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A proteomic view of the Plasmodium falciparum life cycle

Nature volume 419, pages 520–526 (2002) Cite this article

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Abstract

The completion of the Plasmodium falciparum clone 3D7 genome provides a basis on which to conduct comparative proteomics studies of this human pathogen. Here, we applied a high-throughput proteomics approach to identify new potential drug and vaccine targets and to better understand the biology of this complex protozoan parasite. We characterized four stages of the parasite life cycle (sporozoites, merozoites, trophozoites and gametocytes) by multidimensional protein identification technology. Functional profiling of over 2,400 proteins agreed with the physiology of each stage. Unexpectedly, the antigenically variant proteins of var and rif genes, defined as molecules on the surface of infected erythrocytes, were also largely expressed in sporozoites. The detection of chromosomal clusters encoding co-expressed proteins suggested a potential mechanism for controlling gene expression.

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Figure 1: Functional profiles of expressed proteins.
Figure 2: Expression patterns of known stage-specific proteins.
Figure 3: Distribution of expressed proteins by chromosome.

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Acknowledgements

We are grateful to J. Graumann, R. Sadygov, G. Chukkapalli, A. Majumdar and R. Sinkovits for computer programming; C. Deciu for the probability calculations; and C. Delahunty and C. Vieille for critical reading of the manuscript. The authors acknowledge the support of the Office of Naval Research, the US Army Medical Research and Material Command, and the National Institutes of Health (to J.R.Y.). J.D.R. is funded by a Wellcome Trust Prize Studentship. We thank the scientists and funding agencies comprising the international Malaria Genome Project for making sequence data from the genome of P. falciparum clone 3D7 public before publication of the completed sequence. The opinions expressed are those of the authors and do not reflect the official policy of the Department of the Navy, Department of Defense, or the US government.

Author information

Author notes

  1. John B. Sacci

    Present address: BRB 13-009, Department of Microbiology and Immunology, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, Maryland, 21201, USA

  2. Adam A. Witney

    Present address: Department of Medical Microbiology, St George's Hospital Medical School, Cranmer Terrace, London, SW17 0RE, UK

  3. Dirk Wolters

    Present address: Ruhr-University Bochum, Institute of Analytical Chemistry, 44780, Bochum, Germany

Authors and Affiliations

  1. Department of Cell Biology, The Scripps Research Institute, SR-11, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA

    Laurence Florens, Nemone Muster, David L. Tabb & John R. Yates

  2. Department of Proteomics and Metabolomics, Torrey Mesa Research Institute, Syngenta Research & Technology, 3115 Merryfield Row, San Diego, California, 92121-1125, USA

    Michael P. Washburn, Dirk Wolters & John R. Yates

  3. Infection and Immunity Section, Department of Biological Sciences, Imperial College of Science, Technology & Medicine, Sir Alexander Fleming Building, SW7 2AZ, South Kensington, London, UK

    J. Dale Raine & Robert E. Sinden

  4. Naval Medical Research Center, Malaria Program (IDD), 503 Robert Grant Avenue, Room 3A40, Silver Spring, Maryland, 20910-7500, USA

    Robert M. Anthony, J. David Haynes, J. Kathleen Moch, John B. Sacci, Adam A. Witney & Daniel J. Carucci

  5. Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland, 20910-7500, USA

    J. David Haynes

  6. The Division of Parasitology, National Institute for Medical Research, The Ridgeway, NW7 1AA, Mill Hill, London, UK

    Munira Grainger & Anthony A. Holder

  7. Department of Genome Sciences, University of Washington, Seattle, Washington, 98195, USA

    David L. Tabb

  8. Malaria Research and Reference Reagent Resource Center, American Type Culture Collection, 10801 University Boulevard, Manassas, Virginia, 20110-2209, USA

    Yimin Wu

  9. The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, Maryland, 20850, USA

    Michael P. Washburn, Dirk Wolters, Malcolm J. Gardner & John R. Yates

Authors
  1. Laurence Florens
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Correspondence to John R. Yates.

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Florens, L., Washburn, M., Raine, J. et al. A proteomic view of the Plasmodium falciparum life cycle. Nature 419, 520–526 (2002). https://doi.org/10.1038/nature01107

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