Characterization of plasmodium falciparum long non-coding rnas and their roles in gene regulation

The National Institute of Allergy and Infectious Diseases (NIAID) awarded the University of Maryland, Baltimore $445,488 under the Allergy and Infectious Diseases Research program (CFDA 93.855) for a two-year project period from July 1, 2025 through June 30, 2027. This Project Grant supports scientific research to characterize long non-coding RNAs (lncRNAs) in Plasmodium falciparum and elucidate their roles in gene regulation. The research deliverables include comprehensive genome-scale analyses examining how lncRNAs influence gene expression of neighboring and distant genes, as well as detailed phenotypic characterization of genetically modified parasite lines designed to modulate lncRNA levels, particularly an antisense lncRNA located downstream of the AP2-G transcription factor that regulates sexual commitment in malaria parasites.

The project outputs will advance understanding of lncRNA mechanisms in malaria parasite development and establish a foundation for future investigations of developmentally regulated P. falciparum lncRNAs. This fundamental research supports NIAID's mission to improve public health and address disease mechanisms through investigator-initiated biomedical research focused on infectious diseases.

Abstract

Malaria remains a major public health problem worldwide and, partially due to our incomplete understanding of the 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 eukaryotes, influencing both the transcription of genes and the stability and translation of mrnas. While specific LNCRNAS have been shown to regulate pathogenesis and parasite development, we still lack a comprehensive perspective on the importance of LNCRNAS in P. Falciparum. Here, we propose to use a combination of state-of-the-art genomic 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 of neighboring 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 gene that 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 lncrna using a variety of molecular approaches and we will phenotypically characterize the resulting effects on both asexual and sexual blood stage malaria parasite development. Overall, the proposed analyses will provide novel insights into the roles of LNCRNAS in gene regulation in plasmodium parasites. The results of this proposal will lay the foundation for future studies aimed at characterizing additional well-curated, and developmentally regulated P. Falciparum LNCRNAS.