Investigations

Aim: To provide quantitative data that will allow modeling of gene expression for all enzymes of redox metabolism and the pentose phosphate pathway. Modeling will be used to predict enzyme levels based on the integration of an RNA degradation model with translation and protein degradation rates.

Plan: The amounts of a protein in a cell can be determined by the rates of transcription, mRNA processing, translation, mRNA turnover and protein degradation. In trypanosomes analysis is simpler because ...

Aim. To provide critical quantitative parameter information and to model redox balance by determining the cellular concentration of all enzymes involved in the trypanothione-dependent hydroperoxide detoxification system of trypanosomes and by performing the kinetic characterization of the involved enzymes under pseudo-physiological conditions.

The aims of this investigation is to quantify metabolites associated with pathways involved in stress responses for parameterising models of oxidative stress metabolism; the measurement of metabolic fluxes of metabolites of interest with intracellular concentrations

Multiply perturbations of trypanosome redox metabolism, closing the feedback loop between experimentation and in silioc modelling, allowing model refinement or, where there are unexpected outcomes, re-evaluation. Providing a dynamic picture of cell physiology by examining programmed metabolic changes during the developmental life-cycle of these parasites as they adapt to very different external milieus, including distinct levels of oxidative stress and unique adaptations of their redox balance ...

Aim. Constructing a predictive, dynamic model of the redox metabolism of trypanosomes. Aided by this model we will quantify the impact of gene-expression and metabolic regulation on redox metabolism. The model will be constructed in an iterative cycle of experimentation – modelling – analysis – experimentation, such that it can be extended and refined based on new experimental insights.