REGULATION OF MSP EXPRESSION IN LESHMANIA CHAGASI

本研究计划的长期目标是表征调节利什曼毒力因子gp63表达的机制。gp63的表达受发育调控，该蛋白酶在致病性原毛菌中表达水平最高。在chagasi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种不同的类型，它们的表达受发育调控。待验证的假设是，msp基因的表达是通过一种影响msp转录物稳定性的机制在转录后调节的。我们的研究将检验寄生虫的发育形式对三种msp基因转录本的表达和半衰期的影响。我们将尝试识别针对这些转录物降解的顺式和反式作用元件。这些研究可能提供对其他利什曼原虫毒力基因调控机制的见解，以及对这些生物中基因调控的更一般机制的见解。

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.