Plasmodium berghei transcriptome for female gametocytes, male gametocytes, and asexual erythrocytic stages
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ABSTRACT:
ORGANISM(S): Plasmodium berghei ANKA
PROVIDER: GSE102167 | GEO | 2017/08/21
REPOSITORIES: GEO
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Project description:The inner membrane complex (IMC), a double-membrane organelle underneath the plasma membrane in apicomplexan parasites, plays a significant role in motility and invasion and confers shape to the cell. We characterized the function of PbIMC1g, a component of the IMC1 family member in Plasmodium berghei. PbIMC1g is recruited to the IMC in late schizonts, activated gametocytes, and ookinetes. Pairwise yeast two-hybrid assays demonstrate that PbIMC1g interacts with IMC1c, a component of the PHIL1 complex, and the core sub-repeat motif ‘EKI(V)V(I)EVP’ in PbIMC1g is essential for this interaction. Localization of PbIMC1g to the IMC was dependent on its IMCp domain, while its C-terminus and palmitoylation sites were required for the full efficiency of proper IMC targeting. PbIMC1g is required for asexual stage development, and its conditional knockdown resulted in a defect in schizogony. Additionally, PbIMC1g was also important for male gametogenesis and ookinete development. As an IMC component that assists in anchoring the glideosome to the subpellicular network, PbIMC1g was also involved in ookinete motility and mosquito midgut invasion. IMC1g from the human parasite P. Plasmodium vivax could functionally replace PbIMC1g in P. berghei, confirming the evolutionary conservation of IMC1g proteins in Plasmodium spp. Together, this work reveals an essential role of IMC1g in the parasite life cycle and suggests that IMC1 family members likely contribute to parasite gliding and invasion.
2024-11-06 | GSE269994 | GEO
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
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. At the same time we have generated purified transcriptomes of male and female gametocytes for the reference
2021-03-13 | GSE168817 | GEO
Project description:Transcriptional profiling of gametocyte non-producer lines in Plasmodium berghei Transcriptome of gametocyte non producer lines (natural and genetic KO) and parental (820) lines. The aim of the study was to identify key genes involved in the decision to commit to gametocytogenesis in Plasmodium berghei. These microarrays compare naturally selected lines that do not produce gametocytes, and the parental line and additionally a genetic knock out of AP2-G PBANKA_143750. Data published Sinha, Hughes, et, al Nature tbc.
2013-12-13 | GSE53246 | GEO
Project description:Gametocytogenesis and gametogenesis in malaria parasites are complex processes of cell differentiation and development likely involving many gene products. Gametocytes develop in the blood of the vertebrate host but mature gametocytes are not activated until taken up by the mosquito vector. Several distinct mutants have been described that block gametogenesis but the detailed molecular causes for the mutant phenotypes are not understood. To investigate whether a block in gametogenesis also results in a changed transcriptional profile, we studied two gene deletions mutants; act2(-) lacking stage-specific actin II and CDPK4(-) lacking calcium-dependent protein kinase 4. Whole-genome microarray analysis was performed from RNA of mature gametocytes to compare the transcriptomes of the mutants with wild-type Plasmodium berghei. The microarray analysis identified ~12% of all genes being differentially expressed in either or both mutants compared to normal gametocytes, as defined by at least two-fold change in transcript abundance. A large proportion of differentially expressed genes in both mutants overlapped consistent with the developmental gametocyte arrest. Distinct profiles in each mutant were also observed. Microarray experiments were performed as dual-color hybridizations on Agilent-024169 custom whole genome Plasmodium berghei 44K arrays. To compensate for dye-specific effects, a dye-reversal color-swap was applied.
2015-09-15 | E-GEOD-65032 | biostudies-arrayexpress
Project description:Plasmodium falciparum asexual parasites and late gametocytes were treated for 24 or 48 h with MMV390048 or MMV642943 in order to understand the functional consequences of inhibiting lipid kinases
2017-07-01 | GSE100692 | GEO
Project description:Transcriptional profiling of gametocyte non-producer lines in Plasmodium berghei Transcriptome of gametocyte non producer lines (natural and genetic KO) and parental (820) lines. The aim of the study was to identify key genes involved in the decision to commit to gametocytogenesis in Plasmodium berghei. These microarrays compare naturally selected lines that do not produce gametocytes, and the parental line and additionally a genetic knock out of AP2-G PBANKA_143750. Data published Sinha, Hughes, et, al Nature tbc. 2- colour microarray comparing to common background pool (containing all life cycle stages). Replicates of different life cycle stages of gametocyte non-producer lines and wild tye (WT) parental control lines
2013-12-13 | E-GEOD-53246 | biostudies-arrayexpress
Project description:The essential and distinct functions of Protein Phosphatase type 1 (PP1) catalytic subunit in eukaryotes are exclusively achieved through its interaction with a myriad of regulatory partners. In this work, we report the molecular and functional characterization of Gametocyte EXported Protein 15 (GEXP15), a Plasmodium specific protein, as a regulator of PP1. In vitro interaction studies demonstrated that GEXP15 physically interacts with PP1 through the RVxF binding motif in P. falciparum and P. berghei. Functional assays showed that GEXP15 was able to increase the PP1 activity and the mutation of the RVxF motif completely abolished this regulation. Immunoprecipitation assays of tagged GEXP15 or PP1 in P. berghei followed by immunoblot or mass spectrometry analyses confirmed their interaction and showed that they are present both in schizont and gametocyte stages in shared protein complexes involved in the spliceosome and proteasome pathways and known to play essential role in parasite development. Phenotypic analysis of viable GEXP15 deficient P. berghei blood parasites showed that they were unable to develop lethal infection in BALB/c mice or to establish experimental cerebral malaria in C57BL/6 mice. Further, although deficient parasites produced gametocytes they did not produce any oocysts/sporozoites indicating a high fitness cost in the mosquito. Global proteomic and phosphoproteomic analyses of GEXP15 deficient schizonts revealed a profound defect with a significant decrease in the abundance and an impact on phosphorylation status of proteins involved in regulation of gene expression or invasion. Moreover, the depletion of GEXP15 seemed to impact mainly the abundance of some specific proteins of female gametocytes. Our study provides the first insight into the contribution of a PP1 regulator to Plasmodium virulence and suggests that GEXP15 affects both the asexual and sexual life cycle.
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Project description:Proteomic characterization of complexity and dynamics of detergent resistant membranes of sexual and asexual stages of the rodent malaria parasite Plasmodium berghei
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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.
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