2002 Fiscal Year Annual Research Report

遺伝子導入によるマラリアを伝播しないハマダラカの作製

Research Project

Project/Area Number	13670253
Research Institution	Jichi Medical School
Principal Investigator	吉田栄人自治医科大学, 医学部, 講師 (10296121)
Co-Investigator(Kenkyū-buntansha)	平井誠自治医科大学, 医学部, 助手 (50326849) 松岡裕之自治医科大学, 医学部, 助教授 (10173816)
Keywords	マラリア / ハマダラカ / 遺伝子導入 / トランスジェニック / 一本鎖抗体
Research Abstract	研究代表者(吉田)は海外共同研究者であるProf.Crisantiのグループと共同でハマダラカのカルボキシペプチターゼ遺伝子プロモーター領域をクローニングし、抗マラリア活性を有する一本鎖抗体遺伝子をこのプロモーター下に連結したプラスミドベクターを構築した。ハマダラカ卵にこのベクターDNAをインジェクションして4系統のトランスジェニック蚊を確立した。このトランスジェニック蚊は、吸血3時間後にはカルボキシペプチターゼ遣伝子プロモーターが活性化し、中腸内で一本鎖抗体遺伝子の発現を強力に誘導することを明らかにした。しかしながらこれらのトランスジェニックハマダラカにはマラリア伝播阻止能はなかった。現在中腸分泌型コンストラクトを持ったトランスジェニック蚊を作製中である。Prof.Crisantiのグループはハチ毒タンパクを発現するトランスジェニックハマダラカを作製し、これにマラリア伝播阻止能があることを見出した(JBC2002)。またトランスジェニックハマダラカによるマラリアコントロールの方向性を示す報告として、トランスジェニックハマダラカはWTに淘汰されないような工夫を施すことが必須であることを明確にした(Science2003)。海外共同研究者であるProf.Sindenのグループは熱帯熱マラリア原虫の各ステージにおけるタンパク発現プロファイルを明らかにした(Nature 2002)。またマウスマラリアゲノムプロジェクトにも参加し、その全塩基配列を明らかにした(Nature 2002)。

Research Products

(20 results)

All Other

All Publications (20 results)

[Publications] Yoshida S: "T-cell activation and cytokine production via a bispecific single-chain antibody fragment targeted to blood-stage malaria parasites"Blood. 101. 2300-2306 (2003)
[Publications] Matsuoka H: "A rodent malaria, Plasmodium berghei, is experimentally transmitted to mice by merely probing of infective mosquito, Anopheles stephensi"Parasitol Int. 51. 17-23 (2002)
[Publications] Catteruccia F: "Impact of genetic manipulation on the fitness of Anopheles stephensi mosquitoes"Science. 299. 1225-1227 (2003)
[Publications] Alphey L: "Malaria control with genetically manipulated insect vectors"Science. 298. 119-121 (2002)
[Publications] Tewari R: "Function of region I and II adhesive motifs of Plasmodium falciparum circumsporozoite protein in sporozoite motility and infectivity"J Biol Chem. 277. 47613-47618 (2002)
[Publications] Moreira LA: "Bee venom phospholipase inhibits malaria parasite development in transgenic mosquitoes"J Biol Chem. 277. 40839-40843 (2002)
[Publications] Carlton JM: "Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii"Nature. 419. 512-519 (2002)
[Publications] Claudianos C: "A malaria scavenger receptor-like protein essential for parasite development"Mol Microbiol. 45. 1473-1484 (2002)
[Publications] Rodriguez MC: "Plasmodium berghei : routine production of pure gametocytes, extracellular gametes, zygotes, and ookinetes"Exp Parasitol. 101. 73-76 (2002)
[Publications] Sinden RE: "Maintenance of the Plasmodium berghei life cycle"Methods Mol Med. 72. 25-40 (2002)
[Publications] Dimopoulos G: "Malaria parasites and the anopheles mosquito"Chem Immunol. 80. 27-49 (2002)
[Publications] Al-Olayan EM: "Complete development of mosquito phases of the malaria parasite in vitro"Science. 295. 677-679 (2002)
[Publications] Opitz C: "Intramembrane cleavage of microneme proteins at the surface of the apicomplexan parasite Toxoplasma gondii"EMBO J. 21. 1577-1585 (2002)
[Publications] Vlachou D: "piggyBac-mediated germline transformation of the malaria mosquito Anopheles stephensi using the red fluorescent protein dsRED as a selectable marker"J Biol Chem. 277. 8759-8762 (2002)
[Publications] Butcher GA: "Persistence of atovaquone in human sera following treatment : inhibition of Plasmodium falciparum development in vivo and in vitro"Am J Trop Med Hyg. 68. 111-114 (2003)
[Publications] Billker O: "Azadirachtin disrupts formation of organised microtubule arrays during microgametogenesis of Plasmodium berghei"J Eukaryot Microbiol. 49. 489-497 (2002)
[Publications] Sinden RE: "Molecular interactions between Plasmodium and its insect vectors"Cell Microbiol. 4. 713-724 (2002)
[Publications] Florens L: "A proteomic view of the Plasmodium falciparum life cycle"Nature. 419. 520-526 (2002)
[Publications] Claudianos C: "A malaria scavenger receptor-like protein essential for parasite development"Mol Microbiol. 45. 1473-1484 (2002)
[Publications] Gilbert SC: "Enhanced CD8 T cell immunogenicity and protective efficacy in a mouse malaria model using a recombinant adenoviral vaccine in heterologous primeboost immunisation regimes"Vaccine. 20. 1039-1045 (2002)

