Regulation of cellular metabolism and intercellular communication by sodium signaling

我们的细胞不断地感知和运输环境中的离子。从胚胎发育到癫痫，从心脏病到癌症，我们的细胞对离子微环境变化的反应能力对健康衰老至关重要。我们最近发现了钠转运体和氨基酸代谢之间的新联系。这可能是一种将离子信号整合到细胞间通信中的机制。在这个项目中，你将以这些发现为基础，探索钠转运如何影响细胞代谢和细胞间的通讯，特别关注肿瘤/免疫细胞的相互作用。我们将使用一系列复杂的显微镜方法，如共聚焦显微镜和细胞学，来探索离子泵的功能活性及其对氨基酸代谢和免疫信号的影响。我们将使用药理学和遗传学（RNAi， CRISPR）技术来调节泵的表达。重要的是，我们将使用全细胞膜片钳记录和离子敏感染料的组合来测量泵的活性。我们还将使用分子细胞生物学方法研究离子泵活性对下游信号传导和细胞行为的影响。因此，该项目将使学生在该领域领先的实验室中接触到一系列尖端的细胞生物学技术。由于离子转运在正常细胞生理和许多疾病中起着关键作用，该项目有望为一个重要的、研究相对不足的信号传导机制提供新的机制见解。

Our cells constantly sense and transport ions present in their environment. Fromembryonic development to epilepsy to heart disease to cancer, our cells' abilityto respond to changes in the ionic microenvironment is essential for healthyageing. We recently discovered a new link between sodium transporters andamino acid metabolism. This could be a mechanism of integrating ionic signalsinto cell-cell communication. In this project, you will build on these findings andexplore how sodium transport affects cell metabolism and communicationbetween cells, with a specific focus on tumour/immune cell interaction.We will use a range of sophisticated microscopy approaches, e.g. confocalmicroscopy and ptychography, to explore the functional activity of ion pumps andtheir effect on amino acid metabolism and immune signalling. We will modulatepump expression using pharmacological and genetic (RNAi, CRISPR)techniques. Importantly, we will measure pump activity using a combination ofwhole cell patch clamp recording and ion-sensitive dyes. We will also study theeffects of ion pump activity on downstream signalling and cellular behaviourusing molecular cell biology approaches. The project will therefore expose thestudent to a range of cutting-edge cell biology techniques in labs that are leadingin this field. As ion transport plays a key role in normal cellular physiology and ina number of diseases, this project is expected to provide novel mechanisticinsights into an important, and relatively understudied signalling mechanism.