Detection and tissue destribution of CWD and BSE PrPSc
CWD 和 BSE PrPSc 的检测和组织分布
基本信息
- 批准号:8307861
- 负责人:
- 金额:$ 30.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:AddressAffectAnimal DiseasesAnimalsAreaBasic ScienceBiochemicalBiologicalBiological AssayBladderBlindedBloodBlood specimenBovine Spongiform EncephalopathyBrainBrain StemBuffersCattleCell Surface ProteinsCharacteristicsChronic Wasting DiseaseClinicalCreutzfeldt-Jakob SyndromeDataDeerDetectionDevelopmentDiagnosisDiagnosticDiagnostic testsDiseaseDrug or chemical Tissue DistributionEarly DiagnosisEnvironmentEquilibriumExhibitsFecesFood ChainGlycoproteinsGoalsHamstersHealthHeartHumanIn VitroIncubatedInfectionInfectious AgentIntestinesKidneyLiquid substanceLiverLungLymphoidMeasuresMethodologyMethodsMusMuscleNamesNervous system structureNeuraxisNormal CellNorth AmericaOrganOutcomePathogenesisPeripheralPeripheral NervesPhasePoaceaePrPPrPSc ProteinsPrevalencePrincipal InvestigatorPrion DiseasesPrionsProceduresProcessPropertyProtein IsoformsProteinsProtocols documentationReactionRelative (related person)Replication-Associated ProcessReportingResearchRiskRisk AssessmentRouteSalivaSamplingScrapieSensitivity and SpecificitySheepSkinSoilSonicationSourceSpeedSpinal CordSpleenStagingStomachSurrogate MarkersSurveysTechnologyTestingTimeTime StudyTissuesTransgenic MiceTubeUrineWestern Blottinganimal tissueassay developmentbasecervidexperiencein vivomouse modelpreventprocess optimizationprogramsprotein misfolding cyclic amplificationresearch studysingle moleculesoil samplingtransmission process
项目摘要
Transmissible spongiform encephalopathies (TSEs) are a group of fatal diseases affecting humans and
animals, including Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, bovine spongiform
encephalopathy (BSE) in cattle and chronic wasting disease (CWD) in cervids. Prions are the infectious
agent associated to TSEs, which appears to be composed exclusively by a misfolded version of the normal
prion protein (termed PrPSc), and the disease is transmitted by propagation of the misfolding from the
disease associated isoform to the normal host protein (termed PrPc). We have recently described a
procedure to induce the conversion of PrPc into PrPSc in vitro starting with minute quantities of brain PrPSc.
This procedure, named Protein Misfolding Cyclic Amplification (PMCA) mimics the process of prion
replication in vivo, but at an accelerated speed resulting in an exponential amplification of the initial amount
of PrPSc. The major goals of this project are to study the replication of CWD and BSE prions in vitro,
evaluate tissue distributions of infectious protein, enlighten the routes of transmission and develop a
diagnostic assay for CWD and BSE infected animals. In specific aim 1 we will optimize the PMCA
technology for efficient high-sensitivity detection of cattle and deer PrPSc; Specific aim 2 proposes to use the
technology to evaluate the tissue distribution of the infectious agent at different times during the incubation
period in cattle and deer infected animals; In specific aim 3 we will to study the routes of transmission of
CWD by analyzing source of materials (such as soil and grass) from animals' natural environment and
excretory fluids (feces, urine, saliva); Finally specific aim 4 will attempt to develop a sensitive diagnostic test
for BSE and CWD using blood or urine samples. This project offers a balanced combination between basic
science mechanistic studies aimed to understand the most relevant scientific problems in the field of
zoonotic prion disease and applied studies to resolve the main practical problem associated to these
diseases, which is the lack of a highly-sensitive pre-symptomatic diagnosis to limit the spreading of these
incurable illnesses.
传染性海绵状脑病(TSE)是一组影响人类和
动物,包括人类的克雅氏病(CJD),绵羊的瘙痒病,牛海绵状
牛的脑病(BSE)和宫颈的慢性衰弱病(CWD)。普恩病毒是有传染性的
与TSE关联的代理,它似乎完全由错误折叠的正常版本组成
Prion蛋白(称为PrPSc),疾病通过错误折叠的繁殖从
疾病相关的正常宿主蛋白的异构体(称为PrPc)。我们最近描述了一种
从微量的脑PrPSc开始,体外诱导PrPc转化为PrPSc的程序。
这一过程被称为蛋白质错折叠循环扩增(PMCA),它模拟了Pron的过程
体内复制,但速度加快,导致初始量的指数放大
PrPSc.该项目的主要目标是研究CWD和疯牛病病毒的体外复制。
评估感染蛋白的组织分布,启发传播途径,开发
CWD和BSE感染动物的诊断试验。在具体目标1中,我们将优化PMCA
高效高灵敏度检测牛和鹿PrPSc的技术;具体目标2建议使用
在潜伏期不同时间评估感染源的组织分布的技术
在牛和鹿感染动物的时期;在具体目标3中,我们将研究牛和鹿感染的传播途径
CWD通过分析来自动物自然环境的材料来源(如土壤和草)和
排泄液(粪便、尿液、唾液);最后,特定目标4将尝试开发一种灵敏的诊断测试
对于BSE和CWD,使用血液或尿液样本。该项目提供了基本的
科学机械论研究的目的是理解科学领域中最相关的科学问题
人畜共患病和解决与此相关的主要实际问题的应用研究
疾病,即缺乏高度敏感的症状前诊断,以限制这些疾病的传播
不治之症。
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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CLAUDIO SOTO的其他文献
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{{ truncateString('CLAUDIO SOTO', 18)}}的其他基金
Production and Distribution of well-characterized polymorphic variants of alpha-synuclein aggregates
α-突触核蛋白聚集体的充分表征的多态性变体的生产和分布
- 批准号:
10706583 - 财政年份:2022
- 资助金额:
$ 30.47万 - 项目类别:
Production and Distribution of well-characterized polymorphic variants of alpha-synuclein aggregates
α-突触核蛋白聚集体的充分表征的多态性变体的生产和分布
- 批准号:
10549216 - 财政年份:2022
- 资助金额:
$ 30.47万 - 项目类别:
Comprehensive diagnosis of Alzheimer's disease by detection of misfolded oligomers in biological fluids
通过检测生物体液中错误折叠的寡聚物来全面诊断阿尔茨海默病
- 批准号:
9766691 - 财政年份:2019
- 资助金额:
$ 30.47万 - 项目类别:
Cross-seeding of Protein Misfolding as a Disease Mechanism
蛋白质错误折叠作为疾病机制的交叉播种
- 批准号:
8450044 - 财政年份:2012
- 资助金额:
$ 30.47万 - 项目类别:
Cross-seeding of Protein Misfolding as a Disease Mechanism
蛋白质错误折叠作为疾病机制的交叉播种
- 批准号:
8299342 - 财政年份:2012
- 资助金额:
$ 30.47万 - 项目类别:
Absorption, Metabolism and Biodistribution of Prions after Oral Ingestion
口服摄入后朊病毒的吸收、代谢和生物分布
- 批准号:
8439892 - 财政年份:2012
- 资助金额:
$ 30.47万 - 项目类别:
Cross-seeding of Protein Misfolding as a Disease Mechanism
蛋白质错误折叠作为疾病机制的交叉播种
- 批准号:
8829300 - 财政年份:2012
- 资助金额:
$ 30.47万 - 项目类别:
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