Project description:We infected wild type and Elf4 deficient mice with Plasmodium yoelii 17XNL, a non-lethal species, to investigate and compare anti-Plasmodium response of two groups of mice.
Project description:We infected wild type and Elf4 deficient mice with Plasmodium yoelii 17XNL, a non-lethal species, to investigate and compare anti-Plasmodium response of two groups of mice.
Project description:Plasmodium yoelii YM asexual blood stage parasites express multiple members of the py235 gene family, part of the super-family of genes including those coding for Plasmodium vivax reticulocyte binding proteins and Plasmodium falciparum RH proteins. Dr Tony Holder's laboratory (NIMR, London) has been successful in deleting one of the RH family genes (Py01365) by transfection and insertion of the TgDHFR gene, and cloned the resulting parasite in YM background. The gene expression patterns of the mutant parasite line were compared to that of the wild type YM parasite.
Project description:The liver stage of the etiological agent of malaria, Plasmodium, is obligatory for successful infection of its various mammalian hosts. Differentiation of the rod-shaped sporozoites of Plasmodium into spherical exoerythrocytic forms (EEFs) via bulbous expansion is essential for parasite development in the liver. However, little is known about the host factors regulating the morphological transformation of Plasmodium sporozoites in this organ. Here, we show that sporozoite differentiation into EEFs in the liver involves protein kinase Cζ-mediated NF-κB activation, which robustly induces the expression of C-X-C chemokine receptor type 4 (CXCR4) in hepatocytes and subsequently elevates intracellular Ca2+ levels, thereby triggering sporozoite transformation into EEFs. Blocking CXCR4 expression by genetic or pharmacological intervention profoundly inhibited the liver stage development of the P. berghei rodent malaria parasite and the human P. falciparum parasite also. Collectively, our experiments show that CXCR4 is a key host factor for Plasmodium development in the liver, and CXCR4 warrants further investigation for malaria prophylaxis.
Project description:To determine the role of ALBA4 in mRNA homeostasis in Plasmodium parasites, we performed comparative total RNA-seq between a WT-GFP line and an alba4-null line. We performed these experiments at three points in the life cycle - asexual (schizont), sexual (gametocyte), and oocyst sporozoite stages. We found that ALBA4 has a multi-faceted role in mRNA homeostasis, and is involved in mRNA fate determination. ALBA4 appears to act in a stage-specific manner, affecting different sets of transcripts in each stage. Our data suggests that ALBA4 plays opposing roles - possibly promoting degradation in schizonts, while promoting mRNA protection in gametocytes. In oocyst sporozoites, it appears that ALBA4 has a mixed role, and may be involved in both degradation and protection of mRNAs.
