| Project/Area Number |
07670284
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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 | Nagasaki University |
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Principal Investigator |
UEMURA Haruki Institute of Tropical Medicine, Assistant Professor, 熱帯医学研究所, 講師 (60184975)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAZAWA Shusuke Institute of Tropical Medicine, Research Associate, 熱帯医学研究所, 助手 (20180268)
KANBARA Hiroji Institute of Tropical Medicine, Professor, 熱帯医学研究所, 教授 (20029789)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Chagas' disease / Trans-sialidase / sialic acid / Trypanosoma / Trypomastigote / Gene expression / GPI-anchored protein / 遺伝子多様性 |
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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 trypomastigote 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.
We have analyzed the gene structure of T.cruzi trans-sialidase. Trans-sialidase is highly expressed in trypomastigote stage and the genes for these proteins are arranged in clusters of tandem array. The other type of trans-sialidase is detectable at the insect stage of parasite, epimastigote. These two types of trans-sialidase genes are localized at the different chromosomes and may be regulated independently. Catalytic domain of these two trans-sialidase molecule shear more than 80% of similarities, however these amino- and carboxyl- terminal regions have no similarities. Most remarkable differences in these enzymes are at their C-terminal. C-terminal half of trypomastigote type is tandem repeats of 12 amino acid unit and these are followed by GPI anchor structure. No these repeat and no GPI exists in epimastigote trans-sialidase. Both of the enzymes consist of several members of gene family.
In these last years, We have analyzed heterogeneity of these trans-sialidase gene family. The sequence analysis of PCR amplified DNA fragments suggested that around half of the genes encode enzymatically inactive type of trans-sialidase and 30 amino acid substitutions were found in this region of 200 amino acid long. The effect of these substitutions to the enzyme activity is also examined using bacterial expression system.
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