National Center for Quantitative Biology of Complex Systems

国家复杂系统定量生物学中心

• 批准号: 10089073
• 负责人: JOSHUA J COON
• 金额: $ 28.19万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-05 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10089073
• 关键词: Acylation; Affect; Animal Model; Area; Automobile Driving; Bioenergetics; Biological; Biology; Biotechnology; Cell physiology; Cells; Collaborations; Communities; Complex; Coupled; Development; Genes; Genetic; Genomics; Goals; Heart failure; Hydroxylation; Individual; Knowledge; Learning; Link; Lipids; Malignant Neoplasms; Measurement; Measures; Metabolic; Metabolism; Methylation; Mission; Modification; Nucleic Acids; Output; Phenotype; Phosphorylation; Physiology; Population Heterogeneity; Post-Translational Protein Processing; Procedures; Process; Proteins; Proteomics; Provider; Publications; RNA; Renaissance; Research Personnel; Resources; Scientist; Shoulder; Signal Transduction; Signaling Protein; Surface; System; Technology; Testing; Work; experience; glycosylation; human genome sequencing; innovation; interest; multiple omics; new technology; next generation sequencing; protein degradation; protein expression; protein function; recruit; success; technological innovation; technology development

PROJECT SUMMARY – DRIVING BIOMEDICAL PROJECTS The high-level goals of our Resource are to accelerate the pace, depth, and accuracy of protein and PTM quantification, and to empower the scientific community to make new, impactful discoveries with these technologies. Initially, our TR&Ds were influenced by a clear need in the broad field of metabolism for new technologies that could accelerate discovery. Using our expertise in this field, we recruited world-class scientists who devised projects that served as robust testbeds for our TR&Ds. Many of these projects have been driven to completion while others have remained active and have influenced new TR&Ds. These interactions – and the broad utility of our technologies – have led to a natural expansion of our focus areas. We have also become better calibrated on our capabilities and bandwidth, allowing us to shoulder a broad swath of projects with efficiency and high success rates. For Cycle 2, two overarching DBP themes motivate our Resource’s technology development: Theme 1. New, metabolite-derived post-translational modifications (PTMs). The ability of PTMs such as phosphorylation and ubiquitylation to regulate signaling and protein turnover has long been established, and we have accelerated discoveries in this space through our original DBPs. Now, the scientific community is experiencing a renaissance of interest in how understudied modifications exert control over protein function in diverse cell biological contexts. These include methylation, acylation, glycosylation, and hydroxylation. Additionally, modifications to other biological species, such as glycosylated nucleic acids, are emerging as exciting, unexplored areas of biology. Many of these modifications are directly derived from central metabolites, thus intimately linking them to the metabolic state of the cell. Theme 2. Large-scale systems and multi-omics analyses to explore physiology and metabolism. The sequencing of the human genome, a watershed moment for biology, set a framework for deep understanding of genes and their functions. Next-generation sequencing has greatly accelerated our ability to measure the expression levels of these genes, thereby giving us a surface- level understanding of how cellular processes are changing under contrasting states. Nonetheless, myriad large- scale analyses have revealed a marginal protein/RNA correlation (R ~ 0.5), demonstrating the need for protein measurements of comparable depth and precision. Similarly, comprehensive analyses of lipid and metabolite abundance have revealed that protein expression alone is insufficient to predict metabolite levels, which are further affected by protein modifications and substrate availability, among other influences. Collectively, these observations have mandated the development of integrated, multi-omic analyses that provide a more holistic picture of a biological state.

项目摘要 - 驾驶生物医学项目 我们资源的高级目标是加快蛋白质和PTM的步伐，深度和准确性 数量，并赋予科学界有能力用这些新的，有影响力的发现 技术。最初，我们的TR＆D受到新代谢领域的明确需求的影响 可以加速发现的技术。使用我们在该领域的专业知识，我们招募了世界一流的科学家 谁设计了为我们的TR＆D提供强大的测试床的项目。这些项目中的许多已被驱动到 完成，而其他人仍然活跃，并影响了新的TR＆D。这些互动 - 以及 我们技术的广泛效用 - 导致了我们的重点领域的自然扩展。我们也已经成为 通过我们的功能和带宽更好地校准 效率和高成功率。对于第2周期，两个总体DBP主题激励我们的资源技术 发展：主题1。新的，代谢物的翻译后修饰（PTMS）。 PTMS的能力 长期以来已经建立了磷酸化和泛素化来调节信号传导和蛋白质更新， 我们通过原始DBP在这个领域加速了发现。现在，科学界是 对理解的修饰如何在蛋白质功能中施加控制的兴趣复兴 各种细胞生物学环境。这些包括甲基化，酰化，糖基化和羟基化。 另外，对其他生物种类（例如糖基化的核酸）的修饰正在出现为 令人兴奋的生物学领域。这些修饰中的许多直接来自中央代谢物， 这将它们与细胞的代谢状态紧密联系在一起。主题2。大规模系统和多摩斯 分析以探索生理和代谢。人类基因组的测序，一个分水岭 对于生物学，为对基因及其功能的深入了解设定了一个框架。下一代测序 极大地加速了我们测量这些基因表达水平的能力，从而使我们表面 对对比状态下细胞过程的变化的水平了解。但是，无数 比例分析表明，边缘蛋白/RNA相关性（r〜0.5），证明了对蛋白质的需求 可比深度和精度的测量。同样，脂质和代谢物的全面分析 丰度表明，仅蛋白质表达不足以预测代谢物水平， 还受到蛋白质修饰和底物的可用性的影响。总的来说，这些 观察结果要求开发综合的多摩变分析，该分析提供了更全面的 生物状态的图片。