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.
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