自然和人工诱导布氏锥虫分化的分子机理

项目名称： 自然和人工诱导布氏锥虫分化的分子机理

项目编号： No.31472058

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 动物学

项目作者： 伦照荣

作者单位： 中山大学

项目金额： 89万元

中文摘要： 布氏锥虫是人睡眠病和动物锥虫病的病原体，是WHO和OIE致力要在全球控制的重要人畜共患热带病病原体之一，也是国际学术界研究宿主与寄生原虫相互关系的重要模式物种。药物治疗锥虫病目前仍是WHO优先选择的方法之一，但由于长期使用为数不多的几种抗锥虫药，许多流行区虫株已对其出现严重的抗性，导致治疗失败。布氏锥虫从分裂的细长型分化成没有分裂能力的粗短型是其传播的关键，也是其生活史在哺乳动物和人中最薄弱的环节。尽管人们对锥虫的分化包括人工诱导分化作了大量的研究，但其精确机理迄今未明。本项目拟在自然和人工诱导的条件下，对布氏锥虫从细长型分化成粗短型的编码和非编码RNA的转录组进行大规模测序分析，通过基因剔除和RNAi技术明确诱导布氏锥虫分化的关键分子和相关基因及其功能，为研究针对诱导锥虫分化的新型药物的研发提供全新的理论基础。

中文关键词： 布氏锥虫；基因功能；比较基因组学；转录组；分子机理

英文摘要： Trypanosoma brucei is the pathogen of human sleeping sickness and animal Nagana disease. This parasite is one of the most important tropical zoonotic pathogens which are strongly required to be controlled and eliminated around the world by WHO. In addition, T. brucei is also one of the well-known and well investigated parasitic organisms particularly in the relationship between host and parasite. Similar to other eukaryotic pathogens, because of the lack of vaccine, chemotherapy is still the key step for the control of sleeping sickness and Nagada disease as well as other animal trypanosomiasis in the endemic regions. However,the long term use of a few compounds has resulted in strong resistance to these compounds and caused less effective for treatment. It is well known that the differentiation of T. brucei from dividing slender to non-dividing stumpy forms is the key stage for infection and transmssion to insect vector. It is also an idea targeting stage for control. Although lot of work have been done on the differentiaton of T. brucei based on the natural and artifical conditions, little is known regaring the molecular mechanism of differentiation of this parasite from slender to stumpy forms. Here, we are planning to sequence and compare the transcriptomes of coding and non-coding RNA of T. brucei before and after differentiation in natural and artifical treatment and to identify the key factors and related genes which are linked to the differentiation. Data from this project will be greatly benefitted for understading the molecular mechanism of differentiation of T. brucei and will provide valuable molecular information to develop the new drugs for against trypanosomiasis in human and animals.

英文关键词： Trypanosoma brucei;gene function;comparative genomic;transcriptome;molecular mechanism