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Last Updated: 18/06/2024
Elucidation of the regulation mechanism of transcription factor activity that determines the exact timing of gene expression in red-eye malaria parasite
Objectives
The applicant identified PREBP, a factor that acts on the promoter of the gene pf1-cys-prx, which is expressed during the trophozoite stage of Plasmodium falciparum, to activate transcription, and through bioinformatics analysis, a novel factor A, which has a similar structure to PREBP, was identified. Identified. This study, regarding PREBP and factor A, clarified 1) the details of the protein modification that regulates the subcellular localization of the factor, and 2) the motifs common to the promoters of genes that the factors control, and investigated the effects of malaria parasites in erythrocyte parasites.
National Center for Global Health and Medicine (NCGM), Japan
The exact mechanism of gene expression control during the erythrocytic parasite stage of the malaria parasite, including the identity of the transcription factors responsible for it, has not been elucidated. The overall purpose of this research is to elucidate the transcriptional control mechanism that supports cell cycle progression during the phase. This year, in order to analyze the above two objectives this study classified by function the gene groups obtained by chromatin immunoprecipitation with PREBP as a symmetry and exhaustive ChIP-Seq by the next-generation sequencer, which was performed last year. As a result, 43% of erythrocyte surface antigen genes such as PfEMP1 and rifin, 8% of kinase/phosphatase genes, 6% of DNA/RNA binding protein genes, 5% of genes involved in lipid metabolism, and genes of other proteins with unknown functions were found. It was 38%, suggesting the possibility that PREBP regulates the expression of gene groups involved in the basis of growth, such as switching antigenic polymorphisms of protozoa and house keeping metabolism. In order to clarify whether the candidate gene is actually regulated by PREBP, a plasmid was created in which the luciferase gene was connected downstream of the promoter of the candidate gene, and a plasmid in which the PREBP expression cassette was inserted was introduced into cultured Plasmodium falciparum and luciferase assay was performed. As a result, PREBP was suggested to suppress gene expression in some rifin gene promoters.
Apr 2020 — Mar 2023
$38,109