MECHANISM OF ANTIGENIC VARIATION IN TRYPANOSOMA BRUCEI

布氏锥虫抗原变异机制

• 批准号: 3132138
• 负责人: L H T VAN DER PLOEG
• 金额: $ 32.9万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3132138
• 关键词: DNA directed RNA polymerase; Trypanosoma; biological polymorphism; chromosome translocation; gene expression; gene mutation; genetic manipulation; genetic recombination; genetic transcription; genome; glycoproteins; immunogenetics; laboratory mouse; laboratory rabbit; laboratory rat; membrane activity; membrane proteins; microorganism genetics; microorganism immunology; molecular cloning; molecular genetics; mutant; nucleic acid probes; nucleic acid sequence; parasitic disease chemotherapy; protozoal antigen; trypanosomiasis

Trypanosomes and related protozoan parasites cause a range of diseases man and his livestock (e.g. Chagas disease and sleeping sickness). The blood-dwelling parasite Trypanosoma brucei escapes immune-destruction through antigenic variation, by periodically changing the production of one variant cell surface glycoprotein (VSG) coat to the next. We will study the genetic basis of immune- evasion. The focus will be on transcriptional control of VSG genes and on understanding the importance of expression site, chromosome and nuclear structure for VSG gene activation. We will also study the biological role of expression site associated genes, that are coordinately transcribed with the VSG gene. We are particularly interested in transcription of VSG genes by a novel type of RNA polymerase that is insensitive to the drug alpha- amanitin. We will characterize this RNA polymerase and compare its transcriptional specificity to that of other eukaryotic RNA polymerases. We will test drugs for their capability to interfere with transcription switching of VSG genes. We will survey the importance of transcription of protein-coding genes by alpha- amanitin insensitive RNA polymerases in trypanosomes and related kinetoplastida. These studies are aimed at understanding the biological role of transcription of protein coding get by RNA polymerase II and another as yet unidentified RNA polymerase. A rationale for drug therapy may result. To facilitate the molecular analysis of these protozoan parasites will further develop a DNA transfection system for T.brucei. We will construct vectors that can be used to introduce foreign genes into trypanosomes. The vectors will be engineered to resemble VSG gene expression sites with which chromosomal rearrangements and transcript control of VSG genes will be studied.

锥虫和相关的原生动物寄生虫引起一系列的 疾病的人和他的牲畜（例如恰加斯病和睡眠 病）。 血液寄生虫布氏锥虫 通过抗原变异，通过周期性 改变一种变异细胞表面糖蛋白的产生 (VSG)外套到下一个 我们将研究免疫的遗传基础- 逃避 重点将放在VSG基因的转录控制 以及对表达位点、染色体 和细胞核结构来激活VSG基因。 我们还将研究 表达位点相关基因的生物学作用， 与VSG基因协同转录。 我们特别感兴趣的是VSG基因的转录， 一种新型的RNA聚合酶，对药物α- 鹅膏毒肽 我们将描述这种RNA聚合酶的特征， 它对其他真核RNA的转录特异性 聚合酶 我们将测试药物的干扰能力 VSG基因的转录转换。 我们将调查 蛋白质编码基因转录的重要性 锥虫和相关的鹅膏蕈碱不敏感的RNA聚合酶 动质体 这些研究旨在了解 RNA编码蛋白质转录的生物学作用 聚合酶II和另一种尚未鉴定的RNA聚合酶。 一 可能导致药物治疗的合理性。 为了便于对这些原生动物寄生虫进行分子分析 将进一步发展布氏锥虫的DNA转染系统。 我们 将构建可以用于导入外源基因的载体 变成锥虫 载体将被设计成类似于VSG 基因表达位点，染色体重排和 将研究VSG基因的转录调控。