National Center for Quantitative Biology of Complex Systems

项目总结 用于询问基因表达的基因组技术的出现已经不可逆转地改变了 科学家们研究生物问题。更具体地说，大规模基因表达测序 技术使我们能够以前所未有的速度收集对生物学和疾病发病机制的见解。 然而，RNA水平只是高度复杂的生物学谜题的一部分：基因是 细胞调节过程，而代谢物往往是最终产品和最终的生物效应器 分子。有许多层的表达后调控，微调路径中的生物系统 从基因到蛋白质再到代谢物。认识蛋白质及其翻译后的核心作用 在这一过程中，国家复杂系统数量生物学中心 为这些分子提供大规模的定量数据。我们的生物技术研究资源 旨在加快蛋白质组、代谢组和脂组定量的速度、深度和准确性。受驱动 根据生物医学研究人员的需求，我们的使命是开发能够提供快速访问 最全面、最准确的生物状态记者。具体地说，我们将(1)扩展并最终 使我们能够进行全面的生物分子表征的工作达到高潮；(2)发展和总结我们的工作 实现高度多元化的蛋白质组量化和(3)在小说开发方面的开创性进展 用于全集成多组体分析的色谱和质谱学平台。 我们将在几个高影响力的推动生物医学研究项目的背景下开发这些技术 这需要新的技术进步才能取得成功，这可以作为技术试验台。这些 推动项目包括两个中心主题。第一，回应生物医学研究人员的要求 探索新兴而又鲜为人知的生物分子及其PTM的作用，我们将以项目为目标 关注新的代谢物衍生的翻译后修饰。第二，我们已经开始认识到 除了蛋白质测量之外，我们的合作者还需要新的技术来识别和量化 代谢物和脂质，以充分了解它们感兴趣的生物系统，我们将与许多 允许我们测试和改进大规模系统和多组学分析的技术的项目，以 探索生理学和新陈代谢。最后，我们提出了一个多方面的方法来传播、培训和 协作，最终目标是确保我们的技术产生持续的影响。我们所有的技术 都是可持续的，我们已经建立了系统和非正式的机制来交付我们的 将知识和创新带给科学界。

PROJECT SUMMARY The advent of genome technologies for interrogating gene expression has irreversibly changed the scale at which scientists investigate biological problems. More specifically, large-scale gene expression sequencing technologies have allowed us to glean insights into biology and disease pathogenesis at unprecedented pace. However, RNA levels are only one piece of a highly complex biological puzzle: genes are the starting point of the cellular regulatory process, while metabolites are often the end products and the ultimate biological effector molecules. There are many layers of regulation post-expression that fine-tune the biological system in the path from gene to protein to metabolite. Recognizing the central role of proteins and their post-translational modifications (PTMs) in this process, the National Center for Quantitative Biology of Complex Systems was founded to provide large-scale quantitative data for these molecules. Our Biotechnology Research Resource aims to accelerate the pace, depth, and accuracy of quantifying the proteome, metabolome, and lipidome. Driven by the needs of biomedical researchers, our mission is to develop technologies that provide rapid access to the most comprehensive and accurate reporters of the biological state. Specifically we will (1) extend and ultimately culminate our work to enable comprehensive biomolecule characterization; (2) develop and conclude our work enabling highly multiplexed proteome quantification and (3) break ground on the development of the novel chromatographic and mass spectrometry platform for wholly integrated multi-omic analysis. We shall develop these technologies in the context of several high impact driving biomedical research projects that require the new technological advancements for success and that can serve as technology testbeds. These driving projects comprise two central themes. First, responding to the demands of biomedical researchers to explore the roles of emergent and yet poorly understood biomolecules and their PTMs, we will target projects concerned with new, metabolite-derived post-translational modifications. Second, we have come to appreciate that in addition to protein measurements our collaborators require new technologies to identify and quantify metabolites and lipids to fully understand their biological systems of interest and we will work with a host of projects that allow us to test and refine technologies for the large-scale systems and multi-omics analyses to explore physiology and metabolism. Finally, we propose a multi-faceted approach to dissemination, training, and collaboration, with the ultimate aim of ensuring the sustained impact of our technology. All of our technologies are designed to be sustainable, and we have created both systematic and informal mechanisms to deliver our knowledge and innovations to the scientific community.