TRYPANOSOME MRNA SYNTHESIS BY GENE TRANSFER

人类和动物锥虫病具有重要的医学、兽医学和生物学意义。 经济后果。 利什曼病和锥虫病引起慢性 有时甚至是致命的疾病， 随着前往这些地区的旅行的增加，发达国家也是如此。 在 南美洲的T. cruzi是一种地方性心脏病 （恰加斯病）是导致死亡和残疾的重要原因。 不幸的是，目前所有锥虫的治疗方法 感染是昂贵的，潜在的毒性，必须管理， 很长时间需要新的治疗方法， 需要更深入地了解 巨体科 调查员的目的是制定一个 增加对寄生虫生长的了解， 锥虫生物学的方面，这可能证明适合更新，更 有效且便宜的治疗方法。 这笔赠款的具体目的是为了进一步了解 参与锥虫mRNA合成的调节信号。 事实上，我们对募集RNA的蛋白质一无所知 在这些医学上， 重要的原生生物 所有锥虫的一个典型遗传特征 是每个锥虫mRNA获得剪接前导序列的能力 (SL)从细胞核运输之前的序列。 无处不在的 剪接前导序列的性质表明，这种短RNA可能是 必需mRNA 新陈代谢. 我们计划利用现有的生化技术 探索与SL RNA基因相互作用的蛋白质的结构 启动子和直接SL RNA合成。 这些分析将 包括基因克隆和蛋白质功能研究，将有助于确定 锥虫实现这一点的特殊机制 基本的细胞过程

The human and animal trypanosomiases have major medical, veterinary, and economic consequences. Leishmaniasis and trypanosomiasis cause chronic and sometimes fatal diseases in people in both developing countries and, as travel to these areas increases, in the developed world as well. In areas of South America where T. cruzi is endemic, heart disease (Chagas)is a signification cause of death and disability. Unfortunately, currently available treatments for all trypanosome infections are expensive, potentially toxic and must be administered for long periods of time. New therapeutic approaches are needed and will require a deeper understanding of the molecular biology of the tgrypanosomatidae. The aim of the investigator is to develop an increased knowledge of parasite growth in order to pinpoint vulnerable aspects of trypanosome biology, which may prove amenable to newer, more efficacious, and less expensive therapies. The specific aim of this grant is to further our understanding of the regulatory signals involved in mRNA synthesis in trypanosomes. Virtually nothing is known about the proteins that recruit RNA polymerases to DNA to initiation transcription in these medically important protists. A characteristic genetic trait of all trypanosomes is the ability of every trypanosomal mRNA to acquire a spliced leader (SL) sequence prior to transport from the nucleus. The ubiquitous nature of the spliced leader indicates that this short RNA may be essential in mRNA metabolism. We plan to use established biochemical techniques to explore the structure of proteins that interact with the SL RNA gene promoter and direct SL RNA synthesis. These analyses, which will include gene cloning and protein function studies, will help identify the specific mechanisms that trypanosomes employ to accomplish this fundamental cellular process.