Elucidation of malaria invasion mechanism into erythrocyte by reverse chemical genetics

• Project/Area Number: 26670202
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Ehime University
• Principal Investigator: Tsuboi Takafumi 愛媛大学, プロテオサイエンスセンター, 教授 (00188616)
• Co-Investigator(Kenkyū-buntansha): TAKASHIMA Eizo 愛媛大学, プロテオサイエンスセンター, 准教授 (50366762)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: マラリア / リバースケミカルジェネティクス / 赤血球侵入

Outline of Final Research Achievements

To develop a novel approach, reverse chemical genetics, for elucidation of malaria invasion mechanism into erythrocyte, we first identified a molecular-molecular interaction between malaria parasite proteins, GAMA and MSP10. We then successfully established a high-throughput screening system for inhibitors which will inhibit GAMA-MSP10 interaction by applying AlphaScreen technology. This screening system would be useful to discover not only novel malaria drug candidates but also elucidation of molecular mechanism of erythrocyte invasion of the parasite.

Research Products

• [Int'l Joint Research] Mahidol University(Thailand)
• [Int'l Joint Research] Kangwon National University(韓国)
• [Journal Article] Plasmodium vivax gametocyte proteins, Pvs48/45 and Pvs47, induce transmission-reducing antibodies by DNA immunization (2015)
  • Author(s): Tachibana M, Suwanabun N, Kaneko O, Iriko H, Otsuki H, Sattabongkot J, Kaneko A, Herrera S, Torii M, Tsuboi T
  • Journal Title: Vaccine Volume: 33 Issue: 16 Pages: 1901-1908
  • DOI: 10.1016/j.vaccine.2015.03.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Rodent malaria lactate dehydrogenase assay provides a high throughput solution for in vivo vaccine studies (2015)
  • Author(s): Otsuki H, Yokouchi Y, Iyoku N, Tachibana M, Tsuboi T, Torii M
  • Journal Title: Parasitol Int Volume: 64 Issue: 4 Pages: 60-63
  • DOI: 10.1016/j.parint.2015.02.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Immunoprofiling of the tryptophan-rich antigen family in Plasmodium vivax (2015)
  • Author(s): Wang B, Lu F, Cheng Y, Chen JH, Jeon HY, Ha KS, Cao J, Nyunt MH, Han JH, Lee SK, Kyaw MP, Sattabongkot J, Takashima E, Tsuboi T, Han ET
  • Journal Title: Infect Immun Volume: 83 Issue: 8 Pages: 3083-3095
  • DOI: 10.1128/iai.03067-14
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Application of wheat germ cell-free protein expression system for novel malaria vaccine candidate discovery (2014)
  • Author(s): Arumugam TU, Ito D, Takashima E, Tachibana M, Ishino T, Torii M, Tsuboi T
  • Journal Title: Expert Review of Vaccines Volume: 13 Issue: 1 Pages: 75-85
  • DOI: 10.1586/14760584.2014.861747
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tricomponent complex loaded with a mosquito-stage antigen of the malaria parasite induces potent transmission-blocking immunity (2014)
  • Author(s): Arakawa T, Tsuboi T, Sattabongkot J, Sakao K, Torii M, Miyata T
  • Journal Title: Clinical and Vaccine Immunology Volume: 21 Issue: 4 Pages: 561-569
  • DOI: 10.1128/cvi.00053-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Profiling the humoral immune responses to Plasmodium vivax infection and identification of candidate immunogenic rhoptry-associated membrane antigen (RAMA) (2014)
  • Author(s): Lu F, Li J, Wang B, Cheng Y, Kong DH, Cui L, Ha KS, Sattabongkot J, Tsuboi T, Han ET
  • Journal Title: Journal of Proteomics Volume: 102 Pages: 66-82
  • DOI: 10.1016/j.jprot.2014.02.029
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Immunogenicity and antigenicity of Plasmodium vivax merozoite surface protein 10 (2014)