2002 Fiscal Year Annual Research Report

遺伝子導入によるマラリアを伝播しないハマダラカの作製

Principal Investigator

吉田 栄人 自治医科大学, 医学部, 講師 (10296121)

Research Products

[Publications] Yoshida S: "T-cell activation and cytokine production via a bispecific single-chain antibody fragment targeted to blood-stage malaria parasites"Blood. 101. 2300-2306 (2003)

[Publications] Matsuoka H: "A rodent malaria, Plasmodium berghei, is experimentally transmitted to mice by merely probing of infective mosquito, Anopheles stephensi"Parasitol Int. 51. 17-23 (2002)

[Publications] Catteruccia F: "Impact of genetic manipulation on the fitness of Anopheles stephensi mosquitoes"Science. 299. 1225-1227 (2003)

[Publications] Alphey L: "Malaria control with genetically manipulated insect vectors"Science. 298. 119-121 (2002)

[Publications] Tewari R: "Function of region I and II adhesive motifs of Plasmodium falciparum circumsporozoite protein in sporozoite motility and infectivity"J Biol Chem. 277. 47613-47618 (2002)

[Publications] Moreira LA: "Bee venom phospholipase inhibits malaria parasite development in transgenic mosquitoes"J Biol Chem. 277. 40839-40843 (2002)

[Publications] Carlton JM: "Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii"Nature. 419. 512-519 (2002)

[Publications] Claudianos C: "A malaria scavenger receptor-like protein essential for parasite development"Mol Microbiol. 45. 1473-1484 (2002)

[Publications] Rodriguez MC: "Plasmodium berghei : routine production of pure gametocytes, extracellular gametes, zygotes, and ookinetes"Exp Parasitol. 101. 73-76 (2002)

[Publications] Sinden RE: "Maintenance of the Plasmodium berghei life cycle"Methods Mol Med. 72. 25-40 (2002)

[Publications] Dimopoulos G: "Malaria parasites and the anopheles mosquito"Chem Immunol. 80. 27-49 (2002)

[Publications] Al-Olayan EM: "Complete development of mosquito phases of the malaria parasite in vitro"Science. 295. 677-679 (2002)

[Publications] Opitz C: "Intramembrane cleavage of microneme proteins at the surface of the apicomplexan parasite Toxoplasma gondii"EMBO J. 21. 1577-1585 (2002)

[Publications] Vlachou D: "piggyBac-mediated germline transformation of the malaria mosquito Anopheles stephensi using the red fluorescent protein dsRED as a selectable marker"J Biol Chem. 277. 8759-8762 (2002)

[Publications] Butcher GA: "Persistence of atovaquone in human sera following treatment : inhibition of Plasmodium falciparum development in vivo and in vitro"Am J Trop Med Hyg. 68. 111-114 (2003)

[Publications] Billker O: "Azadirachtin disrupts formation of organised microtubule arrays during microgametogenesis of Plasmodium berghei"J Eukaryot Microbiol. 49. 489-497 (2002)

[Publications] Sinden RE: "Molecular interactions between Plasmodium and its insect vectors"Cell Microbiol. 4. 713-724 (2002)

[Publications] Florens L: "A proteomic view of the Plasmodium falciparum life cycle"Nature. 419. 520-526 (2002)

[Publications] Claudianos C: "A malaria scavenger receptor-like protein essential for parasite development"Mol Microbiol. 45. 1473-1484 (2002)

[Publications] Gilbert SC: "Enhanced CD8 T cell immunogenicity and protective efficacy in a mouse malaria model using a recombinant adenoviral vaccine in heterologous primeboost immunisation regimes"Vaccine. 20. 1039-1045 (2002)

吉田栄人自治医科大学, 医学部, 講師 (10296121)