| Project/Area Number |
14570228
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
寄生虫学(含医用動物学)
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| Research Institution | KURUME UNIVERSITY |
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Principal Investigator |
FUKUMA Toshihide Kurume Univ.Sch.Med., Dept.Parasitol., Professor, 医学部, 教授 (90125146)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Masahiro Univ.Sch.Med., Dept.Parasitol., Associate Professor, 医学部, 講師 (00232562)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | 14-3-3 / Trypanosoma b.brucei / dsRNAi / pQuadra / African trypanosomiasis / therapeutic target / therapeuticc target / Trypanosoma brucei |
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| Research Abstract |
Protein 14-3-3 was described to be rich in CNS and ubiquitously found in eukaryotic organisms of plants and animals. Quite a many proteins have been reported to bind to 14-3-3 then it is estimated the protein has important roles in the cell cycle, apoptosis and other signal transduction paths.
We examined 14-3-3 of Trypanosoma b.brucei (Tb) and remark the followings.
1) The genes of 2 isotypes (I, II) of 14-3-3 could be cloned. The result produced the recombinant proteins and sensitive mono-specific rat antibodies against them.
2) Though 14-3-3 distinctive motifs are conserved, the characteristics of trypanosome 14-3-3 are quite different form those of mammals.
3) We developed solely effective vector construct named pQuadra (pQ) to perform dsRNAi without leakage before induction.
4) Procyclic forms (pr) were examined by dsRNAi on 14-3-3 applying pQ. Morphologically pr was damaged to bizarre multiflagellated form and disoriented kinetoplsts or nuclei delivery. The growth of pr was suppressed.
5)On blood stream forms (bs) after induction of dsRNAi with pQ more drastic effect appeared earlier than pr and the growth was entirely suppressed
6) The morphological change of bs was very similar to the effect of okadaic acid addition to culture of bs, which is protein phosphates (pp) inhibitor. Analysis based on relation between 14-3-3 and pp we came very close to the therapeutic target of African trypanosomiasis.
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