STAGE-SPECIFIC GENES IN LEISHMANIA ENRIETTII

Leishmania parasites are the causative agents of leishmaniasis, a
disease that affects large numbers of people over vast regions of
the globe. There are two principal stages in the life cycle of
these parasitic protozoa: promastigotes are slender, flagellated,
extracellular organisms that live in the gut of the sandfly vector,
while amastigotes are oval, non-flagellated, sessile, intracellular
parasites that are specifically adapted for growth and survival
within the mammalian host macrophages. Each of these two
stages of the life cycle expresses a subset of stage-specific genes
that confer a distinct phenotype upon that stage. The purpose of this proposal is to study the genes that encode
three previously identified stage-specific proteins. The RNAs
encoding two of these proteins are very abundant in the
promstigote stage but are absent in amastigotes; the RNA
encoding the third protein is abundant in amastigotes but absent
in promastigotes. We will clone the genes encoding these three
stage-specific proteins and use these cloned genes to: i)
understand the molecular mechanisms responsible for repressing
their expression in one life-cycle stage and inducing their
expression in the other stage, and ii) probe the function of each
stage-specific protein in the parasite life cycle. These studies on stage-specific gene expression will contribute to
two long-term objectives: i) to understand basic features of gene
expression and regulation in these parasites, phenomena which are
poorly understood at present; ii) to understand how these parasites
adapt to and survive within two different and potentially hostile
environments, the insect gut and the host macrophage.