Evolution of Cryptococcus neoformans Strains from Patients with HIV/AIDS
Evolution of Cryptococcus neoformans Strains from Patients with HIV/AIDS
批准号:
9981611
负责人:
John R. Perfect
金额:
$34.76万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2011
资助国家:
美国
项目状态:
已结题
起止时间:
2011-08-05 至 2023-06-30
关键词:
AIDS populationAIDS/HIV problemAgeAnimal ModelAnimalsAntifungal AgentsBasic ScienceBehaviorBioinformaticsBiological AssayBrain DiseasesCell SizeCell WallCell membraneCellsCensusesCentral Nervous System DiseasesCentral Nervous System InfectionsCessation of lifeClinicalCommunitiesComplexCountryCryptococcal MeningitisCryptococcosisCryptococcusCryptococcus neoformansDataDiseaseDisease OutcomeDrug TargetingDrug resistanceEncapsulatedEnvironmentEvolutionExplosionFutureG CellsGenesGeneticGenetic CrossesGenetic TranscriptionGenomeGenomicsGenotypeGoalsGrowthHealth Care CostsHealthcare SystemsHigh temperature of physical objectHumanImmune responseImmunocompromised HostIn VitroInfectionInfrastructureInternetInvestigationKnowledgeLibrariesLinkLung diseasesMelaninsMeningitisMetabolicMolecularMorbidity - disease rateMovementMusOryctolagus cuniculusOutcomePartner in relationshipPathogenesisPathogenicityPathway interactionsPatientsPhagocytosisPhenotypePhylogenetic AnalysisPlaguePopulationPopulations at RiskProductionRecording of previous eventsResearchResourcesRiskSpottingsStructure of thyroid parafollicular cellSystemTreatment ProtocolsValidationVirulenceVirulentWorkYeastsaggressive therapyantiretroviral therapybasecell capsulecostdesignfitnessfungusgenetic linkagegenetic pedigreegenome sciencesgenome sequencinggenome wide association studygenomic datagenomic locushealth care availabilityhuman datahuman diseasehuman pathogeninsightmortalityoutcome forecastpathogenpathogenic fungusphenotypic datapopulation genetic structurepublic health relevanceresponserobotic systemscreeningstressorsugartooltreatment strategywhole genome
中文摘要
摘要
这种竞争性的更新将继续致力于了解种群遗传结构,
新型隐球菌。有了这个庞大的基因组测序数据,我们将扩大它,并添加一个功能
和/或平移聚焦。重要的是,将序列数据与表型数据、动物模型
和人类感染结果,以帮助了解使其成为致命人类的遗传成分,
新型隐球菌代表了一组被包裹的担子菌酵母,
每年产生数十万例脑膜炎病例,死亡率为15%至50%以上,
这取决于卫生保健系统,目前还没有发现新的抗真菌药物用于治疗,
25年在这个建议中,我们将使用全基因组序列来指导一个研究平台,
在问题中提出的具体目标。具体目标1是:什么是基因型和表型
临床和环境菌株之间的差异。具体目标2审查了以下内容
问题:在已经产生疾病的临床分离株中,为什么有些菌株更容易感染
比其他人更恶毒或更具攻击性?这项建议有三个目标。第一,使用全基因组
测序(WGS)和GWAS在大量的菌株链接到功能数据,以拨号到
野生型菌株,并找到特定的基因和/或网络重要的C.新形式的健身/生存在
哺乳动物宿主因此,我们将确定潜在的弱点,在真菌用于抗真菌药物
目标的第二,从基因上鉴定出产生更具侵略性疾病行为的“坏演员”菌株,
从而基于此调整治疗方案
了解菌株的病理学最后,这项研究将创造一个实质性的基础设施,
一个充分表征的野生型菌株库,供整个隐球菌社区将来使用
病理生物学工作。
英文摘要
Abstract
This competitive renewal will continue to work on understanding the population genetic structures of
Cryptococcus neoformans. With this massive genome sequencing data, we will expand it and add a functional
and/or translational focus. Importantly, the sequence data are integrated with phenotypic data, animal models
and human infection outcomes to help understand the genetic components that make it a deadly human
pathogen.Cryptococcus neoformans represents a group of encapsulated basidiomycetous yeasts that continue
to produce hundreds of thousands of cases of meningitis each year with mortality rates of 15 to over 50%
depending on the health care systems and no new antifungal agents have been discovered for its treatment in
25 years. In this proposal, we will use whole genome sequences to direct a research platform to complete two
Specific Aims that are framed in questions. Specific Aim 1 is: What are the genotypic and phenotypic
differences between clinical and environmental strains. Specific Aim 2 examines the following
question: Within clinical isolates that have already produced disease, why are some strains more
virulent or aggressive than others? The goal of this proposal is three- fold. First, to use whole genome
sequencing (WGS) and GWAS in a large number of strains linked to functional data in order to dial down into
wild-type strains and find specific genes and/or networks important to C. neoformans fitness/survival in the
mammalian host. Thus, we will identify potential weak spots in the fungus to be used for antifungal drug
targets. Second, to genetically identify “bad actor” strains producing more aggressive disease behaviors that
could be identified for the treating clinician to appreciate and thus adjust treatment regimens based on this
knowledge of the strain’s pathobiology. Finally, this study will create a substantial infrastructure addition of a
library of well-characterized wild-type strains for use by the entire cryptococcal community for future
pathobiology work.
