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Random mutagenesis of P. flaciparum by ENU

Research Project

Project/Area Number 26670199
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Parasitology (including sanitary zoology)
Research InstitutionMie University

Principal Investigator

IWANAGA SHIROH  三重大学, 医学(系)研究科(研究院), 准教授 (20314510)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsマラリア / ENU / 感染症
Outline of Final Research Achievements

N-ethyl-N-nitrosourea (ENU) is a potent mutagen and is widely used for random mutagenesis. In the present study, we utilized it for generating the parasite population, whose genomic sequence were randomly mutated, and selected the mefloquine-resistant parasites from them. The obtained mefloquine-resistant parasites exhibited 3 folds stronger resistance than the wild-type parasite. Genomic sequence analysis showed that approximately 2,000 mutations were introduced by ENU treatment. To identify the drug resistant gene, genomic DNA library of mefloquine-resistant parasite was directly generated in drug sensitive parasites using P. falciparum centromere plasmid and the generated library was treated with mefloquine. After three rounds of treatments, three independent parasite clones, which acquired newly mefloquine resistance, were obtained. The centromere plasmids are being recovered from those selected parasites and the drug resistant gene is being identified now.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (2 results)

All 2015

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results)

  • [Journal Article] Global transcriptional repression: An initial and essential step for Plasmodium sexual development2015

    • Author(s)
      Yuda M, Iwanaga S, Kaneko I, Kato T.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 112 Issue: 41 Pages: 12824-12829

    • DOI

      10.1073/pnas.1504389112

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-Wide Identification of the Target Genes of AP2-O, a Plasmodium AP2-Family Transcription Factor2015

    • Author(s)
      Yuda M, Iwanaga S, Kaneko I, Kato T
    • Journal Title

      PLoS Pathog

      Volume: 11 Issue: 5 Pages: 1-27

    • DOI

      10.1371/journal.ppat.1004905

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access

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Published: 2014-04-04   Modified: 2018-01-16  

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