BIOLOGICAL VARIATION AMONG AFRICAN TRYPANOSOMES

非洲锥虫是人类昏睡病的病原体 以及其他动物的致命性疾病。不同物种间的生物变异 基因相关的非洲锥虫是这一主题的中心 提议，主要集中在毒性上。提出了这个假说 非洲锥虫调节毒力的克隆性表达 在哺乳动物宿主感染过程中通过差异表达 特定的基因。拟议研究的实验基础 包括一种具有良好特征和临床相关性的布鲁氏锥虫 罗德森毒力模型系统，以及一组不同的 从高毒力锥虫和低毒力锥虫克隆的表达基因。在这 建议，将选择与毒力相关的候选基因并 测试特定毒力的功能和遗传联系 表型。结果将提供有关以下方面的新的相关信息 锥虫细胞生物学及其可能导致的致病机制 治疗或控制锥虫病的新途径。

African trypanosomes are the causative agents of human sleeping sickness as well as fatal disease in other animals. Biological variation among genetically related African trypanosomes is the central theme of this proposal, with the primary focus on virulence. The hypothesis addressed is that African trypanosomes regulate the clonal expression of virulence during infection of a mammalian host by differential expression of specific genes. The experimental foundation for the proposed studies includes a well characterized and clinically relevant Trypanosoma brucei rhodesiense model system of virulence, and a panel of differentially expressed genes cloned from high and low virulence trypanosomes. In this proposal, candidate virulence-associated genes will be selected and tested for functional and genetic linkages to specific virulence phenotypes. The results will provide new and relevant information on trypanosome cell biology and mechanisms of pathogenesis that may lead to new avenues for treatment or control of trypanosomiasis.