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CRISPR/Cas9-engineered inducible gametocyte producer lines as a valuable tool for Plasmodium falciparum malaria transmission research

Author

Listed:
  • Sylwia D. Boltryk

    (Swiss Tropical and Public Health Institute
    University of Basel)

  • Armin Passecker

    (Swiss Tropical and Public Health Institute
    University of Basel)

  • Arne Alder

    (Centre for Structural Systems Biology
    Bernhard Nocht Institute for Tropical Medicine
    University of Hamburg)

  • Eilidh Carrington

    (Swiss Tropical and Public Health Institute
    University of Basel)

  • Marga Vegte-Bolmer

    (Radboud University Medical Center)

  • Geert-Jan Gemert

    (Radboud University Medical Center)

  • Alex Starre

    (Radboud University Medical Center)

  • Hans-Peter Beck

    (Swiss Tropical and Public Health Institute
    University of Basel)

  • Robert W. Sauerwein

    (Radboud University Medical Center)

  • Taco W. A. Kooij

    (Radboud University Medical Center)

  • Nicolas M. B. Brancucci

    (Swiss Tropical and Public Health Institute
    University of Basel)

  • Nicholas I. Proellochs

    (Radboud University Medical Center)

  • Tim-Wolf Gilberger

    (Centre for Structural Systems Biology
    Bernhard Nocht Institute for Tropical Medicine
    University of Hamburg)

  • Till S. Voss

    (Swiss Tropical and Public Health Institute
    University of Basel)

Abstract

The malaria parasite Plasmodium falciparum replicates inside erythrocytes in the blood of infected humans. During each replication cycle, a small proportion of parasites commits to sexual development and differentiates into gametocytes, which are essential for parasite transmission via the mosquito vector. Detailed molecular investigation of gametocyte biology and transmission has been hampered by difficulties in generating large numbers of these highly specialised cells. Here, we engineer P. falciparum NF54 inducible gametocyte producer (iGP) lines for the routine mass production of synchronous gametocytes via conditional overexpression of the sexual commitment factor GDV1. NF54/iGP lines consistently achieve sexual commitment rates of 75% and produce viable gametocytes that are transmissible by mosquitoes. We also demonstrate that further genetic engineering of NF54/iGP parasites is a valuable tool for the targeted exploration of gametocyte biology. In summary, we believe the iGP approach developed here will greatly expedite basic and applied malaria transmission stage research.

Suggested Citation

  • Sylwia D. Boltryk & Armin Passecker & Arne Alder & Eilidh Carrington & Marga Vegte-Bolmer & Geert-Jan Gemert & Alex Starre & Hans-Peter Beck & Robert W. Sauerwein & Taco W. A. Kooij & Nicolas M. B. Br, 2021. "CRISPR/Cas9-engineered inducible gametocyte producer lines as a valuable tool for Plasmodium falciparum malaria transmission research," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24954-4
    DOI: 10.1038/s41467-021-24954-4
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    Cited by:

    1. Josie L. Ferreira & Vojtěch Pražák & Daven Vasishtan & Marc Siggel & Franziska Hentzschel & Annika M. Binder & Emma Pietsch & Jan Kosinski & Friedrich Frischknecht & Tim W. Gilberger & Kay Grünewald, 2023. "Variable microtubule architecture in the malaria parasite," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Jiahong Li & Gerald J. Shami & Ellie Cho & Boyin Liu & Eric Hanssen & Matthew W. A. Dixon & Leann Tilley, 2022. "Repurposing the mitotic machinery to drive cellular elongation and chromatin reorganisation in Plasmodium falciparum gametocytes," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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