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.
