Core 4 Sali Echeverria
核心 4 萨利·埃切维里亚
基本信息
- 批准号:10506986
- 负责人:
- 金额:$ 21.37万
- 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:2022-07-15 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:Affinity ChromatographyAlgorithmsArchitectureBiochemicalBioinformaticsBiologyCD4 Positive T LymphocytesCRISPR/Cas technologyComplexComputer softwareCryoelectron MicroscopyDataData AnalysesData SetDeuteriumDevelopmentGeneticGenetic TranscriptionGoalsHIVHIV InfectionsHIV-1HeterogeneityHumanHydrogenIndividualIntegration Host FactorsLabelLeadMapsMass Spectrum AnalysisMethodsModelingMolecular ConformationPathway interactionsPeptidesPost-Translational Protein ProcessingProteinsProteomicsResolutionServicesStatistical Data InterpretationStructural ModelsStructureSystems BiologyViralVisualizationbasecell typecrosslinkdata integrationdata toolsdensityflexibilitygenome editinggenome-wide analysisimprovedmultiple data typesmutation screeningnetwork modelsopen sourceparticlepathogenprotein complexprotein protein interactionrestraintstructural biologysuccesstool
项目摘要
THE HARC CENTER: HIV ACCESSORY AND REGULATORY COMPLEXES
COMPUTATIONAL CORE
SUMMARY
The overall goal of the Computational Core is to facilitate the analysis and interpretation of multiple data types
across Projects and Cores to characterize the cellular networks, proteins, and protein complexes that influence
HIV replication and latency. We will employ existing bioinformatics and systems biology approaches, as well as
develop new methods to facilitate the unification of mechanistic and structural details with network biology, with
a strong emphasis on the analysis and integration of data derived from proteomics, genetics, and structural
biology approaches. Specifically, we will provide the tools to identify interactions of endogenous proviral and
antiviral HIV-host protein complexes that have been structurally and functionally characterized by the
Proteomics, Genetics, and Structural Biology Cores. This includes datasets from affinity purification mass
spectrometry (AP-MS), native mass spectrometry (nMS), cross-linking mass spectrometry (XL-MS),
hydrogen/deuterium exchange mass spectrometry (H/DX-MS), systematic genome editing by CRISPR-Cas9,
deep mutational scanning (DMS), and cryo-electron microscopy (cryo-EM). These datasets will be analyzed
separately as well as jointly, followed by visualization to gain a deeper understanding of the functional pathways
that are modulated during HIV infection. Finally, we will determine the structures of HIV-human protein
complexes by an integrative approach using various proteomics, genetics, structural, and biochemical data.
Integrative structure determination will be performed using the open-source Integrative Modeling Platform (IMP)
package developed in the Sali lab (Core Lead). We will initially focus on protein complexes containing human or
simian A3Gs, and HIV-1 Vif, Rev, and Tat, followed by structure determination of HIV-human complexes
identified from CD4+ T cells and structurally interrogated by the Proteomics Core.
HARC中心:HIV附件和调控复合体
计算核心
摘要
计算核心的总体目标是促进对多种数据类型的分析和解释
跨项目和核心来表征影响细胞网络、蛋白质和蛋白质复合体
艾滋病毒复制和潜伏期。我们将利用现有的生物信息学和系统生物学方法,以及
开发新的方法,以促进机械和结构细节与网络生物学的统一,
非常重视对来自蛋白质组学、遗传学和结构学的数据进行分析和整合
生物学走近了。具体地说,我们将提供工具来识别内源性前病毒和
抗病毒HIV-宿主蛋白复合体的结构和功能特征
蛋白质组学、遗传学和结构生物学的核心。这包括来自亲和纯化质量的数据集
光谱分析(AP-MS)、天然质谱学(NMS)、交联质谱(XL-MS)、
氢/氢交换质谱仪(H/DX-MS),CRISPR-Cas9系统基因组编辑,
深突变扫描(DMS)和冷冻电子显微镜(Cryo-EM)。将对这些数据集进行分析
分别和联合,然后可视化,以获得对功能途径的更深层次的理解
在HIV感染过程中受到调节。最后,我们将确定HIV-人类蛋白的结构
通过使用各种蛋白质组学、遗传学、结构和生化数据的综合方法来合成复合体。
将使用开源集成建模平台(IMP)执行集成结构确定
在SARI实验室开发的包(核心领导)。我们首先将重点放在含有人或
猿猴A3Gs和HIV-1 Vif、REV和Tat,以及HIV-人类复合体的结构测定
从CD4+T细胞中鉴定出来,并由蛋白质组学核心进行结构分析。
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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ANDREJ SALI其他文献
ANDREJ SALI的其他文献
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{{ truncateString('ANDREJ SALI', 18)}}的其他基金
CORE 1: Data Management and Bioinformatics Core
核心 1:数据管理和生物信息学核心
- 批准号:
10549998 - 财政年份:2018
- 资助金额:
$ 21.37万 - 项目类别:
TR&D Project 4. The Imaging Stage: Multiscale Spatiotemporal Modeling of Macromolecular Systems in Cellular Neighborhoods
TR
- 批准号:
10401763 - 财政年份:2014
- 资助金额:
$ 21.37万 - 项目类别:
TR&D Project 4. The Imaging Stage: Multiscale Spatiotemporal Modeling of Macromolecular Systems in Cellular Neighborhoods
TR
- 批准号:
10621361 - 财政年份:2014
- 资助金额:
$ 21.37万 - 项目类别:
DETERMINATION OF THE PSEUDO-ATOMIC STRUCTURE OF NUCLEAR PORE COMPLEX (NPC) COMPO
核孔复合体(NPC)复合物拟原子结构的测定
- 批准号:
8362329 - 财政年份:2011
- 资助金额:
$ 21.37万 - 项目类别:
DEVELOPMENT AND TESTING OF MODELLER, AND RELATED TOOLS, ON THE ALPHA PLATFORM
在 ALPHA 平台上开发和测试 MODELER 及相关工具
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主轴极体铁芯结构的计算模型
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8365787 - 财政年份:2011
- 资助金额:
$ 21.37万 - 项目类别:
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