Equipment Supplement for the National Center for Dynamic Interactome Research

项目摘要 国家动态相互作用研究中心（National Center for Dynamic Interactome Research） 生命的涌现特性需要大分子的动态相互作用，这两大类 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 形成细胞，传递信息和控制细胞行为，以及分子 相互作用网络（interactomes）是疾病的基础。我们对生物系统的理解和调节， 以及他们的病理学，因此依赖于阐明和解释这些相互作用及其相互作用的能力。 动力学对于核酸，最近的进展导致了基因组数据的爆炸。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，使它们在动态任务中具有高度的通用性， 但同时又非常难以分析。正是由于这些原因， 远远落后于基因组革命。 美国国家动态相互作用研究中心（NCENTRAL）将细胞生物学实验室与马萨诸塞州的 光谱实验室、系统生物学实验室和计算结构生物学实验室。的 美国国家科学技术委员会的目标是协同开拓新的和改进的方法，将这些技术集成起来 成为一个基本上独特的“管道”的方法，以解决生物医学界的迫切需要， 可以快速、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净化和保存技术，具有高保真度， 围绕任何选定的大分子的相互作用物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。等 数据用于生成结构和机制模型，这些模型具有预测性、可测试性、可操作性和指导性 实验集中在那些信息量最大的。这些模型旨在为生物医学界提供 与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一套选定的生物驱动技术来开发、改进和测试。 项目和合作，可以进入和退出我们的管道在任何时候，并提出具体的 技术挑战。设计国家信息和通信技术中心的关键是一个有效的培训和传播方案 这符合生物医学界的迫切需要。

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.