Chemistry for monitoring mitochondrial protein homeostasis

线粒体是新陈代谢的核心。它们提供大部分驱动细胞机器的ATP。它们也是氧化还原信号传导的枢纽和程序性细胞死亡的关键。因此，线粒体失调导致严重的疾病。这些疾病包括神经变性、癌症和心力衰竭。Hartley小组开发的分子探针有助于显示线粒体活性氧（ROS）如何在细胞内产生，损伤和信号。在这个项目中，注意力转向线粒体蛋白质的生物合成和修饰，这似乎是许多线粒体疾病和衰老过程的基础。将开发分子探针来监测线粒体蛋白质的生物合成，并确定酶的活性和修饰线粒体基质内蛋白质的过程。该项目将涉及现代合成化学，分子探针和前药类型设计，以及交付的化学和生物学验证。它将以机械有机化学为基础，结合对物理化学性质和线粒体生物学的理解。总的来说，这项研究将提供有机化学和化学生物学的全面培训。

Mitochondria are central to metabolism. They provide most of the ATP that drives cellular machinery. They are also hubs for redox signalling and key to programmed cell death. Consequently, mitochondrial dysregulation contributes to serious conditions. These include neurodegeneration, cancer and heart failure. Molecular probes developed in the Hartley group have helped show how mitochondrial reactive oxygen species (ROS) are generated, damage and signal within cells. In this project attention turns to mitochondrial protein biosynthesis and modification, which appear to underpin many mitochondrial diseases and the process of ageing. molecular probes will be developed to monitor mitochondrial protein biosynthesis and to determine the activity of enzymes and processes that modify proteins within the mitochondrial matrix. The project will involve modern synthetic chemistry, molecular probe and prodrug-type design, and chemical and biological validation of delivery. It will be underpinned by mechanistic organic chemistry combined with an understanding of physicochemical properties and mitochondrial biology. Overall, the research will provide a thorough training in organic chemistry and chemical biology.