Chemical biology tools for investigating the chemistry of cellular REDOX stress

细胞内环境的变化可以被认为是细胞化学的变化。细胞环境可以被认为跨越了还原条件（通常以缺氧和含有氢的化学物质的存在为特征）和氧化条件（通常以氧气和含活性氧的存在为特征）之间的光谱。还原到氧化环境的光谱被称为氧化还原化学。细胞内的氧化还原环境是由外部刺激引起的，并影响细胞的功能。因此，氧化还原环境可引起导致疾病的细胞变化。在这项工作中，我们提出反过来也是正确的-细胞在给定时间的氧化还原状态将提供对特定细胞命运的预测信息。因此，如果有可能获得细胞氧化还原状态的全局图像，这将是预测细胞命运的革命性方法，从而治疗疾病。为了使这项新技术发挥作用，我们需要一系列分子工具来告诉我们在任何给定时间氧化还原状态的给定组分。我们的工作目的是开发和验证检测影响细胞氧化还原状态的细胞内分子的工具，并提供该状态的成像反馈。通过梳理这些分子工具的反馈，我们可以推断出总体氧化还原状态的信息。为了实现这一目标，我们组建了一个具有广泛技能的团队来制作所提出的分子工具。我们的团队包括合成无机和有机化学家，熟练掌握一系列成像技术的人员，以及能够应用我们将制造的分子工具的生物科学家。只有将我们团队中每个人的技能结合起来，我们才能实现这个雄心勃勃、但可能具有革命性的研究项目的目标。

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.