Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules
Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules
批准号:
10543449
负责人:
Jennifer S. Brodbelt
金额:
$64.61万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-01-01 至 2025-12-31
关键词:
Antibiotic ResistanceAreaBindingBiologicalBiomedical ResearchC-terminalCapillary ElectrophoresisCellular MembraneChemicalsCollaborationsComplexDiseaseGenetic TranscriptionGoalsHybridsIndividualLigandsLipidsMass Spectrum AnalysisMembrane ProteinsMethodsMicrobiologyModificationMolecularMolecular BiologyNucleic AcidsPatternPhosphorylationPost-Translational Protein ProcessingProteinsRNA Polymerase IIResearchStructureTechnologydesignfrontierfunctional outcomesinnovationinsightmacromolecular assemblynovel therapeuticsoxidationpathogenic bacteriaprogramsprotein complexprotein functiontandem mass spectrometryultraviolet
中文摘要
抽象的。了解脂类、蛋白质甚至更大的大分子组件的功能
依赖于破译单个分子的复杂结构,以及解密这些分子是如何
分子之间相互作用,通常是通过非共价相互作用网络。为了推进对……的澄清
生物分子组织和功能结果,需要新的方法来推动
结构洞察力,以更高的灵敏度提供更详细的整体化学信息。关键人物
结构/功能之间的相互作用在许多生物动机的问题上得到了证明,范围
从了解病原菌产生抗生素耐药性的方式到设计新的
选择性结合和抑制蛋白质靶标功能的药物。持续不断的需求甚至更大
化学洞察力促使我的团队努力开发创新的质谱学方法
以前所未有的细节描述生物分子结构,特别是脂类和蛋白质
这些都是这份提案中的特色。我的研究计划的首要目标是开发国家
最先进的串联质谱学技术,特别是突出紫外光解离
(UVPD)和MS/MS混合方法,用于脂类、蛋白质和蛋白质复合体的结构鉴定。
这些新方法将展示在三个领域解决具有挑战性的问题。(1)脂类:(I)
病原菌的脂类及其抗生素耐药性特征,以及(Ii)结构
过程中发生的不饱和、氧化和其他脂质修饰的特征
细胞膜的重塑。(2)蛋白质复合体:(I)蛋白质-配体的表征
复合体、膜蛋白复合体、蛋白质/核酸复合体和大分子
以及(Ii)先进的毛细管电泳法用于天然分离和探索
互动组。(3)翻译后修饰:重点破译其磷酸化模式
核糖核酸聚合酶II的C-末端结构域,调节转录。这些影响很大的问题
通过与微生物学和分子生物学团体的大量合作得到支持
认识到前沿质谱学策略对提升生物医学研究的价值。
英文摘要
Abstract. Understanding the functions of lipids, proteins and even larger macromolecular assemblies
depends on deciphering complex structures of individual molecules as well as decrypting how those
molecules interact, often via networks of non-covalent interactions. In order to advance the elucidation of
biomolecular organization and functional outcomes, new methods are needed to push the limits of
structural insight, providing more detailed holistic chemical information with greater sensitivity. The critical
interplay between structure/function is evidenced in numerous biologically-motivated problems, ranging
from understanding the ways that pathogenic bacteria develop antibiotic resistance to the design of new
drugs that selectively bind and inhibit the functions of protein targets. The ongoing need for even greater
chemical insight has motivated my group’s effort to develop innovative mass spectrometry methods to
characterize structures of biological molecules in unprecedented detail, especially lipids and proteins
which are featured in this proposal. The overarching goal of my research program is to develop state-of-
the-art tandem mass spectrometry technologies, particularly highlighting ultraviolet photodissociation
(UVPD) and hybrid MS/MS methods, for structural elucidation of lipids, proteins, and protein complexes.
These new methods will be showcased for solving challenging problems in three areas. (1) Lipids: (i)
profiling lipids of pathogenic bacteria and their signatures of antibiotic resistance, and (ii) structural
characterization of unsaturations, oxidations and other modifications of lipids that occur during
remodeling of cellular membranes. (2) Protein complexes: (i) characterization of protein-ligand
complexes, membrane protein complexes, protein/nucleic acid complexes, and macromolecular
assemblies, and (ii) advancing capillary electrophoresis for native separations and exploration of the
interactome. (3) Post-translational modifications: focusing on decoding the phosphorylation patterns of
the C-terminal domain of RNA polymerase II which regulates transcription. These high impact problems
are supported via numerous collaborations with microbiology and molecular biology groups who
recognize the value of frontier mass spectrometry strategies for elevating biomedical research.
