Functional investigation of a novel and essential subcellular compartment in Plasmodium falciparum transmission stage parasites
恶性疟原虫传播阶段寄生虫中新型重要亚细胞区室的功能研究
基本信息
- 批准号:10584525
- 负责人:
- 金额:$ 75.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-04 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:3-Dimensional5 year oldBiogenesisBiophysicsBloodCell membraneCellular MorphologyCessation of lifeChildComplexCulicidaeCytoskeletonDefectDevelopmentElectron MicroscopyEpitopesErythrocytesFemaleFilamentFutureGene ProteinsGenesGoalsHumanImageImmunofluorescence ImmunologicInfectionIngestionIntermediate FilamentsInvestigationIonsKnock-outLabelLife Cycle StagesMalariaMeasuresMembraneMicrofabricationMicrotubulesMolecularMorbidity - disease rateMorphologyMultiprotein ComplexesNamesParasitesPathway interactionsPlasmodium falciparumPlatinumPopulationProcessProteinsScanning Electron MicroscopySeriesShapesTechniquesTestingTransgenic OrganismsTransmission Electron MicroscopyVesicleVisualizationWidthasexualimprovedknock-downmalemembermortalitynovelnovel strategiesresiliencereverse geneticstransmission process
项目摘要
PROJECT SUMMARY
Malaria is an important cause of illness and death worldwide, with most of these deaths resulting from
Plasmodium falciparum infection. Successful completion of the P. falciparum life cycle and infection of a
new human host requires transmission. During the asexual blood stage in human red blood cells, a small
population of parasites differentiates into transmission forms known as gametocytes. These gametocytes
can complete the sexual stage of the parasite life cycle following ingestion by a mosquito. Gametocyte
maturation in human red blood cells occurs over 10-12 days and is associated with major changes in
cellular morphology and rigidity. A newly discovered protein PfBLEB (for Baso-Lateral Expansion Boundary)
is essential for mature gametocyte formation. In asexual parasites, PfBLEB is part of the basal complex, a
ring-like multi-protein complex at the leading edge of the inner membrane complex. While PfBLEB is
dispensable for both asexual replication and gametocyte commitment, it is essential for gametocyte
development. PfBLEB-knockdown or knockout gametocytes arrest during maturation and are non-
transmissible. Furthermore, the PfBLEB-deficient gametocytes have gross morphologic changes with
defects in major cytoskeletal features of the maturing transmission-stage parasite, including the inner
membrane complex and subpellicular microtubules.
In gametocytes with normal PfBLEB expression, PfBLEB defines a new subcellular compartment within the
parasite, demarcating the regions of the parasite plasma membrane that are devoid of the underlying inner
membrane complex. The PfBLEB-compartment is essential for gametocyte development, but the function
and protein constituents of this newly discovered subcellular compartment remain unknown. The goal of the
current application is to define and genetically evaluate the protein components of the PfBLEB compartment
and to understand the functional defects in PfBLEB-deficient gametocytes. The first aim will utilize proximity
labeling and reverse genetics to explore the PfBLEB-containing compartment. The second aim will utilize
multiple imaging and microfabrication techniques to gain a functional understanding of what processes are
abnormal in PfBLEB-deficient gametocytes. Together, the proposed studies will add a new layer to our
molecular understanding of gametocyte development in P. falciparum.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JEFFREY D DVORIN其他文献
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{{ truncateString('JEFFREY D DVORIN', 18)}}的其他基金
Functional characterization of striated fiber assemblins in malaria parasites
疟疾寄生虫中横纹纤维组装体的功能特征
- 批准号:
10675782 - 财政年份:2023
- 资助金额:
$ 75.31万 - 项目类别:
Functional investigation of a novel and essential subcellular compartment in Plasmodium falciparum transmission stage parasites
恶性疟原虫传播阶段寄生虫中新型重要亚细胞区室的功能研究
- 批准号:
10458816 - 财政年份:2022
- 资助金额:
$ 75.31万 - 项目类别:
Molecular mechanisms of schizogony in malaria parasites
疟原虫分裂的分子机制
- 批准号:
10620476 - 财政年份:2019
- 资助金额:
$ 75.31万 - 项目类别:
Molecular mechanisms of schizogony in malaria parasites
疟原虫分裂的分子机制
- 批准号:
10161727 - 财政年份:2019
- 资助金额:
$ 75.31万 - 项目类别:
Molecular mechanisms of schizogony in malaria parasites
疟原虫分裂的分子机制
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10627871 - 财政年份:2019
- 资助金额:
$ 75.31万 - 项目类别:
Molecular mechanisms of schizogony in malaria parasites
疟原虫分裂的分子机制
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9797203 - 财政年份:2019
- 资助金额:
$ 75.31万 - 项目类别:
Molecular mechanisms of schizogony in malaria parasites
疟原虫分裂的分子机制
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- 资助金额:
$ 75.31万 - 项目类别:
Essential gene discovery in the malaria parasite Plasmodium falciparum
疟原虫恶性疟原虫中重要基因的发现
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8564839 - 财政年份:2013
- 资助金额:
$ 75.31万 - 项目类别:
Molecular characterization and substrate identification of malaria kinase PfCDPK5
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$ 75.31万 - 项目类别:
Molecular analysis of a kinase essential for replication of Plasmodium falciparum
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