Understanding the immunomodulatory activity of pharmaceuticals in zebrafish using high content imaging and phenotypic profiling

该项目的目的是整合尖端的高含量（HC）成像技术和大数据分析，以推进我们对药物如何调节鱼类免疫反应的理解。提出了三个目标：1)采用一种创新的hc细胞成像技术，称为细胞绘画，来表征暴露于药物的分离斑马鱼细胞（中性粒细胞，成纤维细胞样ZF4）的表型特征。2)利用共聚焦显微镜定量药物对无保护转基因斑马鱼幼虫体内中性粒细胞动力学的影响。3)开发一个计算管道，整合体外和体内表型和功能数据（1300多个参数），以表征药物的鱼特异性免疫调节活性谱。

The aim of this project is to integrate cutting-edge high-content (HC)-imaging technologies and big data analysis to advance our understanding of how pharmaceuticals modulate immune responses in fish. Three objectives are proposed:1) Adopt an innovative HC-cell-imaging technique, called Cell Painting, to characterise the phenotypic signature of isolated zebrafish cells (neutrophils, fibroblast-like ZF4) exposed to pharmaceuticals.2) Utilise confocal microscopy to quantify the effect of pharmaceuticals on neutrophil dynamics in-vivo using non-protected transgenic zebrafish larvae.3) Develop a computational pipeline that integrates in-vitro and in-vivo phenotypic and functional data (1300+ parameters) to characterise the fish-specific immunomodulatory activity profile of pharmaceuticals.