DESCRIPTION: (provided by the applicant): The advent of high-throughput methods for the analysis of global gene expression together with the Malaria Genome Project open up new opportunities for furthering our understanding of the fundamental biology and virulence of the malaria parasite. Serial analysis of gene expression (SAGE) is particularly well suited for malarial systems, as little is known about gene expression and the many of genes identified in the sequencing project are of unknown function. SAGE is an extremely powerful tool with which to simultaneously and quantitatively analyze mRNA transcript profiles from a given cell population, allowing for the discovery of new genes. For the first time, it is now possible to examine the response of all of the genes to stimuli such as drug treatment or immune pressure in vivo. Relating genomic sequence to function and ultimately to the biology is the next challenge. Work in other systems such as Saccharomyces cerevisiae and humans has demonstrated a multigenic response to changes in growth conditions, cell cycle changes, responses to drug treatment and in different cancers. Such patterns of gene expression have proven useful in identifying networks of genes under common control and led to the identification of novel pathways which can be exploited for drug and vaccine development. Such approaches allow for the functional analysis of new genes without prior knowledge of the identity. The goal of this work is to examine transcription in Plasmodium falciparum through the determination of which of the parasite's predicted 7000 genes are expressed at various stages of the parasite life cycle or under different conditions such as in the presence of drug or under immune pressure. This expression information will then be used to choose specific genes for further functional analysis and to identify networks or patterns of gene expression that will be useful in identifying elements which control transcription in Plasmodium falciparum. Results from this work will serve as a resource of the scientific community, both in term of functional analysis and in the identification of functions of new genes. These goals will be achieved the development and optimization of the Serial Analysis of Gene Expression (SAGE) technology for Plasmodium falciparum; identification of networks of gene expression and characterization of cis elements involved in response-specific transcriptional control and the use of gene expression profiles and networks to identify new targets for drug and vaccine development.