National Center for Quantitative Biology of Complex Systems

国家复杂系统定量生物学中心

• 批准号: 10688022
• 负责人: JOSHUA J COON
• 金额: $ 125.16万
• 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/10688022
• 关键词: Acceleration; Achievement; Alzheimer' s Disease; Automobile Driving; Biological; Biology; Biomedical Research; Biomedical Technology; Biotechnology; Calibration; Cell physiology; Chromatography; Collaborations; Communities; Complex; Computer software; Data; Development; Diabetes Mellitus; Disease; Ensure; Evolution; Gene Expression; Genes; Genome; Genomics; Glean; Goals; Heart Diseases; Human; Internet; Knowledge; Laboratories; Large-Scale Sequencing; Legal patent; Lipids; Malignant Neoplasms; Mass Spectrum Analysis; Measurement; Metabolism; Mission; Molecular; Nucleic Acids; Pathogenesis; Physiology; Post-Translational Protein Processing; Process; Proteins; Proteome; Proxy; Publications; RNA; Regulation; Reporter; Research Personnel; Research Project Grants; Resources; Role; Scientist; Shoulder; Speed; System; Technology; Technology Transfer; Testing; Training; Training Programs; Transcript; Visit; Work; biological systems; community engagement; design; holistic approach; innovation; insight; interest; lipidome; material transfer agreement; metabolome; multiple omics; new technology; novel; success; tool; transcriptome

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.

项目摘要 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 科学家们研究生物学问题。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深入了解生物学和疾病发病机制。 然而，RNA水平只是一个高度复杂的生物学难题的一部分：基因是 细胞调节过程，而代谢物通常是最终产物和最终的生物效应物 分子。在表达后有许多层次的调节，它们在路径中微调生物系统 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 在这个过程中，国家复杂系统定量生物学中心（National Center for Quantitative Biology of Complex Systems） 为这些分子提供大规模的定量数据。生物技术研究资源 旨在加快蛋白质组、代谢组和脂质组定量的速度、深度和准确性。驱动 根据生物医学研究人员的需要，我们的使命是开发技术， 最全面和准确的生物状态报告。具体来说，我们将（1）扩展并最终 使我们的工作达到高潮，使全面的生物分子表征;（2）发展和结束我们的工作 实现高度多路复用的蛋白质组定量和（3）在开发新的 色谱和质谱平台，用于完全集成的多组学分析。 我们将在几个高影响力的生物医学研究项目的背景下开发这些技术 需要新的技术进步才能取得成功，并可以作为技术试验台。这些 推动项目包括两个中心主题。首先，响应生物医学研究人员的需求， 探索新出现的但知之甚少的生物分子及其PTM的作用，我们将针对项目 与新的代谢产物衍生的翻译后修饰有关。第二，我们认识到， 除了蛋白质测量，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，以充分了解他们感兴趣的生物系统，我们将与许多 这些项目使我们能够测试和改进大规模系统和多组学分析的技术， 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， 合作，最终目的是确保我们的技术的持续影响。我们所有的技术 是可持续的，我们已经建立了系统和非正式的机制，以实现我们的目标。 知识和创新的科学界。

项目成果

Infrared Multiphoton Dissociation Enables Top-Down Characterization of Membrane Protein Complexes and G Protein-Coupled Receptors.

• DOI: 10.1002/anie.202305694
• 发表时间: 2023-09-04
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Lutomski CA;El-Baba TJ;Hinkle JD;Liko I;Bennett JL;Kalmankar NV;Dolan A;Kirschbaum C;Greis K;Urner LH;Kapoor P;Yen HY;Pagel K;Mullen C;Syka JEP;Robinson CV
• 通讯作者: Robinson CV

Extracellular matrix scaffold and hydrogel derived from decellularized and delipidized human pancreas.

• DOI: 10.1038/s41598-018-28857-1
• 发表时间: 2018-07-11
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Sackett SD;Tremmel DM;Ma F;Feeney AK;Maguire RM;Brown ME;Zhou Y;Li X;O'Brien C;Li L;Burlingham WJ;Odorico JS
• 通讯作者: Odorico JS

In-depth Site-specific Analysis of N-glycoproteome in Human Cerebrospinal Fluid and Glycosylation Landscape Changes in Alzheimer's Disease.

• DOI: 10.1016/j.mcpro.2021.100081
• 发表时间: 2021
• 期刊: Molecular & cellular proteomics : MCP
• 作者: Chen Z;Yu Q;Yu Q;Johnson J;Shipman R;Zhong X;Huang J;Asthana S;Carlsson C;Okonkwo O;Li L
• 通讯作者: Li L

Adaptations to climate in candidate genes for common metabolic disorders.

适应常见代谢疾病的候选基因气候。

• DOI: 10.1371/journal.pgen.0040032
• 发表时间: 2008-02
• 期刊: PLOS GENETICS
• 影响因子: 4.5
• 作者: Hancock, Angela M.;Witonsky, David B.;Gordon, Adam S.;Eshel, Gidon;Pritchard, Jonathan K.;Coop, Graham;Di Rienzo, Anna
• 通讯作者: Di Rienzo, Anna

DNA-Scaffolded Synergistic Catalysis.

• DOI: 10.1021/jacs.1c10757
• 发表时间: 2021-12-22
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Pimentel, Edward B.;Peters-Clarke, Trenton M.;Coon, Joshua J.;Martell, Jeffrey D.
• 通讯作者: Martell, Jeffrey D.