Structural and functional interactions of mitochondrial haemoglobin and ATP synthase in ageing

我们最近描述了线粒体细胞器中存在血红蛋白(Shephard等人，2014年和2016年)。这一发现对我们理解细胞中的能量产生具有重大意义。南极的“白色”冰鱼(来自脊椎动物亚目)有缺乏蛋白质血红蛋白的白色血液。通过我们的合作者，我们将能够分析这些和密切相关的红鱼的组织，这些红鱼确实含有血红蛋白。学生将研究线粒体血红蛋白相互作用组蛋白，它们的表达/分布，并比较红鱼和白鱼中线粒体酶复合体的功能。学生还将研究这些蛋白质的亚线粒体定位。同时，学生将研究线虫蛋白质中球状颗粒的击倒效应。我们将使用我们的mitoGFP菌株和高分辨率呼吸计量仪检查珠蛋白击倒的线粒体形态和功能的变化。学生将作为查克拉巴蒂小组的一部分进行分子/生化工作。第二部分由戴夫·斯科特在《生物科学/RCAH》杂志上指导，将使用荧光超分辨率显微镜技术研究线粒体血红蛋白的潜在相互作用。50%的人将在钻石光源工作，由张培军监督。最先进的冷冻电子显微镜技术将用于阐明突变物种的线粒体表型。

We recently described the presence of haemoglobin in the mitochondrial organelle (Shephard et al.,2014 and 2016). This finding has major implications in our understanding of energy production in the cell. The Antarctic 'white' ice fish (from the sub-order Notothenioid) have white blood which lacks the protein haemoglobin. Through our collaborators we will be able to analyse tissues from these and closely related red fish that do have haemoglobin. The student will examine the mitochondrial haemoglobin interactome proteins, their expression/distribution and compare mitochondrial enzyme complex function in both the red and white fish. The student will also examine the sub-mitochondrial localisation of these proteins. In parallel, the student will examine the effect of knock-down of the glob in proteins in C.elegans. Globin knockdowns will be examined for changes in mitochondrial form and function using our mitoGFP strain and high resolution respirometry.The student will carry out molecular/biochemical work as part of the Chakrabarti group. The second part is supervised by Dave Scott in Biosciences/RCaH and will examine the potential interactions of mitochondrial haemoglobin using fluorescent super resolution microscopy techniques. Fifty percent will be based at the Diamond Light Source and supervised by Peijun Zhang. State of the art cryo-electron microscopy techniques will be used to elucidate the mitochondrial phenotype of the mutant species.