  • Author(s): Cheng Y, Wang B, Sattabongkot J, Lim CS, Tsuboi T, Han ET
  • Journal Title: Parasitology Research Volume: 113 Issue: 7 Pages: 2559-2568
  • DOI: 10.1007/s00436-014-3907-8
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] ポストゲノムマラリアワクチン研究は宿主寄生体関係の総体的理解につながる (2015)
  • Author(s): 坪井敬文
  • Organizer: 第88回日本生化学会大会・第38回日本分子生物学会年会 合同大会
  • Place of Presentation: 神戸ポートアイランド、神戸市、兵庫県
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] Pre-erythrocytic vaccines for malaria elimination (2015)
  • Author(s): Tsuboi T
  • Organizer: Malaria R&D in a Time of Global Partnerships
  • Place of Presentation: 東京大学、東京都
  • Year and Date: 2015-06-26
  • Int'l Joint Research / Invited
• [Presentation] An integrated approach to tackling malaria in Uganda with special reference to novel malaria vaccine candidate discovery (2015)
  • Author(s): Tsuboi T, Kanoi BN, Egwang TG, Horii T
  • Organizer: E-JUST 2nd International Conference on Innovative Engineering
  • Place of Presentation: Bibliotheca Alexandria, Alexandria, Egypt
  • Year and Date: 2015-05-19
  • Int'l Joint Research / Invited
• [Presentation] WGCFS: an innovative technology for post-genome malaria vaccine research (2015)
  • Author(s): Tsuboi T
  • Organizer: 25th Annual Molecular Parasitology/Vector Biology Symposium
  • Place of Presentation: University of Georgia, Athens, USA
  • Year and Date: 2015-04-28
  • Int'l Joint Research / Invited
• [Presentation] Wheat germ cell-free protein synthesis system (WGCFS): a breakthrough for the post-genome malaria research (2014)
  • Author(s): Tsuboi T
  • Organizer: Seminar at the Department of Parasite and Insect Vectors, Institut Pasteur
  • Place of Presentation: Paris, France
  • Year and Date: 2014-12-18
  • Invited
• [Presentation] Wheat germ cell-free protein synthesis system: an innovative technology for post-genome malaria vaccine candidate discovery (2014)
  • Author(s): Tsuboi T
  • Organizer: Seminar at the Laboratory of Malaria and Vector Research, NIAID, NIH
  • Place of Presentation: Rockville, USA
  • Year and Date: 2014-11-07
  • Invited
• [Presentation] Global Health Innovation through Partnership (2014)
  • Author(s): Tsuboi T
  • Organizer: 第55回日本熱帯医学会大会・第29回日本国際保健医療学会学術大会合同大会
  • Place of Presentation: 東京女子医科大学、東京都
  • Year and Date: 2014-11-01 – 2014-11-03
  • Invited
• [Presentation] Characterization of Plasmodium falciparum MAS170 as novel malaria blood-stage vaccine candidate (2014)
  • Author(s): Sasaoka C, Sakamoto H, Ito D, Takeo S, Sattabongkot J, Takashima E, Tsuboi T
  • Organizer: The 13th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 奈良春日野国際フォーラム、奈良市、奈良県
  • Year and Date: 2014-09-23 – 2014-09-26
• [Presentation] Wheat germ cell-free protein synthesis system: an innovative technology for post-genome malaria vaccine candidate discovery (2014)
  • Author(s): 坪井敬文
  • Organizer: 第157回日本獣医学会学術集会、日本獣医寄生虫学会国際シンポジウム
  • Place of Presentation: 北海道大学、札幌市、北海道
  • Year and Date: 2014-09-09 – 2014-09-12
  • Invited
• [Presentation] Wheat germ cell-free protein synthesis system (WGCFS): a breakthrough for the post-genome vivax malaria research (2014)
  • Author(s): Tsuboi T, Takashima E, Ito D, Feng Lu, Cheng Y, Han ET
  • Organizer: 13th International Congress of Parasitology
  • Place of Presentation: Mexico City, Mexico
  • Year and Date: 2014-08-10 – 2014-08-15
  • Invited
• [Remarks] 愛媛大学プロテオサイエンスセンター マラリア研究部門
  • URL: http://www.pros.ehime-u.ac.jp/malaria/