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Problem-to-Product Team Entrepreneurship and Active Mentoring (P2P-TEAM) Graduate Training Program
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批准号:10418608
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项目类别:
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资助金额:$17.03万
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财政年份:2021
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负责人:Jennifer S. Brodbelt
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依托单位:
Problem-to-Product Team Entrepreneurship and Active Mentoring (P2P-TEAM) Graduate Training Program
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批准号:10620850
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项目类别:
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资助金额:$17.44万
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财政年份:2021
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负责人:Jennifer S. Brodbelt
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依托单位:
Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules
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批准号:10320024
-
项目类别:
-
资助金额:$64.61万
-
财政年份:2021
-
负责人:Jennifer S. Brodbelt
-
依托单位:
Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules
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批准号:10389836
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项目类别:
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资助金额:$10.04万
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财政年份:2021
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负责人:Jennifer S. Brodbelt
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依托单位:
Problem-to-Product Team Entrepreneurship and Active Mentoring (P2P-TEAM) Graduate Training Program
-
批准号:10089703
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项目类别:
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资助金额:$7.86万
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财政年份:2021
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负责人:Jennifer S. Brodbelt
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依托单位:
Ultraviolet Photodissociation Mass Spectrometry for Characterization of Biological Molecules
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批准号:10797256
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项目类别:
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资助金额:$16.0万
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财政年份:2021
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负责人:Jennifer S. Brodbelt
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依托单位:
Interpretation of the phosphorylation code of RNA polymerase II during eukaryotic transcription
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批准号:9751900
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项目类别:
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资助金额:$34.7万
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财政年份:2018
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负责人:Jennifer S. Brodbelt
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依托单位:
Interpretation of the phosphorylation code of RNA polymerase II during eukaryotic transcription
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批准号:10158496
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项目类别:
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资助金额:$34.7万
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财政年份:2018
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负责人:Jennifer S. Brodbelt
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依托单位:
UVPD Mass Spectrometry of Protein Complexes
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批准号:9217240
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项目类别:
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资助金额:$28.47万
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财政年份:2017
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负责人:Jennifer S. Brodbelt
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依托单位:
UVPD Mass Spectrometry of Protein Complexes
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批准号:9539104
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项目类别:
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资助金额:$3.73万
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财政年份:2017
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负责人:Jennifer S. Brodbelt
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依托单位:
Cracking the Ubiquitination Code by Top Down Mass Spectrometry
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批准号:8959461
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项目类别:
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资助金额:$18.94万
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财政年份:2015
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负责人:Jennifer S. Brodbelt
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依托单位:
Mapping the C Terminal Domain of RNA Polymerase II by UVPD Mass Spectrometry
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批准号:8676088
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项目类别:
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资助金额:$21.7万
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财政年份:2014
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负责人:Jennifer S. Brodbelt
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依托单位:
Mapping the C Terminal Domain of RNA Polymerase II by UVPD Mass Spectrometry
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批准号:8806559
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项目类别:
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资助金额:$18.77万
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财政年份:2014
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负责人:Jennifer S. Brodbelt
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依托单位:
IRACDA Postdoctoral Program: Collaborative Opportunities for Research Educators
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批准号:8697068
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项目类别:
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资助金额:$43.59万
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财政年份:2013
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负责人:Jennifer S. Brodbelt
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依托单位:
IRACDA Postdoctoral Program: Collaborative Opportunities for Research Educators
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批准号:9086376
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项目类别:
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资助金额:$62.11万
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财政年份:2013
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负责人:Jennifer S. Brodbelt
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依托单位:
IRACDA Postdoctoral Program: Collaborative Opportunities for Research Educators
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批准号:8550189
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项目类别:
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资助金额:$22.83万
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财政年份:2013
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负责人:Jennifer S. Brodbelt
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依托单位:
IRACDA Postdoctoral Program: Collaborative Opportunities for Research Educators
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批准号:8901205
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项目类别:
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资助金额:$62.26万
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财政年份:2013
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负责人:Jennifer S. Brodbelt
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依托单位:
IRACDA Postdoctoral Program: Collaborative Opportunities for Research Educators
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批准号:9297315
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项目类别:
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资助金额:$33.42万
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财政年份:2013
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负责人:Jennifer S. Brodbelt
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依托单位:
Mass Spectrometric Characterization of Lipopolysaccharides
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批准号:8547083
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项目类别:
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资助金额:$26.85万
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财政年份:2012
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负责人:Jennifer S. Brodbelt
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依托单位:
Mass Spectrometric Characterization of Lipopolysaccharides
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批准号:8438821
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项目类别:
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资助金额:$30.81万
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财政年份:2012
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负责人:Jennifer S. Brodbelt
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