Plasmodium Liver Stage Transcriptome
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PROVIDER: PRJEB23770 | ENA |
REPOSITORIES: ENA
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Project description:Plasmodium berghei transcriptome for female gametocytes, male gametocytes, and asexual erythrocytic stages
2017-08-21 | GSE102167 | GEO
Project description:Most malaria drug development focuses on parasite stages detected in red-blood cells even though to achieve eradication next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4,000 commercially available compounds with previously demonstrated blood stage activity (IC50 < 1 M-BM-5M), and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. Our orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 mg/kg) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms. Genome DNA from IP resistant strains vs. Reference 3D7 or Dd2
2011-10-31 | E-GEOD-32485 | biostudies-arrayexpress
Project description:Most malaria drug development focuses on parasite stages detected in red-blood cells even though to achieve eradication next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4,000 commercially available compounds with previously demonstrated blood stage activity (IC50 < 1 µM), and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. Our orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 mg/kg) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms.
2011-10-31 | GSE32485 | GEO
Project description:Many eukaryotic developmental and cell fate decisions are effected post-transcriptionally that mechanistically involve RNA binding proteins as regulators of translation of key mRNAs. In the unicellular eukaryote malaria parasite, Plasmodium, one of the most dramatic changes in cell morphology and function occurs during transmission between mosquito and human host. In the mosquito salivary glands, Plasmodium sporozoites are slender, motile and remain infectious for several weeks; only after transmission and liver cell invasion, does the parasite rapidly transform into a round, non-motile exo-erythrocytic form (EEF) that gives rise to thousands of infectious merozoites to be released into the blood stream. Here we demonstrate a Plasmodium homolog of the RNA binding protein, Pumilio, as a key regulator of the sporozoite to EEF transformation. In the absence of Pumilio-2 (Puf2) Plasmodium berghei sporozoites initiate early stage EEF development inside mosquito salivary glands with characteristic morphological changes; puf2- salivary gland sporozoites lose gliding motility, cell traversal ability and are less infective. Global expression profiling confirmed that transgenic parasites exhibit genome-wide transcriptional adaptations typical for Plasmodium intra-hepatic development. The data demonstrate that Puf2 is a key player in regulating developmental control, and imply that transformation of salivary gland-resident sporozoites into early liver stage parasites is regulated by a post-translational mechanism.
2010-11-01 | E-TABM-1067 | biostudies-arrayexpress
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.
2019-03-25 | PXD010559 | Pride
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
2016-04-08 | GSE80015 | GEO
Project description:To study the liver stage of the rodent malaria parasite Plasmodium berghei, we molecularly characterized thousands of infected and uninfected hepatocytes in different time points and inferred their spatial coordinates. Thus enabling us to characterize the host’s and parasite’s temporal expression programs in a zonally-controlled manner.
2022-08-31 | GSE181725 | GEO
Project description:The transmission of the malaria parasite between mosquitoes and mammals requires translational repression to ensure that only the proper proteins are expressed and correct folded at the right time, it will need for the next developmental stage.Due to their essential role for malaria transmission, gametocytes represent prime targets for transmission-blocking strategies intended to prevent spread of the deadly disease. In this study, we generate HspJ62 gene knockout line (ΔHspJ62) that is gametocyte non-producing lines. Transcriptional profiling of wild type Plasmodium berghei and genetic KO Hspj62 genes at single time points during erythrocytic parasite development.
2021-12-15 | GSE168974 | GEO
Project description:Phosphatase type 1 is a major enzyme essential to Plasmodium development. However, the detailed mechanisms underlying its regulation remain to be deciphered. In this work, we report the functional characterization of the Plasmodium berghei LRR1, an ortholog of SDS22, one of the most ancient and conserved Phosphatase type 1 (PP1) interactor. SDS22 has been described as a PP1 regulator essential to critical cellular features such as motility, polarity, epithelium integrity or mitosis completion. Our study shows that in Plasmodium berghei, PbLRR1 is expressed during the intra-erythrocytic developmental cycle and up to the zygote stage during sexual development. PbLRR1 can be found in complex with PbPP1 in both asexual and sexual stages and is able to inhibit the phosphatase activity. Then, genetic analysis demonstrated that PbLRR1 deletion affects the course of the parasite development during early sporogony which manifest by the production of fewer and smaller oocysts. Finally, PbLRR1 interactome analysis associated with phospho-proteomics studies led to the identification of several putative PbLRR1/PbPP1 substrates. Although previously unsuspected PP1 substrates, some of them have been characterized as essential to the parasite sexual development. In addition, and for the first time, we identify the PP1 inhibitor 3 as a substrate of the PP1/LRR1 complex. In summary, this study provides insights into previously unrecognized PbPP1 fine regulation of Plasmodium early sporogony development through its interaction with PbLRR1.
2022-10-14 | PXD030389 | Pride
Project description:During the malaria infection, Plasmodium parasites invade the host’s red blood cells where they can differentiate into two different life forms. The majority will replicate asexually and infect new erythrocytes. A small percentage, however, will transform into gametocytes – a specialized sexual stage able to survive and develop when taken up by Anopheles mosquito. As the gametocytes ensure the parasite’s transmission to a new host, their generation is an attractive target for new antimalarial interventions. The molecular mechanisms controlling gametocytogenesis, however, remain largely unknown due to the technical challenges: the early gametocytes are morphologically indistinguishable from asexual parasites and present in very low numbers during the infection. Recently, AP2-G - a transcription factor from an apicomplexa-specific apiAP2 family – was described as indispensable for gametocyte commitment in both human malaria parasite Plasmodium falciparum and rodent malaria model Plasmodium berghei. Therefore, we have decided to test whether the overexpression of this factor alone could increase gametocyte production and enable the investigation of uncharacterised, earliest stages of gametocyte development. To this end, we have engineered PBGAMi - a Plasmodium berghei line, in which all parasites were ap2-g deficient by default but able to overexpress it when induced with rapamycin. While the control parasites (PBGAMi R-), as expected, differentiated into asexual forms (schizonts) only, almost all rapamycin-treated parasites (PBGAMi R+) transformed into gametocytes. We used the generated line to perform RNA-seq analysis of the R- and R+ populations at different time points of their development and identify the changes arising between them, mapping the sequence of events leading to the formation of gametocytes.
2018-06-30 | GSE110201 | GEO