REGULATION OF MSP EXPRESSION IN LESHMANIA CHAGASI

查加斯利什曼原虫 MSP 表达的调控

• 批准号: 2862567
• 负责人: ANDREW BRITTINGHAM
• 金额: $ 1.56万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-11-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2862567
• 关键词: Leishmania; circumsporozoite protein; densitometry; developmental genetics; gene expression; genetic regulation; genetic regulatory element; glycoproteins; northern blottings; nuclear runoff assay; polymerase chain reaction; posttranscriptional RNA processing; protein degradation; protein structure function; regulatory gene; southern blotting; virulence

The long term objective of this research proposal is to characterize the mechanism(s) regulating the expression of the Leishmania virulence factor gp63. The expression of gp63 is developmentally regulated and the protease is expressed at its highest level on virulent promastigotes. In Leishmania chagasi, the gene family encoding gp63 (msp) is comprised of at least 18 tandem genes per haploid genome. These genes can be classified into three distinct classes whose expression is developmentally regulated. The hypothesis to be tested is that the expression of msp genes is regulated post-transcriptionally through a mechanisms which affects the stability of msp transcripts. Our studies will examine the affect of the developmental form of the parasite on the expression and half-life of transcripts from each of the three classes of msp genes. We will attempt to identify cis and trans- acting elements which target these transcripts for degradation. These studies may provide insight into the mechanisms by which other Leishmania virulence genes are regulated as well as provide insight into more general mechanisms of gene regulation in these organisms.

本研究计划的长期目标是表征调节利什曼原虫毒力因子gp63表达的机制。 gp63的表达受发育调控，并且蛋白酶在毒性前鞭毛体上以其最高水平表达。 在恰加斯利什曼原虫中，编码gp63（msp）的基因家族由每个单倍体基因组至少18个串联基因组成。 这些基因可以分为三个不同的类，其表达是发育调控。 待检验的假设是，msp基因的表达是通过影响msp转录物稳定性的机制在转录后调节的。 我们的研究将检查寄生虫的发育形式对三类msp基因中每一类的转录本的表达和半衰期的影响。 我们将试图确定顺式和反式作用元件的目标，这些转录降解。 这些研究可能提供了深入了解其他利什曼原虫毒力基因的调节机制，以及提供更一般的机制，在这些生物体中的基因调控的见解。