National Center for Dynamic Interactome Research

国家动态相互作用组研究中心

• 批准号: 10401758
• 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 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10401758
• 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; 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; Seeds; Services; Signal Transduction; Systems Biology; Technology; Testing; Time; Training; Viral Cancer; Virus Diseases; base; 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

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.

项目概要 总体而言：国家动态相互作用组研究中心。 生命的涌现特性需要大分子（两大类）的动态相互作用。 它们是蛋白质和核酸。这些相互作用形成大分子机器和动态联络 塑造细胞、传递信息并控制细胞行为以及分子的致病性改变 相互作用网络（相互作用组）是疾病的基础。我们对生物系统的理解和调节， 以及它们的病理学，因此依赖于阐明和解释这些相互作用及其病理的能力 动力学。对于核酸来说，最近的进展导致了基因组数据的爆炸式增长。然而，蛋白质是 它们的丰富性和特性令人难以置信的多样化，使它们在动态任务中具有高度的通用性， 但同时又异常难以分析。正是由于这些原因，交互组学革命仍然 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 NCDIR 的目标是协同开拓新的和改进的方法，整合这些技术 转变为一种根本上独特的“管道”方法，以满足生物医学界的迫切需求 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。 我们的管道方法首先是开发纯化和保存技术，具有高保真度，各种 围绕任何选定的大分子的相互作用子的分层排列的定义形式。我们然后 为动态复合体提供全面、高度定量、详细的时间和结构数据。这样的 数据用于生成具有预测性、可测试性、可操作性和指导性的结构和机械模型 实验集中于那些信息最丰富的实验。这些模型旨在为生物医学界提供 具有基于合理目标的未来实验、功能表征甚至表征的手段 干涉。这些方法将通过一组选定的驾驶生物技术进行开发、完善和测试。 可以随时进入和退出我们的管道的项目和合作，并且呈现特定的 技术挑战。 NCDIR 设计的关键是有效的培训和传播计划 这满足了生物医学界的迫切需求。