Probing the role of chemical composition on the toxicity of atmospheric particles

在过去十年中，我们对空气污染对人口短期和长期健康影响的认识有了很大的进步，现在对空气污染对肺部以外的影响有了更好的了解。然而，我们对我们呼吸的空气中最有害的成分及其引起不良影响的机制的了解仍然存在重大差距。为了将空气污染的化学成分与不利的健康后果联系起来，需要进行多学科研究，以了解潜在的因果机制。大气气溶胶极其复杂，含有数千种化合物（Stewart等人，2021 https://doi.org/10.5194/acp-21-2407-2021, 2021）。但哪些会对人体产生毒性作用呢？欧洲最近的一项研究表明，无机物质、地壳物质和生物次生有机气溶胶控制着颗粒物的质量。然而，氧化电位与车辆非废气排放的人为二次有机气溶胶和金属有关。这表明，旨在减少大气中颗粒质量的政策可能不会降低氧化电位或其他暴露措施。为了在环境中化学物质的毒性下生存，所有物种的细胞都进化出了一系列独特的应激诱导细胞保护机制。因此，这些途径在体内的激活提供了毒性的早期生物标志物，以及评估不同化学物质或氧化应激和炎症发展继发反应的相对危害的手段。这个独特的跨学科项目将把气溶胶化学、空气质量和毒理学方面的研究人员联系起来，研究暴露于大气颗粒物中不同化学功能对健康的影响。该项目将由约克大学化学系沃尔夫森大气化学实验室的杰基·汉密尔顿教授和艾丽·刘易斯教授共同监督。为了简化大气的复杂性，使用模拟室的实验室实验可用于从单个挥发性有机化合物中产生二次有机气溶胶（SOA）。学生将使用最先进的色谱和高分辨率质谱工具来了解SOA的组成。该项目将调查生物源和人为源形成的SOA的不同毒性。该学生还将在邓迪大学医学院与项目伙伴Roland Wolf教授和Francisco insta - vaquera博士一起进行暴露实验。这里将使用生物/酶的方法来修改SOA提取物的组成，要么系统地去除官能团，要么通过氧化转化。将测定其成分的变化和相应的毒性变化。这将有助于评估气溶胶颗粒中哪种类型的分子对人类健康构成最大风险。这将使决策者能够确定应该减少哪些气溶胶源，以最大限度地降低健康风险。该学生将在由自然环境研究委员会和医学研究委员会资助的HIPTOX项目中工作。该项目旨在开发一个独特的空气污染危害识别平台，涉及来自曼彻斯特大学、伯明翰大学、爱丁堡大学、伦敦帝国理工学院、邓迪大学和英国国立卫生研究院曼彻斯特临床研究机构的合作者。

Over the last decade our understanding of the impact of air pollution on both short- and long-term population health has advanced considerably and there is now a better understanding of the impacts of air pollution beyond the lungs. However, there are still major gaps in our understanding of the most harmful components within the air we breathe and the mechanisms by which they induce adverse effects. In order to link the chemical composition of air pollution with adverse health outcomes, multidisciplinary research is needed to understand the underlying causal mechanisms.Atmospheric aerosols are extremely complex, containing many thousands of compounds (Stewart et al., 2021 https://doi.org/10.5194/acp-21-2407-2021, 2021). But which ones cause toxic effects in the human body?A recent study in Europe showed that inorganic species, crustal materials and biogenic secondary organic aerosols control the mass of particulate matter. However, oxidative potential was associated with anthropogenic secondary organic aerosols and metals from vehicle non-exhaust emissions. This suggests that policies that aim to mitigate only the mass of particles present in the atmosphere may not reduce oxidative potential or other measures of exposure.To survive the toxicity of chemicals in the environment, cells across all species have evolved a range of distinct stress-inducible cytoprotective mechanisms. The activation of these pathways in vivo therefore provides an early biomarker of toxicity and a means of evaluating the relative hazard of different chemicals or responses secondary to the development of oxidative stress and inflammation.This unique cross disciplinary project will link researchers in aerosol chemistry, air quality and toxicology to investigate the health effects of exposure to different chemical functionalities within atmospheric particulate matter.This project will be co-supervised by Prof Jacqui Hamilton and Prof Ally Lewis at the Wolfson Atmospheric Chemistry Laboratories in the Chemistry Department at the University of York. In order to simplify the complexity of the atmosphere, laboratory experiments using simulation chambers can be used to create secondary organic aerosols (SOA) from individual volatile organic compounds. The student will use state of the art chromatographic and high resolutions mass spectrometric tools to understand the composition of SOA. This project will investigate the differential toxicity of SOA formed from biogenic and anthropogenic sources.The student will also carry out exposure experiments at the School of Medicine at the University of Dundee with project partners Prof Roland Wolf and Dr Francisco Inesta-Vaquera. Here biological/enzymatic approaches will be used to modify the composition of SOA extracts, either systematically removing functional groups or via oxidative transformation. The change in composition and corresponding change in toxicity will be determined. This will allow an assessment of which types of molecules in aerosol particles pose the greatest risk to human health. This will allow policy makers to identify which aerosol sources should be reduced to minimise health risks.The student will work within the HIPTOX project, funded by the Natural Environment Research Council and the Medical Research Council. This project aims to develop a unique Air Pollution Hazard Identification Platform and involves collaborators from Universities of Manchester, Birmingham, Edinburgh, Imperial College London, Dundee and the NIHR Manchester Clinical Research Facility.