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

在过去的十年中，我们对空气污染对短期和长期人口健康影响的理解有了很大的进步，现在对空气污染对肺部以外的影响有了更好的理解。然而，我们对我们呼吸的空气中最有害的成分以及它们引起不良影响的机制的理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结果联系起来，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）。但是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、地壳物质和生物次生有机气溶胶控制着颗粒物质的质量。然而，氧化电位与人为的二次有机气溶胶和汽车非废气排放的金属。这表明，旨在减轻大气中存在的颗粒物质量的政策可能不会降低氧化电位或其他暴露措施。为了在环境中的化学品毒性中生存，所有物种的细胞都进化出一系列不同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，并提供了评估不同化学品或继发于氧化应激和炎症发展的反应的相对危害的手段。空气质量和毒理学，以调查暴露于大气颗粒物中不同化学功能对健康的影响。这该项目将由约克大学化学系沃尔夫森大气化学实验室的Jacqui汉密尔顿教授和Ally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。该项目将研究由生物和人为来源形成的SOA的不同毒性。该学生还将与项目合作伙伴罗兰沃尔夫教授和弗朗西斯科伊内斯塔-瓦奎拉博士在邓迪大学医学院进行暴露实验。在这里，生物/酶的方法将用于修改SOA提取物的组成，无论是系统地去除官能团或通过氧化转化。将确定组成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些类型的分子对人类健康构成最大风险。这将使政策制定者能够确定哪些气溶胶源应该减少，以尽量减少健康风险。学生将在HIPTOX项目中工作，该项目由自然环境研究理事会和医学研究理事会资助。该项目旨在开发一个独特的空气污染危害识别平台，并涉及来自曼彻斯特大学，伯明翰大学，爱丁堡大学，帝国理工学院伦敦大学，邓迪大学和NIHR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.