| Project/Area Number |
06044183
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Nagasaki University |
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Principal Investigator |
UEMURA Haruki Nagasaki University, Institute of Tropical Medicine, Assistant Professor, 熱帯医学研究所, 講師 (60184975)
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| Co-Investigator(Kenkyū-buntansha) |
EICHINGER Daniel New York University, Medical Center, Assistant Professor, 医学部, 助教授
SCHENKMAN Sergio Escola Paulista de Medicina, Professor, 教授
KANBARA Hiroji Nagasaki University, Institute o Tropical Medicine, Professor, 熱帯医学研究所, 教授 (20029789)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1995: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | Trypanosoma / Trans-sialidase / Sialic acid / Cell invasion / Trypomastigote / Chagas' disese / Multiple copy gene / Trypanosoma / Trans-sialidase / アフリカ睡眠病 / Trypomastigote / Epimastigote |
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| Research Abstract |
Trans-sialidase (TS) is a unique enzyme found in protozoan Trypanosoma. This enzyme catalyzes sialic acid transfer reaction from host derived glycoconjugates to parasite surface acceptor molecules. This enzyme is first found in trypomasitigote stage of Trypanosoma cruzi, causative agent of Chagas' disease The sialic acids, transferred to the parasite surface glycoprotein are suggested to be important for cell invasion and escape from host defense systems.
Sequence analysis of T.cruzi TS genes have shown that trans-sialidase is encoded by several gene family and only some members of this family encode enzymatically active proteins. The active and inactive forms of the genes contain. different numbers of carboxy terminal twelve amino acid repeat units and also some substitutions in the amino terminal catalytic domains. We reported that difference in activity is not due to carboxy-terminal region, but due to single amino acid differences at the animo-terminal domain.
To examine the ratio of active and inactive protein genes, we amplified the region where is important for enzyme activity and contains most of amino acid substitutions. We obtained the result taht half of the genes are active and the other half inactive types. In addition, sequencing of these amplifid clones revealed there are several additional types of substitutions in this region.
Then, we analyzed TS gene organization and obtained the result that different types of genes are distributed in more than one chromosomal band. In the Y-strain, all repeat-containing genes are localized in one chromosomal band of 1.1 megabases, while the repeat-minus genes are in two other chromosome s of 0.82 and 0.79 megabases.
Eichinger's group has obtained the sialidase gene from T.rangeli. A comparative analysis of T.cruzi TS and T.rangeli sialidase is helpful to determine the feature of TS protein which contribute to its unique sialic acid transfer reaction.
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