichiometric networks and ordinary differential equation systems has not yet provided satisfactory insights, due to the complexity of lipid metabolism characterised by many different species with only slight differences and by promiscuous multifunctional enzymes. In this project, we will apply different modelling approaches such as ordinary differential equations or object-oriented stochastic model approach to explain lipid dynamics. Its suitability has been demonstrated before for yeast lipid behaviour during progression through the cell cycle. This approach allows tracking the dynamics of all lipid species with different fatty acids, different degrees of saturation and different head groups over time as well as the location-dependent distribution. Hence changes can be monitored by looking at lipid variation across different developmental stages, different organelles, different host cells or different sexes. By analysing the effect of parameter changes, potential mutations in the catalysing enzymes or provision of different precursors the model will be able to deliver predictions about potential drug targets or mutation effects that can then be tested experimentally.

Keywords: Development of a mathematical model for lipid metabolism, comparison male vs female lipid composition, effect of chemical perturbations on lipid metabolism