Chemical biology tools for investigating the chemistry of cellular REDOX stress

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Changes in the environment inside cells can be considered as alterations in cellular chemistry. The cellular environment can be thought to span a spectrum between reducing conditions (often characterised by a lack of oxygen, and the presence of chemicals that contain hydrogen) and oxidising conditions (often characterised by the presence of oxygen and reactive oxygen-containing species). The spectrum of REDucing to OXidising environment is known as REDOX chemistry. The REDOX environment in the cell results from external stimuli, and affects the function of the cell. Consequently, the REDOX environment can give rise to cellular changes that result in diseases. In this work, we propose that the reverse is also true - that the REDOX state of a cell at a given time will provide predictive information on the fate of a particular cell. Therefore, if it were possible to gain a global picture of the cellular REDOX state, this would be a revolutionary way of predicting cell fate, and hence treating disease. For this new technique to work we need a range of molecular tools that tell us about a given component of the REDOX state at any given time. The aim of our work is to develop and validate tools that detect the intracellular molecules that affect the cellular REDOX state, and provide imaging feedback on that state. By combing the feedback from several of these molecular tools we can infer information on the overall REDOX state. To achieve this aim we have assembled a team of people with the wide range of skills required to make the proposed molecular tools. Our team includes synthetic inorganic and organic chemists, people skilled in a range of imaging techniques, and biological scientists who will be able to apply the molecular tools that we will make. Only by combining the skills of everybody in our team will we be able to achieve the aims of this ambitious, but potentially revolutionary, programme of research.