Transcription profiling of Plasmodium yoeli yir multi-gene family in colonal populations
Ontology highlight
ABSTRACT:
ORGANISM(S): Plasmodium yoelii
SUBMITTER: Celine Carret
PROVIDER: E-TABM-537 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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.
2011-04-25 | E-MTAB-636 | biostudies-arrayexpress
Project description:Malaria remains a global health issue requiring the identification of novel therapeutic targets to combat drug resistance. Metabolic serine hydrolases are druggable enzymes playing essential roles in lipid metabolism. However, very few have been investigated in malaria-causing parasites. Here, we used fluorophosphonate broad-spectrum activity-based probes and quantitative chemical proteomics to annotate and profile the activity of more than half of predicted serine hydrolases in P. falciparum across the erythrocytic cycle. Using conditional genetics, we show that the activities of four serine hydrolases, previously annotated as essential (or important) in genetic screens, are actually dispensable for parasite replication. Importantly, we also identified eight human serine hydrolases that are specifically activated at different developmental stages. Chemical inhibition of two of them blocks parasite replication. This strongly suggests that parasites co-opt the activity of host enzymes and opens a new drug development strategy against which the parasite is less likely to develop resistance.
2022-10-14 | PXD035891 | Pride
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. chabaudi AS. The aim is to analyse cir gene expression during Plasmodium chabaudi infection and determine whether host genetic background can influence cir expression. 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/. Abstract: Transcriptome sequencing of blood stage P. chabaudi AS parasites grown under different host genetic backgrounds.
2011-11-03 | E-ERAD-25 | biostudies-arrayexpress
Project description:K13 mutations are causal for artemisinin resistance in Plasmodium falciparum human malaria. We characterized changes in protein abundance associated with K13 mutations during the parasite's 48h intra-erythrocytic developmental cycle by comparing protein expression profiles of K13 mutant (C580Y, R539T) and isogenic wild-type lines that were generated by zinc finger nuclease (ZFN) based editing in a laboratory-adapted clinical isolate (Cam3.II). For each parasite line, we harvested tightly synchronized ring and trophozoite parasites on two independent occasions, except for the C580Y line which was harvested only once at trophozoite stage.
2020-11-23 | PXD019612 | Pride
Project description:The process of erythrocyte invasion by merozoites of Plasmodium falciparum involves multiple steps, including the formation of a moving junction characterized by the redundancy of many of the receptor-ligand interactions involved. Several of the parasite proteins that interact with erythrocyte receptors or participate in other steps of the process of invasion are encoded by small subtelomerically-located multigene families of four to seven members. We report here that members of the multigene families pfRh, eba, rhopH1/clag and acbp exist in either an active or a silenced state. In the case of two members of the rhopH1/clag family, clag3.1 and clag3.2, expression was mutually exclusive. Silencing occurred in the absence of detectable DNA alterations, suggesting that it is transmitted epigenetically. This was unambiguously demonstrated for eba-140, which was silenced by the formation of facultative heterochromatin. Our data demonstrate that variant expression, epigenetic silencing and mutually exclusive expression in Plasmodium are not unique to genes encoding proteins exported to the surface of the erythrocyte like var genes but also occur for genes involved in host cell invasion..
2007-11-26 | E-SGRP-9 | biostudies-arrayexpress
Project description:Two mice per group were infected with one million purified schizonts from the WT and two clones (B3 and D1) of the pyhmgb2 KO lines. Parasitemia reached 10 to 20 % and equivalent gametocytemia total RNA was extracted from the WT and the B3 and D1 clones of the KO parasite lines using the Trizol method on saponin lysed of parasites. Four samples analysed including dye-swap
2008-04-19 | E-GEOD-9952 | biostudies-arrayexpress
Project description:RNA-binding proteins, such as DOZI/CITH and Puf2, have been shown to play critical roles in the life cycle in Plasmodium species. One of the characterized functions of these RNA-binding proteins is to bind to mRNAs and regulate their fates, and it is hypothesized that this regulation of mRNA homeostasis of specific transcripts is important for successful infection of both vectors and hosts by these parasites. To further understand the role that other RNA-binding proteins may play in translational repression and other critical processes in the parasite, we investigated ALBA4, another RNA-binding protein implicated in translational repression. We appended a C-terminal GFP-tag to ALBA4 (ALBA4::GFP), and then performed immunoprecipitations on chemically cross-linked samples using Streptavidin-coated beads coated with a biotin-conjugated anti-GFP antibody to capture the ALBA4 complex(es). We performed these experiments in multiple life cycle stages, including sexual stages (gametocytes) and asexual stage (schizonts). In gametocytes, we determined that ALBA4 associates with translational repression machinery. This is also the case in schizonts, however ALBA4 also associates with complexes involved in active translation, mRNA export, and mRNA degradation. We hypothesize that ALBA4 plays a multi-faceted role in mRNA homeostasis by associating with multiple protein complexes in a stage-specific manner.
2017-08-28 | PXD004183 | Pride
Project description:During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes M-bM-^@M-^S sexual stage precursor cells M-bM-^@M-^S likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the blood stream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood. We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and ~30 hours post invasion and mature gametocytes after around 7 days post invasion. We used 164/TdTom, a transgenic parasite line expressing a red fluorescent protein reporter under a gametocyte-specific promoter to generate schizont samples. Schizonts were subsequently isolated from both the fluorescent and non-fluorescent population by FACS and prepared for microarray analysis. Two biological replicates were produced for both the fluorescent and the non-fluorescent samples.
2015-01-13 | E-GEOD-64887 | biostudies-arrayexpress
Project description:Cerebral Malaria (HCM) is a serious neurological complication caused by Plasmodium falciparum infection. Currently the only treatment for HCM is the provision of anti-malarial drugs; however, such treatment by itself often fails to prevent death or development of neurological sequelae. To identify new potential adjunct treatments for HCM, we performed a non-biased whole brain transcriptomic time-course analysis of anti-malarial drug chemotherapy of murine experimental CM (ECM).
2018-07-03 | E-MTAB-6474 | biostudies-arrayexpress
Project description:Background: Host iron deficiency is protective against severe malaria as the human malaria parasite Plasmodium falciparum depends on free iron from its host to proliferate. Due to the absence of transferrin, ferritin, ferroportin, and a functional heme oxygenase, the parasite’s essential pathways of iron acquisition, storage, export, and detoxification differ from those in humans and may thus be excellent targets for therapeutic development. However, the proteins involved in these processes in P. falciparum remain largely unknown. Experimental design: To identify iron-regulated mechanisms and putative iron transporters in the human malaria parasite Plasmodium falciparum 3D7, we carried out whole-transcriptome profiling using bulk RNA-sequencing. The parasites were cultured either using erythrocytes from a donors with high, medium (healthy) or low iron status (experiment 1); or with red blood cells from another healthy donor in the presence or absence of 0.7 µM hepcidin, a specific ferroportin inhibitor and iron-regulatory hormone (experiment 2). This concentration of hepcidin was reported to reduce binding of ferrous iron to ferroportin by 50% in vitro (39). Samples from three biological replicates each were harvested at the ring and trophozoite stage (6 – 9 and 26 – 29 hours post invasion, hpi) during the second intra-erythrocytic developmental cycle under the conditions specified.
2024-04-08 | E-MTAB-13411 | biostudies-arrayexpress