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Administrative Core
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批准号:8931200
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项目类别:
-
资助金额:$9.05万
-
财政年份:2015
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负责人:John R. Perfect
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依托单位:
Transdisciplinary Program to Identify Novel Antifungal Targets and Inhibitors
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批准号:9272329
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项目类别:
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资助金额:$180.35万
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财政年份:2015
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负责人:John R. Perfect
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依托单位:
Evolution of Cryptococcus neoformans strains from patients with HIV/AIDS
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批准号:8511334
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项目类别:
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资助金额:$42.87万
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财政年份:2011
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负责人:John R. Perfect
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依托单位:
Evolution of Cryptococcus neoformans Strains from Patients with HIV/AIDS
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批准号:10199975
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项目类别:
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资助金额:$37.42万
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财政年份:2011
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负责人:John R. Perfect
-
依托单位:
Evolution of Cryptococcus neoformans strains from patients with HIV/AIDS
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批准号:8889613
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项目类别:
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资助金额:$30.03万
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财政年份:2011
-
负责人:John R. Perfect
-
依托单位:
Evolution of Cryptococcus neoformans strains from patients with HIV/AIDS
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批准号:8701226
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项目类别:
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资助金额:$30.03万
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财政年份:2011
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负责人:John R. Perfect
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依托单位:
Evolution of Cryptococcus neoformans Strains from Patients with HIV/AIDS
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批准号:10424470
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项目类别:
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资助金额:$36.39万
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财政年份:2011
-
负责人:John R. Perfect
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依托单位:
Evolution of Cryptococcus neoformans strains from patients with HIV/AIDS
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批准号:8313864
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项目类别:
-
资助金额:$50.67万
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财政年份:2011
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负责人:John R. Perfect
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依托单位:
Pathobiology of C. neoformans in the Central Nervous System
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批准号:8099990
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项目类别:
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资助金额:$14.43万
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财政年份:2010
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负责人:John R. Perfect
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依托单位:
Pathobiology of C. neoformans in the Central Nervous System
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批准号:8237066
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项目类别:
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资助金额:$38.22万
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财政年份:2008
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负责人:John R. Perfect
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依托单位:
Pathobiology of C. neoformans in the Central Nervous System
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批准号:9274901
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项目类别:
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资助金额:$45.74万
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财政年份:2008
-
负责人:John R. Perfect
-
依托单位:
Pathobiology of C. neoformans in the Central Nervous System
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批准号:8759107
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项目类别:
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资助金额:$45.8万
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财政年份:2008
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负责人:John R. Perfect
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依托单位:
Pathobiology of C. neoformans in the Central Nervous System
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批准号:7460500
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项目类别:
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资助金额:$38.62万
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财政年份:2008
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负责人:John R. Perfect
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依托单位:
Pathobiology of C. neoformans in the Central Nervous System
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批准号:9489144
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项目类别:
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资助金额:$47.51万
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财政年份:2008
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负责人:John R. Perfect
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依托单位:
Pathobiology of C. neoformans in the Central Nervous System
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批准号:7559532
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项目类别:
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资助金额:$39.0万
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财政年份:2008
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负责人:John R. Perfect
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依托单位:
Pathobiology of C. neoformans in the Central Nervous System
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批准号:7777388
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项目类别:
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资助金额:$38.61万
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财政年份:2008
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负责人:John R. Perfect
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依托单位:
Pathobiology of C. neoformans in the Central Nervous System
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批准号:8036970
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项目类别:
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资助金额:$38.22万
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财政年份:2008
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负责人:John R. Perfect
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依托单位:
Pathobiology of C. neoformans in the Central Nervous System
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批准号:8866352
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项目类别:
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资助金额:$45.69万
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财政年份:2008
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负责人:John R. Perfect
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依托单位:
HOST TEMPERATURE GROWTH OF C NEOFORMANS
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批准号:6299764
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项目类别:
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资助金额:$15.15万
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财政年份:2000
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负责人:John R. Perfect
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依托单位:
CRYPTOCOCCUS NEOFORMANS--A MODEL FOR PATHOGENIC FUNGI
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批准号:6362399
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项目类别:
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资助金额:$80.52万
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财政年份:1999
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负责人:John R. Perfect
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依托单位: