A Comprehensive Survey of the
            <i>Plasmodium</i>
            Life Cycle by Genomic, Transcriptomic, and Proteomic Analyses

Hall, Neil; Karras, Marianna; Raine, J. Dale; Carlton, Jane M.; Kooij, Taco W. A.; Berriman, Matthew; Florens, Laurence; Janssen, Christoph S.; Pain, Arnab; Christophides, George K.; James, Keith; Rutherford, Kim; Harris, Barbara; Harris, David J.; Churcher, Carol; Quail, Michael A.; Ormond, Doug; Doggett, Jon; Trueman, Holly E.; Mendoza, Jacqui; Bidwell, Shelby L.; Rajandream, Marie Adèle; Carucci, Daniel J.; Yates, John R.; Kafatos, Fotis C.; Janse, Chris J.; Barrell, Bart; Turner, C. Michael R.; Waters, Andrew P.; Sinden, Robert E.

doi:10.1126/science.1103717

Cited by 752 publications

(720 citation statements)

References 27 publications

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“…This finding agrees with most expression studies in Plasmodium spp., which consistently find abundant L3 transcripts and protein in liver (39,40) and iRBC stages (41). Although low abundance L3 transcripts were detected in sporozoites (42,43), L3 protein was undetectable (44) or nearly undetectable (42,43) by mass spectrometry compared with later timepoints. L3 is a reported discrete malaria CD8 + T-cell epitope carried on BALB/c malaria-infected erythrocytes; a few additional epitopes were reported in C57BL/6 mice (45).…”

Section: Hts Reveals Greater Ctl Diversity Following Different Sporozmentioning

confidence: 64%

A T-cell response to a liver-stagePlasmodiumantigen is not boosted by repeated sporozoite immunizations

Murphy

Kas²,

Stone³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Development of an antimalarial subunit vaccine inducing protective cytotoxic T lymphocyte (CTL)-mediated immunity could pave the way for malaria eradication. Experimental immunization with sporozoites induces this type of protective response, but the extremely large number of proteins expressed by Plasmodium parasites has so far prohibited the identification of sufficient discrete T-cell antigens to develop subunit vaccines that produce sterile immunity. Here, using mice singly immunized with Plasmodium yoelii sporozoites and high-throughput screening, we identified a unique CTL response against the parasite ribosomal L3 protein. Unlike CTL responses to the circumsporozoite protein (CSP), the population of L3-specific CTLs was not expanded by multiple sporozoite immunizations. CSP is abundant in the sporozoite itself, whereas L3 expression does not increase until the liver stage. The response induced by a single immunization with sporozoites reduces the parasite load in the liver so greatly during subsequent immunizations that L3-specific responses are only generated during the primary exposure. Functional L3-specific CTLs can, however, be expanded by heterologous prime-boost regimens. Thus, although repeat sporozoite immunization expands responses to preformed antigens like CSP that are present in the sporozoite itself, this immunization strategy may not expand CTLs targeting parasite proteins that are synthesized later. Heterologous strategies may be needed to increase CTL responses across the entire spectrum of Plasmodium liver-stage proteins.

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Section: Hts Reveals Greater Ctl Diversity Following Different Sporozmentioning

confidence: 64%

A T-cell response to a liver-stagePlasmodiumantigen is not boosted by repeated sporozoite immunizations

Murphy

Kas²,

Stone³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…While transcriptome and proteome analyses indicate that some genes are regulated post-transcriptionally [8,9], other genes are regulated at the level of transcription. For example, analyses of 5' end upstream regions of the asexual and sexual stages have been shown by transfection studies that they function as promoters by supporting reporter gene expression [10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

An enhancer-like region regulates hrp3 promoter stage-specific gene expression in the human malaria parasite Plasmodium falciparum

López-Estraño

Gopalakrishnan

Semblat

et al. 2007

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expres

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The asexual blood stage of Plasmodium falciparum is comprised of morphologically distinct ring, trophozoite and schizont stages. Each of these developmental stages possesses a distinct pattern of gene expression. Regulation of P. falciparum gene expression is thought to occur, at least in part, at the promoter level. Previously, we have found that although the RNA of the P. falciparum hrp3 gene is only seen in ring-stage parasites, deletion of a specific sequensce in the 5' end of the promoter region decreased ring-stage expression of hrp3 and enabled detection of its transcripts in trophozoitestage parasites. In order to investigate this stage specific regulation of gene expression, we employed a series of nested deletions of the 1.7-kb hrp3 promoter. Firefly luciferase gene was used as a reporter to evaluate the role of promoter sequences in gene regulation. Using this approach, we identified a ring-stage specific regulatory region on the hrp3 promoter located between -1.7-kb and -1.1-kb from the ATG initiation codon. Small 100-150 bp truncations on this enhancer-like region failed to uncover discrete regulatory sequences, suggesting the multipartite nature of this element. The data presented in this study demonstrates that stage specific promoter activity of the hrp3 gene in P. falciparum blood stage parasites is supported, at least in-part, by a small promoter region that can function in the absence of a larger chromosomal context.

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“…Second, almost 15% of annotated genes show transcription of antisense RNAs in the asexual stages [7]. Finally, results from genomewide transcription analyses and bioinformatics studies show that compared to the yeast genome, the Plasmodium genome has an under-representation of DNA-binding proteins and transcription factors and over-representation of RNA-binding proteins [8] Recent data that compares transcriptome and proteome profiles in different stages of the parasite life cycle has revealed that post-transcriptional regulation via RNA-binding proteins may be a major mechanism of regulating gene expression in gametocytes and sexual stages [9]. These accumulating data suggest that there may be novel mechanisms of gene regulation in the malaria parasite, including mRNA stabilization, antisense RNA and ncRNA-mediated regulation.…”

Section: Introductionmentioning

confidence: 99%

A screen for conserved sequences with biased base composition identifies noncoding RNAs in the A–T rich genome of Plasmodium falciparum

Upadhyay

Bawankar

Malhotra

et al. 2005

Molecular and Biochemical Parasitology

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A Comprehensive Survey of the Plasmodium Life Cycle by Genomic, Transcriptomic, and Proteomic Analyses

Cited by 752 publications

References 27 publications

A T-cell response to a liver-stagePlasmodiumantigen is not boosted by repeated sporozoite immunizations

A T-cell response to a liver-stagePlasmodiumantigen is not boosted by repeated sporozoite immunizations

An enhancer-like region regulates hrp3 promoter stage-specific gene expression in the human malaria parasite Plasmodium falciparum

A screen for conserved sequences with biased base composition identifies noncoding RNAs in the A–T rich genome of Plasmodium falciparum

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