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

活性氧物质（ROS）如过氧化氢（H2 O2）具有多种生物来源，并且作为氧代谢的副产物产生。ROS会导致与各种年龄相关疾病（包括癌症）有关的损害。因此，H2 O2也被用作信号分子，通过促进靶信号蛋白中特定半胱氨酸的氧化来上调ROS防御。我们对这些信号传导机制的理解主要基于酵母中涉及向细胞中加入H2 O2团的研究。因此，目前尚不清楚H2 O2如何到达并与其特定的靶信号蛋白反应，然后被大量的巯基过氧化物酶（2-Cys peroxiredoxins）去除。该项目旨在解决这个问题，利用模型酵母裂殖酵母中的化学遗传学方法来分析在特定细胞位置产生不同水平的H2 O2的影响。预计这种方法将提供一个更好的理解细胞内氧化还原信号的空间控制。

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.