Project description:To investigate the artemisinin resistance mechanism, we conducted a systematical evaluation of histone acetyltransferase expression in 45 cloned P. falciparum parasites and 30 wild-type field isolates. Remarkably, PfMYST, a member of the histone acetyltransferase MYST family, emerged as the sole candidate significantly associated with prolonged ring-survive of parasites. WGS analysis confirmed the genomic consistency among different parasite subclones. CHIP-seq analysis revealed PfMYST’s pivotal role in mediating histone modifications, particularly in H4K5ac and H4K8ac, within the P. falciparum genome. Through single-cell RNA sequence and conditional knockdown approaches, we identified and functionally validated PfMYST-targeted genes contributing to Plasmodium’s adaptive artemisinin resistance.
Project description:Transcriptomic Analysis of Cultured Sporozoites of P. falciparum RNA-seq reads from each of three developmental stages (2 replicates per sample) were mapped to the reference Plasmodium falciparum genome, and gene expression levels were calculated for each sample.
Project description:Epigenetic mechanisms have been poorly understood in Plasmodium falciparum, the causative agent of malaria. To elucidate stage specific epigenetic regulations in P. falciparum, we performed genome-wide mapping of various histone modifications, nucleosomes and RNA Polymerase II. Our comprehensive analysis suggest that transcription initiation and elongation are distinct in Plasmodium. In this study, by analyzing histone modifications, nucleosome occupancy and RNA Polymerase II (Pol II) at three different IEC developmental stages of Plasmodium; ring, trophozoite and schizont, we tried to unravel the epigenetic mechanism associated with gene regulation. Examination of H3K27me3, H3K4me3, H3K9me3, H3K14ac, H3K4me1, H3K79me3, H3K27ac, H3K4me2, H3K9ac, H4ac, RNA Pol II and Histone H3 at three different stages of Plasmodium falciparum