A multi-disciplinary study into air pollution-associated transition metal homeostasis in the lungs.

对空气污染相关的肺部过渡金属稳态的多学科研究。

• 批准号: 2746858
• 金额: --
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2746858
• 关键词: multi; disciplinary; study; into; air

Particulate matter (PM) air pollution, which comes from a wide range of sources, is a leading risk factor for ill health. However, our understanding of effects on the lung of different components of PM, which relate to PM source, is poor. This is important in understanding why some types of PM may be more toxic than others. We are especially interested in how metals in PM may drive development and exacerbation of lung diseases such as idiopathic pulmonary fibrosis. Recent work in our group has shown that ultrafine PM (the smallest size fraction of PM) associated with shipping is enriched in vanadium and nickel, and that this PM, as well as vanadium and nickel alone, exerts multiple effects on exposed cells. We have also observed effects associated with other transition metals in particles from different sources, such as underground railways. We are now keen to understand how PM metals accumulate within cells, how cells maintain homeostasis of intracellular metals (the metallome), and the consequences if this fails.In this multidisciplinary project, we will study how transition metals, focusing initially on vanadium and nickel, may differentially accumulate within, and affect, the epithelial cells which line the alveoli, evaluating the roles played by metal transporting/binding proteins. The key aims are:1. investigate modulation of metal transporters and metal binding-proteins in response to vanadium and nickel exposure2. investigate accumulation of vanadium and nickel in exposed cells, and effects on the homeostasis of other metals, using state-of-the-art mass spectrometry techniques3. investigate the mechanisms through which the observed effects occur, and the consequences of their dysfunction, using pharmacological and/or genetic techniques.The results of this project will expand our understanding of how cells respond to different metal components of airborne PM, and how PM from different sources may be important in driving lung disease.

颗粒物 (PM) 空气污染来源广泛，是导致健康不良的主要风险因素。然而，我们对与 PM 来源相关的 PM 不同成分对肺部的影响了解甚少。这对于理解为什么某些类型的颗粒物可能比其他类型的毒性更大很重要。我们特别感兴趣的是PM中的金属如何促进特发性肺纤维化等肺部疾病的发展和恶化。我们小组最近的工作表明，与运输相关的超细颗粒物（颗粒物的最小尺寸部分）富含钒和镍，并且这种颗粒物以及单独的钒和镍对暴露的细胞产生多种影响。我们还观察到了来自不同来源（例如地铁）的颗粒中与其他过渡金属相关的影响。我们现在热衷于了解 PM 金属如何在细胞内积累，细胞如何维持细胞内金属（金属组）的稳态，以及如果失败的后果。在这个多学科项目中，我们将研究过渡金属（最初关注钒和镍）如何在肺泡内衬的上皮细胞内差异性积累并影响肺泡上皮细胞，评估金属转运/结合蛋白所发挥的作用。主要目标是： 1．研究金属转运蛋白和金属结合蛋白对钒和镍暴露的反应2。使用最先进的质谱技术研究暴露细胞中钒和镍的积累以及对其他金属稳态的影响3。利用药理学和/或遗传技术，研究观察到的效应发生的机制，以及其功能障碍的后果。该项目的结果将扩大我们对细胞如何对空气中 PM 的不同金属成分做出反应，以及不同来源的 PM 如何在导致肺部疾病方面发挥重要作用的理解。