Functional Analysis of Novel Components of the Toxoplasma Inner Membrane Complex
弓形虫内膜复合物新成分的功能分析
基本信息
- 批准号:10444432
- 负责人:
- 金额:$ 44.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-08-01 至 2026-12-31
- 项目状态:未结题
- 来源:
- 关键词:AblationAcylationAffectAlveolarAlveolusAnimalsApicalApicomplexaArchitectureBindingBiotinylationC-terminalCell membraneCellsCellular biologyCoccidiosisCoiled-Coil DomainComplementComplexConeCryo-electron tomographyCytoskeletal FilamentsCytoskeletonDaughterDiseaseEimeria tenellaElementsFalciparum MalariaFundingGrantHumanInvadedLeadLife StyleMediatingMedicalMembraneMicrotubulesMolecularMotorNamesNeospora caninumOrganellesParasitesPatternPeripheralPlayProcessProteinsProteomeReportingRoleSeriesStructureSurgical suturesSystemToxoplasmaToxoplasma gondiiToxoplasmosisVesicleWorkbasecell motilitycrosslinkdaughter celldesignhuman pathogenin vivoknock-downknockout genemembernew therapeutic targetnovelnovel therapeuticsobligate intracellular parasitepathogenprotein complexprotein functionscaffoldunnatural amino acids
项目摘要
PROJECT SUMMARY
Toxoplasma gondii and related apicomplexan parasites contain a specialized organelle called the inner
membrane complex (IMC) that plays essential roles in host cell invasion and daughter cell formation. The IMC
consists of flattened membrane vesicles and a supporting cytoskeletal meshwork that is flanked by the plasma
membrane and subpellicular microtubules at the periphery of the parasite. Recent in vivo biotinylation (BioID)
studies have revealed a surprising level of compartmentalization within the IMC organelle, with distinct groups
of proteins segregating to the cone-shaped apical cap, the body, or to the basal complex of both the cytoskeletal
and membrane subcompartments. Analyses from our group and others have exposed new essential functions
of the IMC including the role of the apical cap complex AC9/AC10/ERK7 in mounting the conoid which is essential
for organelle secretion and invasion as well as the conserved early daughter bud protein IMC32 that is essential
for replication. In this renewal, we will expand on these studies to determine precisely how these and other critical
IMC components are able to carry out their functions. First, we will determine the role of novel apical cap proteins
that are putative interactors of the AC9/AC10/ERK7 complex and assess their role in apical cap function and
conoid assembly. We will then explore how IMC32 collaborates with the newly discovered partner IMC48 to
function at the earliest stages of parasite division and use these proteins to further explore the early daughter
bud proteome. Finally, we will exploit our recently developed photoreactive unnatural amino acid system as well
as cryo-electron tomography to determine how critical alveolins of the parasite cytoskeleton are organized to
serve as scaffolds for the organelle. Together, this project will promote a much deeper understanding of the
architecture and function of the Toxoplasma IMC. As this organelle is parasite-specific and not present in its
human host, determining precisely how these essential IMC components function promises to enable the design
of novel therapies against T. gondii and other apicomplexan parasites.
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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Peter John Bradley其他文献
Peter John Bradley的其他文献
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{{ truncateString('Peter John Bradley', 18)}}的其他基金
Functional Analysis of Novel Components of the Toxoplasma Inner Membrane Complex
弓形虫内膜复合物新成分的功能分析
- 批准号:
9533992 - 财政年份:2017
- 资助金额:
$ 44.88万 - 项目类别:
Functional Analysis of Novel Components of the Toxoplasma Inner Membrane Complex
弓形虫内膜复合物新成分的功能分析
- 批准号:
9384311 - 财政年份:2017
- 资助金额:
$ 44.88万 - 项目类别:
Functional Analysis of Novel Components of the Toxoplasma Inner Membrane Complex
弓形虫内膜复合物新成分的功能分析
- 批准号:
10550156 - 财政年份:2017
- 资助金额:
$ 44.88万 - 项目类别:
Novel Dense Granule Protein Function in the Chronic Toxoplasma Infection
慢性弓形虫感染中的新型致密颗粒蛋白功能
- 批准号:
9221240 - 财政年份:2016
- 资助金额:
$ 44.88万 - 项目类别:
Novel Dense Granule Protein Function in the Chronic Toxoplasma Infection
慢性弓形虫感染中的新型致密颗粒蛋白功能
- 批准号:
9141001 - 财政年份:2016
- 资助金额:
$ 44.88万 - 项目类别:
Reconstitution of Plasmodium Export in Toxoplasma
弓形虫中疟原虫输出的重建
- 批准号:
8463994 - 财政年份:2012
- 资助金额:
$ 44.88万 - 项目类别:
Novel rhoptry effector proteins in Toxoplasma host-pathogen interaction
弓形虫宿主-病原体相互作用中的新型棒状体效应蛋白
- 批准号:
8229898 - 财政年份:2012
- 资助金额:
$ 44.88万 - 项目类别:
Reconstitution of Plasmodium Export in Toxoplasma
弓形虫中疟原虫输出的重建
- 批准号:
8356983 - 财政年份:2012
- 资助金额:
$ 44.88万 - 项目类别:
Novel rhoptry effector proteins in Toxoplasma host-pathogen interaction
弓形虫宿主-病原体相互作用中的新型棒状体效应蛋白
- 批准号:
8416941 - 财政年份:2012
- 资助金额:
$ 44.88万 - 项目类别:
The Role of Toxoplasma Rhoptries in Host Cell Infection
弓形虫在宿主细胞感染中的作用
- 批准号:
7153481 - 财政年份:2005
- 资助金额:
$ 44.88万 - 项目类别:
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