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Agilent Complete 2D-LC-QTOF System

安捷伦完整的 2D-LC-QTOF 系统

基本信息

批准号：
10797808
负责人：
Ying Ge
金额：
$ 19.99万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-25 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10797808
关键词：
Address Antibodies Biological Assay Biological Markers Blood Cardiac Cardiovascular Diseases Cells Chemistry Code Collaborations Complex Computer software Diabetes Mellitus Diagnosis Disease Disease Progression Drug Targeting Electronics Equipment Extracellular Matrix Face Foundations Funding G Protein-Coupled Receptor Signaling G-Protein-Coupled Receptors Genetic Variation Genomics Heart Diseases Magnetic nanoparticles Mainstreaming Malignant Neoplasms Mass Spectrum Analysis Membrane Methods Molecular Nanotechnology Organic Chemistry Play Post-Translational Protein Processing Productivity Proteins Proteome Proteomics Publications Request for Proposals Research Role Solubility Structure Structure-Activity Relationship Surface System Technology Tissues Troponin I Variant biological systems design diagnostic assay empowerment human disease individual variation innovation insight interdisciplinary approach new therapeutic target novel novel strategies precision medicine success surfactant tool

项目摘要

Summary In the post-genomics era, a comprehensive analysis of “proteoforms” that arise from genetic variations and post-translational modifications (PTMs) is essential for understanding biological systems at a functional level and for dissecting complex molecular systems with consideration of individual variability for precision medicine. Top- down mass spectrometry (MS)-based proteomics that analyzes intact proteins is the most powerful method to comprehensively characterize proteoforms to decipher the PTM codes together with sequence variations. Although significant strides have been made recently in both MS hardware and software to advance top-down MS closer to the mainstream, top-down proteomics still faces major challenges. In particular, the proteome is extremely complex and has a high dynamic range in addition to the low solubility of many proteins, making it highly challenging for high-throughput proteomic study. Building on the success in the last funding period, in this multiple-PI renewal application, we will continue to develop innovative strategies empowered by nanotechnology and materials/organic chemistry to further address the challenges in top-down proteomics. The specific objectives of this proposal are: 1) To address the protein solubility challenge, we will develop a novel strategy enabled by a photocleavable surfactant for extracellular matrix (ECM) proteomics; and design, synthesize, and evaluate a novel class of photocleavable nonionic surfactants that can retain the native structures of proteins for native MS-based top-down proteomics. 2) To address the high dynamic range challenge, we will develop novel surface functionalized magnetic nanoparticles (NPs) to mimic antibodies for capturing and enriching low abundance proteins, such as cardiac troponin I (cTnI, a gold-standard biomarker for heart diseases) from tissues/blood and G-protein coupled receptors (GPCRs, a major class of drug targets) from cells/tissues, for downstream comprehensive analysis of all proteoforms by top-down proteomics. Our highly interdisciplinary approach integrates materials chemistry/nanotechnology with top-down MS-based proteomics, and is based on an existing productive collaboration between two PIs that has led to significant progress and publications from the past funding period. Success in our proposed research will provide innovative tools to enable top-down proteomics of poorly soluble and low abundance proteins, which will lay important technological foundation for understanding the critical role that ECM plays in disease progression in cancer and cardiac diseases, defining the structure-function relationship of native membrane complexes, developing a comprehensive cTnI assay for the diagnosis of cardiac diseases with high accuracy, and understanding the important roles of GPCR signaling during the onset of numerous human diseases including cancer, diabetes, and cardiovascular diseases.

总结

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Comprehensive characterization of monoclonal antibody by Fourier transform ion cyclotron resonance mass spectrometry.

DOI：
10.1080/19420862.2018.1525253
发表时间：
2019-01
期刊：
mAbs
影响因子：
5.3
作者：
Jin Y;Lin Z;Xu Q;Fu C;Zhang Z;Zhang Q;Pritts WA;Ge Y
通讯作者：
Ge Y

PP2A-B' holoenzyme substrate recognition, regulation and role in cytokinesis.

DOI：
10.1038/celldisc.2017.27
发表时间：
2017
期刊：
Cell discovery
影响因子：
33.5
作者：
Wu CG;Chen H;Guo F;Yadav VK;Mcilwain SJ;Rowse M;Choudhary A;Lin Z;Li Y;Gu T;Zheng A;Xu Q;Lee W;Resch E;Johnson B;Day J;Ge Y;Ong IM;Burkard ME;Ivarsson Y;Xing Y
通讯作者：
Xing Y

A Family of Photolabile Nitroveratryl-Based Surfactants That Self-Assemble into Photodegradable Supramolecular Structures.