National Center for Dynamic Interactome Research

国家动态相互作用组研究中心

• 批准号: 9268522
• 负责人: MICHAEL P ROUT
• 金额: $ 214.36万
• 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 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9268522
• 关键词: Address; Area; Automobile Driving; Behavior; Binding; Biological; Biological Process; Cell Shape; Cell physiology; Cells; Cellular biology; Collaborations; Communities; Complex; Couples; Data; Development; Disease; Drug Design; Explosion; Genomics; Goals; Laboratories; Life; Mass Spectrum Analysis; Mediating; Medical Research; Modeling; Molecular; Nucleic Acids; Pathogenicity; Pathology; Pharmacologic Substance; Property; Proteins; Research; Research Personnel; Resources; Systems Biology; Technology; Testing; Time; Training; Viral Cancer; Virus Diseases; base; biological systems; design; experimental study; genomic data; improved; insight; macromolecule; novel; predictive modeling; program dissemination; public health relevance; structural biology; therapy design; tool

DESCRIPTION (provided by applicant): 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 ags very far behind the genomic revolution. The proposed National Center for Dynamic Interactome Research (NCDIR) couples cell biology laboratories, an established mass spectrometry resource, a systems biology resource, and a computational structural biology center. The goal of the NCDIR is to synergistically pioneer new and improved approaches, integrating these technologies into a fundamentally novel "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. We will begin by developing technologies for purifying and preserving, with high fidelity, various defined forms of the hierarchical arrangement of interactors surrounding any chosen macromolecule. We will then provide comprehensive, highly quantitative, detailed temporal and structural data for dynamic complexes. Such data will be 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 intervention and drug design strategies. 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.

描述（由申请人提供）：生命的紧急特性需要大分子的动态相互作用，这两个主要类别是蛋白质和核酸。这些相互作用构成了塑造细胞，传输信息和控制细胞行为的大分子机器和动态联络，以及分子相互作用网络（相互作用）的致病性改变。因此，我们对生物系统及其病理的理解和调节依赖于阐明和解释这些相互作用及其动态的能力。对于核酸，最近的进步导致基因组数据的爆炸爆炸。但是，蛋白质的丰富性和特性非常多样，使其在动态任务方面具有高度的用途，但同时也很难分析。正是由于这些原因，相互作用的革命仍然远远落后于基因组革命。拟议的国家动态互动研究中心（NCDIR）夫妇生物学实验室，已建立的质谱资源，系统生物学资源和计算结构生物学中心。 NCDIR的目的是协同开创性的新方法和改进的方法，将这些技术整合到一种根本上新颖的“管道”方法中，以解决生物医学群落的迫切需求，以迅速，可靠，可靠，常规地识别和表征动态蜂窝相互作用。我们将首先开发用于净化和保存的技术，并以高忠诚度，各种定义的形式的层次结构排列形式围绕任何选择的大分子。然后，我们将为动态复合物提供全面，高度定量的时间和结构数据。此类数据将用于生成具有预测性，可检验，可操作和指导实验的结构和机械模型，以专注于最有用的内容。该模型旨在为生物医学界提供基于目标的干预和药物设计策略的手段。这些方法将通过一组选定的驾驶生物项目和协作进行开发，完善和测试，这些项目和协作可以在任何时候输入和退出我们的管道，并提出具体的技术挑战。对NCDIR的设计至关重要的是一项有效的培训和传播计划，可满足生物医学界的紧急需求。