Modelling the redox pathway in Trypanosoma brucei

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About Modelling the redox pathway in Trypanosoma brucei


|free text=}} Trypanosoma brucei is the causative agent of African Sleeping Sickness in humans. To maintain its redox balance, this parasite uses an unusual thiol, called trypanothione. This thiol is synthesised from glutamate and cysteine, by a small enzymatic pathway consisting of the enzymes GSH1, GSH2, TryS and trypanothione reductase. We know the relevant rate equations for two of the three enzymes and for the remaining enzyme enough data is available to derive a rate equation. For all these enzymes the values of kinetic parameters have been measured in the same in vivo-like buffer. Enzyme concentrations and intermediate concentrations have been determined or literature data is available. With this information we can make a bottom-up kinetic model of this small pathway and propose model validation experiments (which will be done by a collaborating group in Heidelberg). This will help us to get quantitative understanding of the trypanothione synthesis pathway.

In this project, you will construct the kinetic model of the trypanothione synthesis pathway. Ultimately this model should be connected to our existing and well-validated model of T. brucei glucose metabolism.