National Center for Dynamic Interactome Research

国家动态相互作用组研究中心

• 批准号: 10621352
• 负责人: MICHAEL P ROUT
• 金额: $ 137.57万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10621352
• 关键词: Address; Adoption; Architecture; Area; Automobile Driving; Binding; Biological; Biological Process; Biology; Cell Nucleus; Cell Shape; Cell physiology; Cells; Cellular biology; Collaborations; Communities; Complex; Computer software; Couples; Data; Data Analyses; Development; Disease; Ensure; Explosion; Future; Genomics; Goals; Intervention; Laboratories; Life; Macromolecular Complexes; Mass Spectrum Analysis; Mediating; Medical Research; Methods; Microscope; Modeling; Molecular; Molecular Structure; Morphology; Noise; Nucleic Acids; Pathogenicity; Pathology; Pharmacologic Substance; Process; Property; Proteins; Reagent; Research; Research Personnel; Resolution; Resources; Route; Sampling; Services; Signal Transduction; Systems Biology; Technology; Testing; Time; Training; Viral Cancer; Virus Diseases; Visualization; biological systems; cell behavior; computerized tools; data modeling; design; diverse data; experimental study; genomic data; improved; insight; instrumentation; interest; macromolecule; new technology; predictive modeling; preservation; program dissemination; spatial relationship; stoichiometry; structural biology; technology research and development; tool; transmission process

PROJECT SUMMARY Overall: The National Center for Dynamic Interactome Research. The emergent properties of life require the dynamic interactions of macromolecules, the two major classes of which are proteins and nucleic acids. These interactions form macromolecular machines and dynamic liaisons that shape the cell, transmit information and control cellular behaviors, and pathogenic alterations in molecular interaction networks (interactomes) underlie disease. Our understanding and modulation of biological systems, as well as their pathologies, thus relies on the ability to elucidate and interpret these interactions and their dynamics. For nucleic acids, recent advances have led to an explosion of genomic data. However, proteins are incredibly diverse in their abundance and their properties, making them highly versatile for their dynamic tasks, but at the same time exceptionally difficult to analyze. It is for these reasons that the interactomic revolution still lags very far behind the genomic revolution. The National Center for Dynamic Interactome Research (NCDIR) couples cell biology laboratories, a mass spectrometry laboratory, a systems biology laboratory, and a computational structural biology laboratory. The goal of the NCDIR is to synergistically pioneer new and improved approaches, integrating these technologies into a fundamentally unique “pipeline” approach to address the urgent need of the biomedical community for technologies that can rapidly, reliably and routinely identify and characterize the dynamic cellular interactome. Our pipeline approach begins by developing technologies for purifying and preserving, with high fidelity, various defined forms of the hierarchical arrangement of interactors surrounding any chosen macromolecule. We then provide comprehensive, highly quantitative, detailed temporal and structural data for dynamic complexes. Such data is used to generate structural and mechanistic models that are predictive, testable, actionable, and guide experiments to focus on those that are most informative. The models aim to provide the biomedical community with the means for rational target-based future experimentation, functional characterizations and even intervention. These approaches will be developed, refined and beta-tested via a selected set of Driving Biological Projects and Collaborations that can enter and exit our pipeline at any point, and which present specific technological challenges. Critical to the design of the NCDIR is an effective training and dissemination program that is responsive to the urgent needs of the biomedical community.

项目总结 总体情况：国家动态交互基因组研究中心。 生命的涌现特性需要大分子的动态相互作用，大分子是生命的两大类 它们是蛋白质和核酸。这些相互作用形成了大分子机器和动态联系 它们塑造细胞，传递信息，控制细胞行为，以及分子中的致病变化 相互作用网络(相互作用)是疾病的基础。我们对生物系统的理解和调节， 以及它们的病理，因此依赖于阐明和解释这些相互作用和它们的 动力学。对于核酸，最近的进展导致了基因组数据的爆炸性增长。然而，蛋白质是 它们的丰富性和特性令人难以置信地多样化，使它们对于动态任务具有高度的多功能性， 但与此同时，分析也格外困难。正是由于这些原因，截肢革命仍在继续 远远落后于基因组革命。 国家动态相互作用组研究中心(NCDIR)联合了一大批细胞生物学实验室 光谱实验室、系统生物学实验室和计算结构生物学实验室。这个 NCDIR的目标是协同开创新的和改进的方法，整合这些技术 成为一种从根本上独特的“管道”方法，以满足生物医学界对 能够快速、可靠和常规地识别和表征动态细胞相互作用组的技术。 我们的流水线方法首先开发纯化和保存技术，高保真地、各种 围绕任何所选大分子的相互作用的分级排列的定义形式。然后我们 为动态复合体提供全面、高度定量、详细的时间和结构数据。是这样的 数据用于生成可预测、可测试、可操作和可指导的结构和机械模型 把重点放在那些信息量最大的实验上。这些模型旨在为生物医学社区提供 以合理的目标为基础的未来实验，功能表征，甚至 干预。这些方法将通过选定的一组驾驶生物进行开发、改进和Beta测试 可以随时进入和退出我们渠道的项目和协作，以及呈现特定 技术挑战。对NCDIR的设计至关重要的是有效的培训和传播方案 这是对生物医学界的迫切需求的回应。

项目成果

Lineage-specific proteins essential for endocytosis in trypanosomes.

• DOI: 10.1242/jcs.191478
• 发表时间: 2017-04-15
• 期刊: Journal of cell science
• 影响因子: 4
• 作者: Manna PT;Obado SO;Boehm C;Gadelha C;Sali A;Chait BT;Rout MP;Field MC
• 通讯作者: Field MC

Dengue activates mTORC2 signaling to counteract apoptosis and maximize viral replication.

• DOI: 10.3389/fcimb.2022.979996
• 发表时间: 2022
• 期刊: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
• 影响因子: 5.7
• 作者: Carter, Christoph C.;Mast, Fred D.;Olivier, Jean Paul;Bourgeois, Natasha M.;Kaushansky, Alexis;Aitchison, John D.
• 通讯作者: Aitchison, John D.

Optimized Affinity Capture of Yeast Protein Complexes.

• DOI: 10.1101/pdb.prot087932
• 发表时间: 2016-07
• 期刊: Cold Spring Harbor protocols
• 作者: J. LaCava;Javier Fernandez-Martinez;Zhanna Hakhverdyan;M. Rout

Analysis of Multivalent IDP Interactions: Stoichiometry, Affinity, and Local Concentration Effect Measurements.

• DOI: 10.1007/978-1-0716-0524-0_23
• 发表时间: 2020
• 期刊: Methods in molecular biology
• 作者: Samuel Sparks;R. Hayama;M. Rout;D. Cowburn

A general method for quantitative fractionation of mammalian cells.

• DOI: 10.1083/jcb.202209062
• 发表时间: 2023-06-05
• 期刊: JOURNAL OF CELL BIOLOGY
• 影响因子: 7.8
• 作者: Udi, Yael;Zhang, Wenzhu;Stein, Milana E. E.;Ricardo-Lax, Inna;Pasolli, Hilda A. A.;Chait, Brian T. T.;Rout, Michael P. P.
• 通讯作者: Rout, Michael P. P.