Unified Understanding of the Plasmodium Life Cycle by Targetome Analysis

• Project/Area Number: 17H01542
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Mie University
• Principal Investigator: yuda masao 三重大学, 医学系研究科, 教授 (90293779)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥40,820,000 (Direct Cost: ¥31,400,000、Indirect Cost: ¥9,420,000); Fiscal Year 2019: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2018: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2017: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
• Keywords: マラリア / 転写因子 / ターゲトーム / マラリア原虫 / 感染症 / ゲノム

Outline of Final Research Achievements

In this study, we analyzed the function of each Plasmodium transcription factor, identified its binding sequences, and determined target genes. Our results demonstrated the unique transcriptional regulation mechanism of Plasmodium parasites, in which a stage-specific transcription factor directly and comprehensively regulates genes and determines the gene expression repertoire at each stage. We have also revealed the dynamic linkage of gene expression through the lifecycle by viewing it as a chain of targetomes.

Academic Significance and Societal Importance of the Research Achievements

転写制御は遺伝子発現制御の中核をなし、その機構を解明することはポストゲノム研究の中心的課題である。マラリア原虫は、１つの転写因子が各ステージを直接制御し遺伝子発現レパートリーを決定するというユニークな転写制御機構を有している。本研究はこの転写制御機構に着目し、ターゲトームから “ステージ形成のマスタープラン”を読み解くことを試みたものである。本研究で得られたターゲトーム情報は感染・寄生の分子機構解明などマラリア原虫のポストゲノム研究を強力にサポートするものである

Research Products

• [Journal Article] Chromosome splitting of Plasmodium berghei using the CRISPR/Cas9 system (2022)
  • Author(s): Addo-Gyan Daniel、Matsushita Haruka、Sora Enya、Nishi Tsubasa、Yuda Masao、Shinzawa Naoaki、Iwanaga Shiroh
  • Journal Title: PLOS ONE Volume: 17 Issue: 2 Pages: 0260176-0260176
  • DOI: 10.1371/journal.pone.0260176
  • Peer Reviewed / Open Access
• [Journal Article] Mechanisms of triggering malaria gametocytogenesis by AP2-G (2021)
  • Author(s): Yuda Masao、Kaneko Izumi、Murata Yuho、Iwanaga Shiroh、Nishi Tsubasa
  • Journal Title: Parasitology International Volume: 84 Pages: 102403-102403
  • DOI: 10.1016/j.parint.2021.102403
  • Peer Reviewed
• [Journal Article] Highly efficient CRISPR/Cas9 system in Plasmodium falciparum using Cas9-expressing parasites and a linear donor template (2021)
  • Author(s): Nishi Tsubasa、Shinzawa Naoaki、Yuda Masao、Iwanaga Shiroh
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 18501-18502
  • DOI: 10.1038/s41598-021-97984-z
  • Peer Reviewed / Open Access
• [Journal Article] Improvement of CRISPR/Cas9 system by transfecting Cas9-expressing Plasmodium berghei with linear donor template (2020)
  • Author(s): Shinzawa Naoaki、Nishi Tsubasa、Hiyoshi Fumiya、Motooka Daisuke、Yuda Masao、Iwanaga Shiroh
  • Journal Title: Communications Biology Volume: 3 Issue: 1 Pages: 1-1
  • DOI: 10.1038/s42003-020-01138-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Female‐specific gene regulation in malaria parasites by an AP2‐family transcription factor (2019)
  • Author(s): Yuda Masao、Kaneko Izumi、Iwanaga Shiroh、Murata Yuho、Kato Tomomi
  • Journal Title: Molecular Microbiology Volume: 113 Issue: 1 Pages: 40-51
  • DOI: 10.1111/mmi.14334
  • Peer Reviewed / Open Access
• [Journal Article] CXCR4 regulates Plasmodium development in mouse and human hepatocytes (2019)
  • Author(s): Bando Hironori、Pradipta Ariel、Iwanaga Shiroh、Okamoto Toru、Okuzaki Daisuke、Tanaka Shun、Vega-Rodr?guez Joel、Lee Youngae、Ma Ji Su、Sakaguchi Naoya、Soga Akira、Fukumoto Shinya、Sasai Miwa、Matsuura Yoshiharu、Yuda Masao、Jacobs-Lorena Marcelo、Yamamoto Masahiro
  • Journal Title: Journal of Experimental Medicine Volume: 216 Issue: 8 Pages: 1733-1748
  • DOI: 10.1084/jem.20182227
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cytotoxic anti-circumsporozoite antibodies target malaria sporozoites in the host skin (2018)
  • Author(s): Aliprandini Eduardo、Tavares Joana、Panatieri Raquel Hoffmann、Thiberge Sabine、Yamamoto Marcio Massao、Silvie Olivier、Ishino Tomoko、Yuda Masao、Dartevelle Sylvie、Traincard Francois、Boscardin Silvia Beatriz、Amino Rogerio
  • Journal Title: Nature Microbiology Volume: 3 Issue: 11 Pages: 1224-1233
  • DOI: 10.1038/s41564-018-0254-z
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] CRISPR/Cas9 system in Plasmodium falciparum using the centromere plasmid (2018)
  • Author(s): Payungwoung Tongchai、Shinzawa Naoaki、Hino Akina、Nishi Tubasa、Murata Yuho、Yuda Masao、Iwanaga Shiroh
  • Journal Title: Parasitology International Volume: 67 Issue: 5 Pages: 605-608
  • DOI: 10.1016/j.parint.2018.06.002
  • Peer Reviewed / Open Access
• [Journal Article] Nonspecific CD8+ T Cells and Dendritic Cells/Macrophages Participate in Formation of CD8+ T Cell-Mediated Clusters against Malaria Liver-Stage Infection (2018)
  • Author(s): Akbari Masoud、Kimura Kazumi、Bayarsaikhan Ganchimeg、Kimura Daisuke、Miyakoda Mana、Juriasingani Smriti、Yuda Masao、Amino Rogerio、Yui Katsuyuki
  • Journal Title: Infection and Immunity Volume: 86 Issue: 4
  • DOI: 10.1128/iai.00717-17
  • NAID: 120006988034
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A potent malaria vaccine based on adenovirus with dual modifications at Hexon and pVII (2017)
  • Author(s): Shiratsuchi Takayuki、Rai Urvashi、Kaneko Izumi、Zhang Min、Iwanaga Shiroh、Yuda Masao、Tsuji Moriya
  • Journal Title: Vaccine Volume: 35 Issue: 50 Pages: 6990-7000
  • DOI: 10.1016/j.vaccine.2017.10.066
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Activation and exhaustion of antigen-specific CD8+ T cells occur in different splenic compartments during infection with Plasmodium berghei. (2017)
  • Author(s): 1.Bayarsaikhan G, Miyakoda M, Yamamoto K, Kimura D, Akbari M, Yuda M, Yui K
  • Journal Title: Parasitol Int Volume: 66(3) Issue: 3 Pages: 227-235
  • DOI: 10.1016/j.parint.2017.01.022
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Cas9 ヌクレアーゼ発現熱帯熱マラリア原虫を用いた新規ゲノム編集法の確立 (2019)
  • Author(s): 西翔, 新澤直明, 平山泰士, 油田正夫, 岩永史朗
  • Organizer: 日本寄生虫学会
• [Presentation] マラリア原虫のAP2-FGは雌生殖母体形成のマスター転写因子である (2018)
  • Author(s): 村田 優穂, 金子 伊澄, 加藤 知美, 岩永 史郎, 油田正夫
  • Organizer: 第87会日本寄生虫学会大会