Characterisation of air pollution induced cellular dysfunction using organoid models of trophoblast stem cells

空气污染是不良出生结果的公认风险因素，可能对儿童健康产生长期有害影响，但我们对所涉及的机制以及不同的空气接触在多大程度上导致空气污染的毒理学影响的理解存在重大知识差距。先前我们已经证明，用柴油发动机颗粒和室内灰尘处理胎盘外植体会改变hCG分泌，这表明这种暴露可能导致胎盘功能障碍，从而导致不良妊娠结局。该项目的总体目标是更好地描述这种暴露如何导致这种功能障碍，具体目标是-调查空气传播物质对胎盘的直接和间接影响-确定空气污染对滋养细胞内分泌功能的细胞和分子影响机制。博士候选人将使用滋养层干细胞的类器官模型来检查不同污染物（尤其是颗粒物）对细胞的影响和细胞信号的变化——通过在家中使用污染监测器来复制现代家庭暴露的模式，以更好地了解和表征孕妇家中的颗粒物。该项目将利用现有的一个多地点项目，该项目最初旨在查明产前和围产期接触有害空气污染的情况，以便最终减轻对儿童健康的负面影响。成功的候选人将被嵌入由污染科学家、数量生物学家、数据科学家和临床学者组成的研究团队，以获得数量生物学和物理科学的跨学科培训。

Air pollution is a recognised risk factor for adverse birth outcomes and may have longer-term detrimental effects on children's health but there are significant knowledge gaps in our understanding of the mechanisms involved and the extent to which different airborne exposures contribute to the toxicological impact of air pollution. Previously we have shown that treatment of placental explants with diesel engine particulate and house dust altered hCG secretion, suggesting that such exposures might contribute to placental dysfunction that underlies adverse pregnancy outcomes. The overall aim of this project is to better characterise how such exposures contribute to this dysfunction and the specific aims are to - investigate the direct and indirect effects of airborne materials on the placenta - determine the mechanism of cellular and molecular effects of air pollution on trophoblast endocrine function. Doctoral candidates will use organoid models of trophoblast stem cells to examine cellular effects and cell signalling changes that occur with different pollutants (especially particulate matter)- replicate the pattern of modern household exposure by using pollution monitors in the home to better understand and characterise particulate matter within homes of pregnant women.This project will take advantage of an existing multisite project that aims initially to identify harmful air pollution exposures in the pre- and peri-natal period so as to ultimately mitigate negative health effects on children. The successful candidate will be embedded within the study team, that includes pollution scientists, quantitative biologists, data scientists and clinical academic, so as to obtain interdisciplinary training in quantitative biology and the physical sciences.