Targeting Redox-regulated Chaperone/Scaffold proteins as a therapeutic approach to prevent age-associated diseases

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Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) have various biological sources and are generated as byproducts of oxygen metabolism. ROS cause damage that is linked to with various age-associated diseases including cancer. Hence, H2O2 is also employed as a signalling molecule to upregulate ROS defences by promoting the oxidation of specific cysteines in target signaling proteins. Our understanding of these signaling mechanisms is largely based on studies in yeast involving the addition of an H2O2 bolus to cells. Hence, it remains unclear how H2O2 reaches and reacts with its specific target signaling protein/s before it is removed by abundant thiol peroxidases, the 2-Cys peroxiredoxins. This project aims to address this question by utilising a chemogenetic approach in the model yeast Schizosaccharomyces pombe to analyse the effects of producing different levels of H2O2 in specific cell locations. It is expected this approach will provide a better understanding of the spatial control of intracellular redox signalling.