The NYSGRC: A Large Scale Center for PSI:Biology
The NYSGRC: A Large Scale Center for PSI:Biology
批准号:
8692889
负责人:
STEVEN C. ALMO
金额:
$579.28万
依托单位国家:
美国
项目类别:
财政年份:
2010
资助国家:
美国
项目状态:
已结题
起止时间:
2010-09-01 至 2015-08-31
关键词:
AddressAlgorithmsArchivesAreaAutoimmune DiseasesAutomobile DrivingBiochemicalBiochemistryBioinformaticsBiologicalBiologyBiotechnologyCaliforniaCaringCell LineCell membraneCellular biologyChargeCommitCommunicable DiseasesCommunitiesComplementComplexCoupledCryoelectron MicroscopyCrystallizationDataData CollectionDatabasesDepositionDevelopmentDiseaseElementsEnsureEnzymesEukaryotic CellEvolutionFailureFamilyFundingFutureGenerationsGeneticHealthHomology ModelingHumanHuman ResourcesHybridsIllinoisImmuneIndividualInformaticsInformation DisseminationInsectaInternationalLabelLaboratoriesLeadershipLengthLettersLigand BindingLightLinkMalignant NeoplasmsManualsMedicalMedicineMembrane ProteinsMethodsMissionModelingModificationMolecularNMR SpectroscopyNational Institute of General Medical SciencesNeoplasm MetastasisNew YorkNew York CityNuclear PoreOrthologous GenePathogenesisPharmaceutical PreparationsPhosphoric Monoester HydrolasesPhotonsPlayPositioning AttributePrincipal InvestigatorProcessProductionProductivityProgram Research Project GrantsProtein Structure InitiativeProteinsProtocols documentationQuality ControlRecordsRelianceReportingResearchResearch InfrastructureResearch PersonnelResolutionResourcesRoboticsRoentgen RaysRoleRunningSan FranciscoSeleniumSeriesServicesSesame - dietaryShapesSignal PathwaySolutionsSourceSpecimenSpeedStructural ModelsStructureSupervisionSystemTechnologyTertiary Protein StructureTherapeuticTimeTriageUnited States National Institutes of HealthUniversitiesVisionWashingtonWorkWritingbasebeamlinecollegecombatdata managementdata structuredesigndesign and constructionenzyme structureexperienceexpression cloningextracellularflexibilityinnovationinsightknowledge basemacromoleculemedical schoolsmeetingsmembermetropolitannanomachinenovelnovel strategiespathogenprogramsprospectusesprotein complexprotein expressionprotein structurerepositoryrestraintscreeningstructural biologysuccesstechnology developmenttherapeutic developmenttumoruser-friendlyward
中文摘要
NYSGRC在高通量结构测定以及发现和实施基础设施以提高结构生物学研究的速度,准确性,成功率和可负担性方面拥有10年的良好记录。展望未来,NYSGRC将重组,以满足与PSI相关的新的和多样化的挑战:生物学网络。除了依赖传统的高通量细菌表达平台外,NYSGRC还将开发和实施尖端实验和计算技术,以研究作为PSI:生物学焦点的生物学重要分子。这些靶点可能包括多结构域真核蛋白、多组分组装体和分泌蛋白,这些蛋白包含复杂的多细胞生物学并直接促进人类健康和疾病。除了为高通量结构生物学伙伴关系提供服务外,该基础设施还将支持我们的生物主题,该主题侧重于主要细菌,原生动物和真菌病原体的分泌机制和分泌效应蛋白。这些目标是专门选择的,以提供新的见解,这些病原体已经演变为免疫逃避和调节宿主信号传导途径的机制。这些过程依赖于复杂的纳米机器,具有细胞质,膜相关和细胞外成分,需要混合计算和实验方法来定义它们的组织,结构和功能。最后,我们的综合实验和计算工作已经确定了新的机会,显着和经济地提高序列/结构的覆盖范围。
PSI的出现:生物学正在推动NYSGRC的进化变化过程,该过程已经增强了其出色的高通量结构测定管道。我们在传统细菌表达方面的优势,再加上真核表达和重折叠的新方法,以及我们在杂交方法方面的成熟专业知识,使我们能够独特地支持PSI的努力:生物学。
英文摘要
The NYSGRC has a 10-year proven track record in high-throughput structure determination as well as in discovering and implementing infrastructure to increase the speed, accuracy, success rate and affordability of structural biology studies. Moving forward the NYSGRC will reorganize to meet the new and diverse challenges associated with the PSI:Biology Network. In addition to reliance on traditional high-throughput bacterial expression platforms, the NYSGRC will develop and implement cutting-edge experimental and computational technologies to examine the biologically important molecules that are the focus of PSI:Biology. These targets are likely to include multidomain eukaryotic proteins, multi-component assemblies, and secreted proteins that underlay complex multi-cellular biology and directly contribute to human health and disease. In addition to servicing the High-Throughput-Enabled Structural Biology Partnerships, this infrastructure will support our Biological Theme that focuses on the secretion machinery and secreted effector proteins from major bacterial, protozoan and fungal pathogens. These targets were specifically selected to provide new insights into the mechanisms that these pathogens have evolved for immune evasion and modulation of host signaling pathways. These processes rely on intricate nano-machines, with cytoplasmic, membrane-associated and extracellular components, that require hybrid computational and experimental approaches to define their organization, structure and function. Finally, our integrated experimental and computational efforts have identified new opportunities to significantly and economically enhance sequence/structure coverage.
The advent of PSI:Biology is driving a process of evolutionary change for the NYSGRC that has already enhanced its outstanding high-throughput structure determination pipeline. Our strengths in traditional bacterial expression, coupled with novel approaches to eukaryotic expression and refolding, as well as our established expertise in hybrid methods, positions us to uniquely support the efforts of PSI:Biology.
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