Proteomics core
蛋白质组学核心
基本信息
- 批准号:10512626
- 负责人:
- 金额:$ 476.91万
- 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:2022-05-16 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:ADP ribosylationAdenosine Diphosphate RiboseAntiviral AgentsBindingBiologicalBiological AssayBiologyCOVID-19Cell Culture TechniquesCell modelCellsCellular AssayComplexCryoelectron MicroscopyDataDetectionDeuteriumDevelopmentDiseaseDrug InteractionsDrug TargetingEffectivenessFutureGoalsHealthcareHospitalsHydrogenImmune responseIn VitroIndividualInfectionInfrastructureInstitutesInterferonsLeadMass Spectrum AnalysisMeasurementMeasuresMethodologyMethodsModelingMolecularMonitorNatureNonstructural ProteinOralOrganismOutcomePeptide HydrolasesPharmaceutical PreparationsPharmacotherapyPhysiologicalPlayPost-Translational Protein ProcessingProteinsProteomicsRecombinantsReproducibilityResearchRoleSeverity of illnessSignal TransductionSpecificityStructureSystemTechnologyTherapeuticTimeVariantVial deviceViralViral PhysiologyViral ProteinsVirusWorkX-Ray Crystallographyassay developmentbasecrosslinkdesigndrug candidatedrug developmentdrug discoveryflexibilityhigh riskin vivoin vivo Modelinterestmultiplex assaynovelpandemic diseasepolypeptideprogramsprotein complexprotein expressionprotein structureresponsescreeningsmall moleculestoichiometrystructural biologysuccesstoolvirology
项目摘要
CORE 8: PROTEOMICS
SUMMARY
Readily distributed, orally bioavailable small molecule antiviral agent could play an outsized role not only in the
response to COVID-19, but also to future pandemics by reducing the severity of disease for those at highest risk
for serious outcomes, and by curtailing the strain that serious illness puts on hospitals and healthcare
infrastructure. Determining the molecular mechanism of biologically active viral proteins is a critical component
to a successful drug development pipeline. Proteomics approaches represent a critical tool for the study of viral
biology and drug development pipelines due to the capacity to assess viral protein activity in living cells using
high-throughput multiplexed assays. Furthermore, the agnostic nature of protein detection allows for proteomics
assays to be rapidly adapted to different viruses or host organisms.
The work proposed by this core will be performed at the Thermo Fisher Scientific Proteomics Facility for Disease
Target Discovery located at the J. David Gladstone Institutes at the UCSF campus. This facility and the
Proteomics Core, will be led by Dr. Swaney, an expert in mass-spectrometry based proteomics research with
a track record in the development and application of novel proteomics approaches to enable biological discovery.
Within the QCRG Pandemic Response Program, the goal of the Proteomics Core is to provide high-quality,
accurate, and reproducible proteomic analyses that measure viral proteins and their cellular activities. This will
enable the QCRG Drug Discovery Platform to design and identify lead compounds and develop effective cell-
based assays that measure drug candidate effectiveness in living cells. The proteomics assays described in this
core are essential to the success of the QCRG Pandemic Response Program and will support all Projects, as
well as the Screening Core, Integrative Modeling Core, and the In Vivo and In Vitro Virology Cores.
Efforts of the Proteomics Core will include measuring the direct effect that drugs have on viral protein
abundance and post-translational modifications during infection time courses in physiologically relevant cell
models, and drug target specificity using cellular thermal shift assays. To aid flexible structure determination and
viral protein assembly in cells and recombinant expression systems, we will also provide structural proteomics
approaches to measure subunit stoichiometry, domain topology, and protein and drug interaction interfaces.
Finally, we will develop assays to measure viral protein activity, including an ADP-ribosylation assay to measure
macrodomain activity, and a protease cleavage assay to measure vial protease proteolytic activity.
核心8:蛋白质组学
总结
易于分布的、口服生物可利用的小分子抗病毒剂不仅可以在抗病毒治疗中发挥巨大作用,
应对COVID-19,以及通过降低最高风险人群的疾病严重程度来应对未来的大流行病
并通过减少严重疾病给医院和医疗保健带来的压力
基础设施演进确定生物活性病毒蛋白的分子机制是一个关键组成部分
一个成功的药物研发管道蛋白质组学方法是研究病毒感染的重要工具。
生物学和药物开发管道,因为有能力评估活细胞中的病毒蛋白活性,
高通量多重测定。此外,蛋白质检测的不可知性允许蛋白质组学
检测方法可快速适应不同的病毒或宿主生物。
该核心提出的工作将在Thermo Fisher Scientific Proteomics Facility for Disease
目标发现位于加州大学旧金山分校校园的J.大卫格莱斯顿研究所。这个设施和
蛋白质组学核心将由Swaney博士领导,他是基于质谱的蛋白质组学研究专家,
在开发和应用新的蛋白质组学方法以实现生物发现方面的记录。
在QCRG大流行应对计划中,蛋白质组学核心的目标是提供高质量,
准确和可重复的蛋白质组学分析,测量病毒蛋白及其细胞活性。这将
使QCRG药物发现平台能够设计和识别先导化合物,并开发有效的细胞-
基于测定候选药物在活细胞中的有效性的测定。本文中描述的蛋白质组学测定法
核心是QCRG流行病应对计划成功的关键,并将支持所有项目,
以及筛选核心,综合建模核心,体内和体外病毒学核心。
蛋白质组学核心的工作将包括测量药物对病毒蛋白的直接影响
在生理相关细胞中感染时间过程中的丰度和翻译后修饰
模型和使用细胞热位移测定的药物靶点特异性。为了帮助确定柔性结构,
细胞和重组表达系统中的病毒蛋白质组装,我们还将提供结构蛋白质组学
测量亚基化学计量、结构域拓扑以及蛋白质和药物相互作用界面的方法。
最后,我们将开发检测病毒蛋白活性的方法,包括ADP-核糖基化检测,
大结构域活性,和蛋白酶切割测定以测量小瓶蛋白酶蛋白水解活性。
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)
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Danielle L Swaney其他文献
Danielle L Swaney的其他文献
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{{ truncateString('Danielle L Swaney', 18)}}的其他基金
A universal multiplexing approach to unlock the hidden proteome
解锁隐藏蛋白质组的通用多重方法
- 批准号:
10240468 - 财政年份:2019
- 资助金额:
$ 476.91万 - 项目类别:
A universal multiplexing approach to unlock the hidden proteome
解锁隐藏蛋白质组的通用多重方法
- 批准号:
10478967 - 财政年份:2019
- 资助金额:
$ 476.91万 - 项目类别: