利用高通量RNA-seq深度测序探讨β-双酮类抗生素痕量复合污染对斑马鱼慢性致毒的分子机理

项目名称： 利用高通量RNA-seq深度测序探讨β-双酮类抗生素痕量复合污染对斑马鱼慢性致毒的分子机理

项目编号： No.31270548

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 王慧利

作者单位： 温州医科大学

项目金额： 77万元

中文摘要： β-双酮抗生素（DKAs）是一类假持久性新型污染物，其污水处理末端的痕量残留是水环境二次污染的主要源头，人们最易忽视其环境效应。申请人前期研究发现：痕量浓度DKAs复合污染可引起斑马鱼行为毒性和某些标志物的明显变化。本项目拟以污染源头的实际浓度和种类复合暴毒斑马鱼，利用高通量RNA-seq深度测序技术，完成斑马鱼不同发育期高度动态的转录组信息分析，建立转录本数据库并比较其差异，分析差异表达基因与疾病发生关系。并从转录后调控角度，挖掘显著动态变化的sRNA,进行sRNA靶基因功能分类和参与调控的代谢途径分析，建立sRNA鉴定和功能研究平台，探讨隐藏在基因信息层中全新的调控模式及其差异。整合已完成的2-DE数据，发现和验证一批调控枢纽中与药源性疾病相关的新型标志物。揭示其痕量浓度复合污染下慢性致毒的分子机理，建立系统毒理学模型体系，深入而系统地明确其生态风险，为药源性疾病的诊断与治疗提供依据。

中文关键词： 斑马鱼；双酮类抗生素；转录调控；非编码RNA；致毒机制

英文摘要： β-diketone antibiotics (DKAs) is one kind of false persistent pollutants, and its main source causing water environmental pollution is from the trace residue at the end of wastewater treatment plant. Therefore, its toxicological effect is easily neglected due to trace level in aquatic environment. In earlier experiment, we found that the compound exposure of DKAs to zebrafish resulted in the significant effect on its behavior and some markers. This proposal aims to reveal the molecular mechanism of chronic toxicity after the compound exposure of DKAs to zebrafish by the following researches: (1) The transcriptome information analysis at different developmental stages will be carried out by high throughput RNA-seq deep sequencing technique. Based on the previous results, the transcript database was then established, their differences were compared, and finally the relationship between the differentially expressed gene and disease occurrence was analyzed; (2) The significantly dynamic changing sRNA will be excavated from the view of post transcriptional regulation, and then its target gene functional classification and metabolic pathway analysis involved in the regulation are performed. The platform for sRNA identification and functional study will be established, which is used to probe the new regulation mode hid

英文关键词： Zebrafish；β-Diketone antibiotics；Transcriptional regulation；Non-coding RNA；Toxicological mechanism