NMR Technologies for Integrating Structure, Function and Disease
整合结构、功能和疾病的 NMR 技术
基本信息
- 批准号:10573321
- 负责人:
- 金额:$ 113.97万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-01-02 至 2025-12-31
- 项目状态:未结题
- 来源:
- 关键词:3D PrintAccelerationAddressAlgorithmsAmyloidAmyloid FibrilsAntifungal AgentsAreaArecaAutomatic Data ProcessingAutomationAutomobile DrivingBenchmarkingBindingBiologicalBiologyBiomedical ResearchBiomolecular Nuclear Magnetic ResonanceBiotechnologyBlood coagulationCalibrationChadChemicalsChronologyCollaborationsCommunitiesComplexComputer softwareCosts and BenefitsCustomDataData AnalysesData CollectionDedicationsDevelopmentDiameterDiseaseEducational workshopEnsureEnvironmentEnzymesFeedbackFoundationsFree EnergyFundingFutureG-Protein-Coupled ReceptorsGoalsGrantHealthHuman ResourcesIllinoisIn VitroInstructionInvestmentsIonic StrengthsKineticsKnowledgeLearningLewy BodiesLigandsLinuxMagicMeasurementMediationMedicineMembraneMembrane ProteinsMethodsMichiganMicroscopicModelingModernizationMultienzyme ComplexesNMR SpectroscopyNeurodegenerative DisordersNucleic AcidsOperating SystemOutcomePathogenicityPathologyPharmaceutical PreparationsPhysiologicalPreparationProceduresProductivityProteinsProtocols documentationPublishingReportingReproducibilityResearch InfrastructureResolutionResourcesRestRunningSamplingScienceServicesSolidSpecificitySpeedSterolsStructureSurfaceSystemTechnologyTechnology TransferTestingThermodynamicsTimeTissue SampleTranslatingValidationbasecommunity engagementcomputerized data processingcostdata acquisitiondata qualitydesignexperimental studyflexibilitygraphical user interfaceimprovedinnovationionization constantmeetingsnew technologyprogramsprotein foldingquantum chemistryrecruitsenior facultysmall moleculesolid statesolid state nuclear magnetic resonancetechnology developmenttoolweb site
项目摘要
INTRODUCTION TO REVISED APPLICATION
The A0 grant was submitted in May 2019, before Prof. Alexander Barnes moved to ETH-Zurich and before Prof.
Chad Rienstra was recruited to UW-Madison. Now Rienstra is officially a Full Professor at UW-Madison, after
having negotiated major investments in the solid-state NMR (SSNMR) program at NMRFAM (new and/or moving
from Illinois) including three shielded 600 MHz magnets, one 750 MHz wide bore magnet, four spectrometers,
several custom-designed magic-angle spinning (MAS) probes at 600-750 MHz, and upgrades to the 900 MHz
spectrometer, which immediately have had an impact on data collection for DBP6 in late 2019 and for other
experiments in progress during early 2020.
Furthermore, the National Science Foundation Mid-Scale Research Infrastructure-2 proposal on "Network for
Advanced NMR", which was submitted by UW-Madison PIs (Rienstra and Henzler-Wildman) in collaboration
with Jeff Hoch at UConn Health and Art Edison at U. Georgia, is in late stages of negotiation and review with
NSF. If funded, this grant would bring a 1.1 GHz dedicated SSNMR spectrometer to NMRFAM in ~2022-23.
These developments have motivated several changes to this A1 application which more explicitly emphasizes
the SSNMR program at NMRFAM:
(1) Rienstra is now contact PI and Henzler-Wildman co-PI.
(2) TR&D1 now includes sub-aims targeting development of micro-rotor packing and sample manipulation
tools to leverage recent breakthroughs in ultra-fast MAS (>100 kHz) at <1 mm rotor diameters; this
broadens the scope and impact of TR&D 1. Baselines and benchmarks for NMR under gradients are also
more clearly described and proof-of-principle experiments are in place.
(3) TR&D2 now addresses critical bottlenecks in SSNMR data collection, emphasizing:
(a) automation for parameter optimization and spectrometer configuration;
(b) new narrow bore magic-angle spinning probe designs at 600-900 MHz (that will be applicable at 1.1
GHz and higher in the future); and
(c) real-time feedback interaction with data processing (TR&D3).
(4) TR&D3 now leverages NMRFAM software products and continuing technology development for solid-
state NMR, including assignment, structure determination, refinement and validation tools, and it is more
clearly integrated with the rest of the proposal.
(5) DBPs 5, 6 and 7 have been changed to include well-developed and impactful collaborations between
Rienstra and Paul Kotzbauer (Wash. U. Medicine, Lewy bodies and synucleiopathies), Marty Burke (U.
Illinois, antifungal drugs), and James Morrissey (U. Michigan, blood coagulation).
Overall the proposal is now organized in (we think) a more logical/chronological manner, with TR&D1
emphasizing samples, TR&D2 the spectrometer and probes, and TR&D3 the software and analysis procedures.
The proposal body further explains how these developments greatly augment the cost-benefit ratio for the project
and integrate with the current user program and the long-term vision of NMRFAM.
The revisions also address the overarching concerns of reviewers of the A0 application including "narrow
scope/modest innovation in TR&D1"; "weak integration of TR&D3"; cost-benefit ratio; preliminary data; solution
vs. solids emphasis of TR&D3; innovation; context (addressing competing ideas and precedents); and specificity
of outcomes. Finally, we have clarified the premise and approach with respect to asymmetry in membrane
proteins.
