Advancing in vitro fish models for assessing environmental pharmaceutical risk: Integrating spatial-temporal kinetics of pharmaceutical uptake

这个跨学科的项目将采用多细胞和组学方法来表征生物转化，代谢和多组分体外鱼类模型中的效应的时空动力学。培养的鳃细胞将与肝脏类器官结合，以模拟整个生物体的吸收和代谢特性，从而促进更准确的环境药物风险评估。这项工作将在卡迪夫大学进行，但也有机会在埃克塞特大学、阿斯利康、阿尔德利公园的全球环境中心、麦克尔斯菲尔德和其他合作实验室工作。转录物和代谢物变化的时空成像将用于解决母体化合物影响的特定细胞，确定负责生物转化的细胞，并研究由此产生的异生物质代谢物的产生和作用。这个多组学项目将验证使用多组分体外模型预测环境药物风险。学生将成为最先进的空间转录组学和靶向代谢组学以及相关生物信息学的专家。实验室技能，包括体外细胞培养，一系列分子方法，包括qPCR和遗传操作，细胞成像，包括薄片和共聚焦显微镜。所有这些都是生态毒理学研究的前沿领域。

This interdisciplinary project will employ a multi-cellular and omic approach to characterised spatial-temporal kinetics of biotransformation, metabolism, and effect in a multi-component in vitro fish model. Cultured gill cells will be combined with liver organoids to mimic the absorption and metabolism properties of whole organisms facilitating more accurate environmental pharmaceutical risk assessment. The work will be based at Cardiff University, but there will be opportunities to spend time working at the University of Exeter, AstraZeneca, Global Environment site at Alderley Park, Macclesfield and other collaborating laboratories.The spatial-temporal imaging of transcript and metabolite changes will be used to resolve the specific cells impacted by parent compound, identify cells responsible for biotransformation & characterise the production & effect of xenobiotic metabolites this generated. This multi-omics project will validate the use of multi-component in vitro model for predicting environmental pharmaceutical risk.The student will become expert in state-of-the art spatial transcriptomic and targeted metabolomics together with the associated bioinformatics. Laboratory skills including in vitro cell culture, a range of molecular approaches including qPCR & genetic manipulation, cellular imaging including sheet and confocal microscopy. All are fields at the cutting edge of ecotoxicological research.