Putting theLeishmaniagenome to work: functional genomics by transposon trapping and expression profiling

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Abstract
Leishmaniaare important protozoan pathogens of humans in temperate and tropical regions. The study of gene expression during the infectious cycle, in mutants or after environmental or chemical stimuli, is a powerful approach towards understanding parasite virulence and the development of control measures. Like other trypanosomatids,Leishmaniagene expression is mediated by a polycistronic transcriptional process that places increased emphasis on post–transcriptional regulatory mechanisms including RNA processing and protein translation. With the impending completion of theLeishmaniagenome, global approaches surveying mRNA and protein expression are now feasible. Our laboratory has developed theDrosophilatransposonmarineras a tool for trappingLeishmaniagenes and studying their regulation in the form of protein fusions; a classic approach in other microbes that can be termed ‘proteogenomics’. Similarly, we have developed reagents and approaches for the creation of DNA microarrays, which permit the measurement of RNA abundance across the parasite genome. Progress in these areas promises to greatly increase our understanding of global mechanisms of gene regulation at both mRNA and protein levels, and to lead to the identification of many candidate genes involved in virulence.