Development and maintenance of chronic toxoplasmosis
Development and maintenance of chronic toxoplasmosis
批准号:
10374148
负责人:
Sebastian Lourido
金额:
$67.13万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-03-17 至 2026-02-28
关键词:
5&apos Untranslated RegionsAddressBindingBrainCRISPR screenCategoriesCell Culture TechniquesChromatinChronicComplementCystDataDevelopmentDiseaseDisease ReservoirsDown-RegulationElementsEnvironmental Risk FactorEventExposure toFailureFoundationsFutureGenesGeneticGenetic TranscriptionGoalsHomeostasisImmunocompetentImmunocompromised HostIndividualInfectionLesionLicensingLifeLinkMaintenanceMediatingMessenger RNAMolecularMonitorMusMutation AnalysisNational Institute of Allergy and Infectious DiseaseNucleic Acid BindingParasitesPathway interactionsPopulationPrevalenceProcessProteinsProteomicsRNARecurrenceRegulationRegulatory PathwayReporterResistanceResolutionRibosomesRoleStressStructureTissuesToxoplasmaToxoplasma gondiiToxoplasmosisTranscriptTranscriptional RegulationTranslational RegulationTranslationsVideo MicroscopyVirulenceWorkacute infectionalkalinitybasebiodefensecurative treatmentsinsightmouse modelpreventprogramspromoterresponseribosome profilingscreeningtranscription factortranscriptome sequencing
中文摘要
7.项目摘要/摘要
慢性弓形虫感染广泛存在,它们的重新激活可导致危及生命的疾病
免疫功能低下的个体和复发性眼部病变中的免疫活性。最近确认的
慢性分化的主要调节因子BFD1提供了前所未有的机会来研究
建立和维持慢性弓形虫感染的分子事件。BFD1对于慢性疾病是必要的
在细胞培养和小鼠感染模型中的分化,其表达足以诱导慢性
差异化。与慢性阶段维护期间对BFD1的持续需求一致,
在有条件下调BFD1的情况下,分化程序被逆转。初步结果表明,BFD1
是通过其5‘UTR转录后控制的,导致假设BFD1的翻译调控
是弓形虫慢性阶段发育和维持的基础。这项提议寻求将
通过三个相辅相成的目标将BFD1纳入更广泛的监管网络。目标1将检查序列
介导BFD1翻译的元件、二级RNA结构和核糖体占据动力学
监管。目标2将使用BFD1的条件性缺失来表征转录和蛋白质组的变化
调节再激活,以及维持分化状态的分子回路。最后,目标3将延长
通过筛选参与BFD1翻译调控的基因来控制分化的调控途径
进一步检测BFD1直接调控的转录因子的功能。这件事的首要目标是
综合分析是了解促进慢性分化的条件,并许可
弓形虫病治疗方法的发展。
英文摘要
7. PROJECT SUMMARY/ABSTRACT
Chronic Toxoplasma gondii infections are widespread and their reactivation can cause life-threatening disease in
immunocompromised individuals and recurrent ocular lesions in the immunocompetent. The recently identified
master regulator of chronic differentiation, BFD1, provides an unprecedented opportunity to investigate the
molecular events that establish and maintain chronic T. gondii infections. BFD1 is necessary for chronic
differentiation in cell culture and in mouse models of infection, and its expression is sufficient to induce chronic
differentiation. Consistent with a sustained requirement for BFD1 during chronic stage maintenance, the
differentiation program is reversed upon conditional down-regulation of BFD1. Preliminary results indicate that BFD1
is post-transcriptionally controlled through its 5′ UTR, leading to the hypothesis that translational regulation of BFD1
is fundamental to the development and maintenance of chronic T. gondii stages. This proposal seeks to integrate
BFD1 into a broader regulatory network through three complementary aims. Aim 1 will examine the sequence
elements, secondary RNA structures, and ribosomal occupancy dynamics that mediate BFD1 translational
regulation. Aim 2 will use conditional depletion of BFD1 to characterize transcriptional and proteomic changes that
mediate reactivation, and the molecular circuits that maintain the differentiated state. Finally, Aim 3 will extend the
regulatory pathways that control differentiation by screening for genes involved in the translational regulation of BFD1
and further examining the function of transcription factors directly regulated by BFD1. The overarching goal of this
comprehensive analysis is to understand the conditions that promote chronic differentiation and license the
development of curative therapies against toxoplasmosis.
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Development and maintenance of chronic toxoplasmosis
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批准号:10181740
-
项目类别:
-
资助金额:$68.25万
-
财政年份:2021
-
负责人:Sebastian Lourido
-
依托单位:
Development and maintenance of chronic toxoplasmosis
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批准号:10579245
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项目类别:
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资助金额:$65.98万
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财政年份:2021
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负责人:Sebastian Lourido
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项目类别:
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资助金额:$48.75万
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Control of parasite invasion by a microneme protein complex conserved in Apicomplexans
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资助金额:$48.75万
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负责人:Sebastian Lourido
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Control of parasite invasion by a microneme protein complex conserved in Apicomplexans
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批准号:10062827
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资助金额:$48.75万
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批准号:9203042
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资助金额:$24.38万
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财政年份:2016
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负责人:Sebastian Lourido
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依托单位:
Dissecting essential signaling pathways in apicomplexan parasites
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批准号:8609230
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资助金额:$48.75万
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财政年份:2013
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负责人:Sebastian Lourido
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依托单位:
Dissecting essential signaling pathways in apicomplexan parasites
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批准号:8737992
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项目类别:
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资助金额:$48.75万
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财政年份:2013
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负责人:Sebastian Lourido
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依托单位:
Dissecting essential signaling pathways in apicomplexan parasites
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批准号:9349383
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项目类别:
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资助金额:$48.75万
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财政年份:2013
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负责人:Sebastian Lourido
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依托单位:
Dissecting essential signaling pathways in apicomplexan parasites
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批准号:9136678
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项目类别:
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资助金额:$48.75万
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财政年份:2013
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负责人:Sebastian Lourido
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依托单位:
海外基金