| Project/Area Number |
16017272
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Ehime University |
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Principal Investigator |
TORII Motomi Ehime University, School of Medicine, Professor, 医学部, 教授 (20164072)
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| Co-Investigator(Kenkyū-buntansha) |
KANEKO Osamu Ehime University, School of Medicine, Associate Professor, 医学部, 助教授 (50325370)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2005: ¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 2004: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | infectious disease / malaria / Plasmodium / マラリア原虫 / 赤血球結合蛋白質 / レセプター / GPIアンカー |
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| Research Abstract |
Parasitophorous vacuole formation is a critical step for the successful invasion of host erythrocytes by malaria parasite. Rhoptry proteins are believed to have essential roles in vacuole formation, although their biological roles are poorly understood. To understand the molecular interactions between parasite rhoptry proteins and the erythrocyte during invasion, we have characterized the binding specificity of the high molecular mass rhoptry protein (RhopH) complex to erythrocytes using the rodent malaria parasite, Plasmodium yoelii and proposed that the major erythrocyte receptor for PyRhopH complex is a protein attached to the erythrocyte surface via GPI-anchor.
To further characterize and identify the unknown receptor protein, we employed forward genetic analysis using consomic mouse strains derived from C57BL/6J (B6) and MSM/Ms strains based on the difference in the PyRhopH complex binding to the erythrocytes from these mice (erythrocytes from B6 exhibited higher binding than MSM/Ms). These consomic strains have B6 genetic background and a particular chromosome or chromosomal region is replaced with the one from MSM/Ms. A panel of consomic strains available were examined and the binding among consomic strains were found to be not clearly differentiate to B6 type or MSM/Ms type, indicating that multiple factors were involved in the observed binding. However B6-11^<MSM/Ms>, which harbored chromosome 11 derived from MSM/Ms, showed a prominent low binding, even lower than MSM/Ms, thus we considered that the receptor protein potentially located on chromosome 11. Based on this assumption, we are in a process to narrow the candidate region on the chromosome 11 by further linkage analysis between B6 and B6-11^<MSM/Ms>. The GPI-anchored protein on the candidate region would be characterized as a prime candidate for the PyRhopH complex receptor.
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