Project description:The purpose of this research is to identify and evaluate the global gene expression of the rodent malaria parasites Plasmodium yoelii, Plasmodium berghei and Plasmodium chabaudi blood-stage parasites and specifically compare the blood stage gene expression profiles of samples derived from previous studies on Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi
Project description:We have used cDNA microarrays to compare gene expression profiles in brains from normal mice to those infected with the Anka strain of Plasmodium berghei, a model of cerebral malaria. For each of three brains in each group, we computed ratios of all quantifiable genes with a composite reference sample and then computed ratios of gene expression in infected brains with untreated controls. Of the almost 12,000 unigenes adequateluy quantified in all arrays, about 3% were significantly downregulated (p<0.05, >50% fold change) and about 7% were upregulated. Upon inspection of the lists of regulated genes, we identified a high number encoding proteins of importance to normal brain function or associated with neuropathology. These results emphasize the important impact of malarial infection on gene expression in brain and provide tentative target biomarkers that might provide novel therapeutic targets for neurological sequelae of disease.
Project description:We use the Plasmodium berghei rodent model to characterize the proteome of the final phase of liver stage development, the merosomes, packets of hepatic merozoites that bud from the host hepatocyte to initiate the blood stage of malaria. Plasmodium berghei WT ANKA strain was used to infect HepG2 hepatoma cells. Samples were fractionated by strong cation exchange, and nano-LC Orbitrap mass spectrometry was used to perform untargeted proteomic profiling of 3 biological replicates. Data was processed using MaxQuant and LFQ. Additional searches were performed to identify peptides from cleaved acetylated PEXELs (protein export elements) to identify proteins putatively exported to the host hepatocyte during liver stage development.
Project description:Recent advances in high throughput sequencing methodologies allow the opportunity to probe in depth the transcriptomes of organisms including important human pathogens. In this project, we are using Illumina sequencing technology to analyze the transcriptome (RNA-Seq) of experimentally accessible stages of the mouse malaria parasite, P. berghei ANKA. The aim is to make transcriptional landscape maps of different life cycle stages of P. berghei ANKA at single base pairs resolution. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Project description:Proteomic characterization of complexity and dynamics of detergent resistant membranes of sexual and asexual stages of the rodent malaria parasite Plasmodium berghei
Project description:Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection, predominantly experienced by children and non-immune adults, which results in great mortality and long-term sequelae. Recent reports based on histology of post-mortem brain tissue suggest that CM may be the common end point for a range of syndromes. Here, we have analysed the gene expression profiles in brain tissue taken from experimental CM (ECM)-susceptible, Plasmodium berghei ANKA (PbA)-infected C57BL/6 (B6) and CBA/CaH (CBA) mice with ECM. Gene expression profiles were largely heterogeneous between the two ECM-susceptible strains. These results, combined with experimental data, support the existence of distinct pathogenic pathways in CM. Keywords: disease state analysis
