柔嫩艾美尔球虫组蛋白去乙酰化酶3的生化特性及其药靶有效性研究

项目名称： 柔嫩艾美尔球虫组蛋白去乙酰化酶3的生化特性及其药靶有效性研究

项目编号： No.31302084

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 农业科学

项目作者： 殷昊

作者单位： 中国农业科学院兰州兽医研究所

项目金额： 24万元

中文摘要： 艾美耳球虫是对养禽业具有巨大危害的一类寄生原虫，其生活史各发育阶段的功能基因表达存在明显差异，解析这些表达差异的调控机制，是深入理解球虫发育、球虫与宿主相互作用以及新药开发的理论基础。基因组数据分析表明，球虫基因组缺乏DNA结合的顺式转录因子，而富含组蛋白修饰等相关蛋白酶的编码基因，提示表观遗传调控机制可能是球虫基因表达调控的主要方式，其中组蛋白去乙酰化酶是重要的基因表达调控因子。本研究以柔嫩艾美耳球虫组蛋白去乙酰化酶3（EtHDAC3）为研究对象，通过分析EtHDAC3的表达模式特征及酶活性的动力学，解析EtHDAC3功能复合体的组分，明确EtHDAC3调控基因表达的分子机理及其对球虫发育的作用。并通过HDAC抑制剂对EtHDAC3活性及球虫发育的影响，筛选在抗球虫药物上具有应用前景的EtHDAC3特效抑剂。研究结果有助于深入认识球虫基因表达调控的理论，对球虫病防治具有重要的理论意义。

中文关键词： 鸡球虫病；艾美耳球虫；组蛋白；组蛋白修饰；组蛋白去乙酰化酶

英文摘要： Eimeria spp., the pathogen of the poultry coccidiosis, is an absolute intracellular protozoan parasite belonging to Apicomplexa phylum. Coccidiosis is the most important disease affecting the poultry industry worldwide and control of the disease is presently based on managerial skills and the use of prophylactic coccidiostatic drugs. With the emergence of drug resistant Eimeria strains, emphasis has been laid on development of new drugs. Eimeria spp. has a monoxenous life cycle in which there are complicated developmental stage conversions involving dramatic gene expression changes. Understanding the mechanism of causing these expression changes is the central topic in research and drug development. As well as other Apicomplexa parasite, such as Toxoplasma gondii and Plasmodium falciparum, Eimeria genome lack the coding sequence for DNA-binding transcription factors, in contrast, the genome possess lots of histone modification enzymes. This gene distribution bias implicate a epigenetic regulatory mechanism,which is charged for the regulation of gene expression and stage conversions. Histone deacetylase (HDAC) plays an important role in epigenetic regulations,in addition,the HDAC inhibitors are potent molecules for drug development. In this study, we will focus on the Eimeria tenella histone deacetylase3 (EtHDAC3

英文关键词： Coccidiosis；Eimeria tenella；Histone；Histone modification；Histone deacetylase