经修订的申请简介
A0补助金于2019年5月提交,在亚历山大巴恩斯教授搬到苏黎世联邦理工学院之前,
乍得Rienstra被招募到威斯康星大学麦迪逊分校。现在Rienstra正式成为威斯康星大学麦迪逊分校的正教授,
已经谈判了在固态核磁共振(SSNMR)计划在NMRFAM(新的和/或移动的主要投资
来自Illinois),包括三个屏蔽的600 MHz磁体,一个750 MHz宽孔磁体,四个光谱仪,
几个定制设计的600-750 MHz魔角旋转(MAS)探头,并升级到900 MHz
光谱仪,这立即对2019年底DBP 6和其他
2020年初进行中的实验。
此外,国家科学基金会中型研究基础设施-2提案“网络,
高级NMR”,由UW-Madison PI(Rienstra和Henzler-Wildman)合作提交
与康州大学健康中心的杰夫·霍克和美国大学的艺术爱迪生一起。格鲁吉亚正处于与
NSF。如果获得资助,这笔赠款将于2022-23年为NMRFAM带来一台1.1 GHz专用SSNMR光谱仪。
这些发展促使对A1应用程序进行了几项更改,
NMRFAM的SSNMR程序:
(1)Rienstra现在是PI和Henzler-Wildman的共同PI。
(2)TR&D1现在包括针对微型转子包装和样品操作开发的子目标
利用最近在转子直径<1 mm的超快MAS(>100 kHz)方面的突破的工具;
扩大了TR&D 1的范围和影响。还提供了梯度下NMR的基线和基准
更明确的描述和原理验证实验已经到位。
(3)TR&D2现在解决了SSNMR数据收集中的关键瓶颈,强调:
(a)参数优化和光谱仪配置的自动化;
(b)600-900 MHz的新窄孔魔角旋转探头设计(适用于1.1 MHz
GHz及未来更高);以及
(c)与数据处理的实时反馈交互(TR&D3)。
(4)TR&D3现在利用NMRFAM软件产品和持续的技术开发,
国家NMR,包括分配,结构测定,完善和验证工具,它是更多
与提案的其余部分完全融合。
(5)DBPs 5、6和7已更改,以包括以下方面之间发展良好且有影响力的合作:
Rienstra和Paul Kotzbauer(华盛顿州)联合医学,路易体和突触核病),马蒂伯克(美国。
伊利诺斯州,抗真菌药物)和詹姆斯莫里西(美国。Michigan,血液凝固)。
总的来说,现在的提案(我们认为)是以一种更符合逻辑/时间顺序的方式组织的,TR&D1
TR&D2侧重于样品,TR&D3侧重于软件和分析程序。
提案主体进一步解释了这些发展如何大大提高项目的成本效益比
并与当前的用户计划和NMRFAM的长期愿景相结合。
这些修订还解决了A0申请审查人员的首要问题,包括“狭窄”,
TR&D1的范围/适度创新”;“TR&D3的弱整合”;成本效益比;初步数据;解决方案
vs. TR&D3的重点;创新;背景(解决相互竞争的想法和先例);和特殊性
结果。最后,我们阐明了关于膜不对称性的前提和途径
proteins.
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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Katherine Anne Henzler-Wildman其他文献
Katherine Anne Henzler-Wildman的其他文献
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{{ truncateString('Katherine Anne Henzler-Wildman', 18)}}的其他基金
Expanding the Scope of NMR Sample Preparation
扩大 NMR 样品制备的范围
- 批准号:
10089600 - 财政年份:2021
- 资助金额:
$ 113.97万 - 项目类别:
Expanding the Scope of NMR Sample Preparation
扩大 NMR 样品制备的范围
- 批准号:
10573324 - 财政年份:2021
- 资助金额:
$ 113.97万 - 项目类别:
NMR Technologies for Integrating Structure, Function and Disease
整合结构、功能和疾病的 NMR 技术
- 批准号:
10089598 - 财政年份:2021
- 资助金额:
$ 113.97万 - 项目类别:
Molecular Mechanisms of Channels and Transporters
通道和转运蛋白的分子机制
- 批准号:
10608951 - 财政年份:2021
- 资助金额:
$ 113.97万 - 项目类别:
NMR Technologies for Integrating Structure, Function and Disease
整合结构、功能和疾病的 NMR 技术
- 批准号:
10323282 - 财政年份:2021
- 资助金额:
$ 113.97万 - 项目类别:
Molecular Mechanisms of Channels and Transporters
通道和转运蛋白的分子机制
- 批准号:
10204502 - 财政年份:2021
- 资助金额:
$ 113.97万 - 项目类别:
Expanding the Scope of NMR Sample Preparation
扩大 NMR 样品制备的范围
- 批准号:
10323284 - 财政年份:2021
- 资助金额:
$ 113.97万 - 项目类别:
Molecular Mechanisms of Channels and Transporters
通道和转运蛋白的分子机制
- 批准号:
10394922 - 财政年份:2021
- 资助金额:
$ 113.97万 - 项目类别:
CONFORMATIONAL DYNAMICS IN ION CHANNEL SELECTIVITY AND GATING
离子通道选择性和门控中的构象动力学
- 批准号:
8945932 - 财政年份:2015
- 资助金额:
$ 113.97万 - 项目类别:
CONFORMATIONAL DYNAMICS IN ION CHANNEL SELECTIVITY AND GATING
离子通道选择性和门控中的构象动力学
- 批准号:
9133430 - 财政年份:2015
- 资助金额:
$ 113.97万 - 项目类别:
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