Targeting new redox-signalling mechanisms as a therapeutic target to prevent age-associated diseases

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Reactive oxygen species (ROS) cause cell damage that is a major contributor to many age-associated diseases, including cancer, neurodegenerative and cardiovascular diseases. However, over the last 15 years, our view of how to limit this damage has been revolutionised. This follows the discovery that low levels of ROS have important, positive, signalling functions; initiating protective responses that maintain cell viability/organismal health. Despite, the increasing evidence that localised ROS increases can be beneficial, the mechanisms by which these ROS signals are transduced to protect against ageing/age-associated loss of tissue function/disease remain poorly understood. The student will be part of a multidisciplinary team combining a range of genetic, biochemical and computational approaches to provide answers to this fundamental question. The supervisors have identified several signalling proteins with important roles in health and disease as candidate ROS targets. The goal of this project will be to use a range of molecular biological and biochemical techniques (including genome editing, RNAi, immunoblotting confocal microscopy and proteomics) to investigate how ROS-induced oxidation of cysteines in these signalling proteins contribute to the positive effects of ROS in cell (yeast) and animal (the invertebrate Caenorhabditis elegans) models. By elucidating new signalling mechanisms that mediate effects of ROS and metabolism, this project will provide an essential initial step towards the goal of therapeutically enhancing ROS-induced protective responses, to counter the effects of ageing. The industrial placement will enable the student to use network pharmacology to identify the next step towards translating these discoveries.