Characterization of Plasmodium falciparum long non-coding RNAs and their roles in gene regulation

Malaria remains a major public health problem worldwide and partially due to our incomplete understanding ofthe biology of Plasmodium falciparum our progress towards eradicating the disease has stalled in recent years.Long non-coding RNAs (lncRNAs) have emerged as a key component of gene regulation in eukaryotesinfluencing both the transcription of genes and the stability and translation of mRNAs. While specific lncRNAshave been shown to regulate pathogenesis and parasite development we still lack a comprehensive perspectiveon the importance of lncRNAs in P. falciparum. Here we propose to use a combination of state-of-the-artgenomic and molecular approaches to examine the role of lncRNAs in gene regulation and their modes of action.First we propose to evaluate at the genome scale how lncRNAs influence the regulation of gene expression ofneighboring and distant genes using a suite of computational approaches and novel genomic assays. Second we will comprehensively examine the role of a new antisense lncRNA located downstream of ap2-g the genethat encodes a transcription factor that acts as the master regulator of sexual commitment in malaria parasites.To do this we will generate genetically modified parasite lines which modulate the levels of the ap2-g lncRNAusing a variety of molecular approaches and we will phenotypically characterize the resulting effects on bothasexual and sexual blood stage malaria parasite development. Overall the proposed analyses will provide novelinsights into the roles of lncRNAs in gene regulation in Plasmodium parasites. The results of this proposal willlay the foundation for future studies aimed at characterizing additional well-curated and developmentallyregulated P. falciparum lncRNAs.