MECHANISM OF ANTIGENIC VARIATION IN TRYPANOSOMA BRUCEI

布氏锥虫抗原变异机制

• 批准号: 3132140
• 负责人: Keith M. Gottesdiener
• 金额: $ 35.58万
• 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 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3132140
• 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

项目成果

Binding of trans-acting factors to the double-stranded variant surface glycoprotein (VSG) expression site promoter of Trypanosoma brucei.

反式作用因子与布氏锥虫双链变异表面糖蛋白（VSG）表达位点启动子的结合。

• DOI: 10.1016/s0166-6851(97)00094-7
• 发表时间: 1997
• 期刊: Molecular and biochemical parasitology
• 影响因子: 1.5
• 作者: Pham,VP;Rothman,PB;Gottesdiener,KM
• 通讯作者: Gottesdiener,KM

Transcription of the heat shock 70 locus in Trypanosoma brucei.

布氏锥虫热休克 70 位点的转录。

• DOI: 10.1016/0166-6851(90)90185-o
• 发表时间: 1990
• 期刊: Molecular and biochemical parasitology
• 影响因子: 1.5
• 作者: Lee,MG;VanderPloeg,LH
• 通讯作者: VanderPloeg,LH

Maturation of polycistronic pre-mRNA in Trypanosoma brucei: analysis of trans splicing and poly(A) addition at nascent RNA transcripts from the hsp70 locus.

布氏锥虫中多顺反子前体 mRNA 的成熟：分析 hsp70 基因座新生 RNA 转录物的反式剪接和 Poly(A) 添加。

• DOI: 10.1128/mcb.11.6.3180-3190.1991
• 发表时间: 1991
• 期刊: Molecular and cellular biology
• 影响因子: 5.3
• 作者: Huang,J;vanderPloeg,LH
• 通讯作者: vanderPloeg,LH

Characterization of a cDNA encoding a cysteine-rich cell surface protein located in the flagellar pocket of the protozoan Trypanosoma brucei.

编码位于原生动物布氏锥虫鞭毛袋中富含半胱氨酸的细胞表面蛋白的 cDNA 的表征。

• DOI: 10.1128/mcb.10.9.4506-4517.1990
• 发表时间: 1990
• 期刊: Molecular and cellular biology
• 影响因子: 5.3
• 作者: Lee,MG;Bihain,BE;Russell,DG;Deckelbaum,RJ;VanderPloeg,LH
• 通讯作者: VanderPloeg,LH

Evidence for segmental gene conversion between a cognate hsp 70 gene and the temperature-sensitively transcribed hsp70 genes of Trypanosoma brucei.

布氏锥虫同源 hsp 70 基因与温度敏感转录 hsp70 基因之间片段基因转换的证据。

• DOI: 10.1016/0166-6851(90)90184-n
• 发表时间: 1990
• 期刊: Molecular and biochemical parasitology
• 影响因子: 1.5
• 作者: Lee,MG;Polvere,RI;VanderPloeg,LH
• 通讯作者: VanderPloeg,LH