The Center for High Content Functional Annotation of Natural Products

天然产物高内涵功能注释中心

• 批准号: 9923292
• 负责人: Nadja B Cech
• 金额: $ 100.37万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9923292
• 关键词: Address; Area; Back; Belief; Bioinformatics; Biological; Biological Assay; Biology; Botanicals; Cell Line; Cells; Chemicals; Clinical Trials; Communities; Complex; Complex Mixtures; Computer Models; Constitution; Cytology; Data; Data Analytics; Databases; Development; Disease; Epithelial Cells; Generations; Health; Health Benefit; Healthcare Industry; In Vitro; Informatics; Link; Maps; Medicine; Metabolic; Metabolism; Modeling; Modification; Molecular Target; Natural Products; Natural Products Chemistry; Neurons; Online Systems; Outcome; Phenotype; Process; Reagent; Role; Signal Pathway; Speed; Technology; Text; Work; base; data integration; experience; gut microbiome; in vivo; innovation; interest; macrophage; metabolomics; new technology; novel; programs; public health relevance; receptor; screening; success; synergism; technology validation; tool; web site

It has been well documented that the outcomes of success for botanical clinical trials have been poor, leading to greater effort into understanding the basic mechanisms underlying their activity. While it is often hypothesized that botanicals or other complex mixtures work through synergistic or additive processes, there are few proven examples. There is also growing belief to support the role of gut microbiome metabolism for generation of active metabolites, however, relatively few experimental results back this up. This is driven by limitations in obtaining clear biological signatures in relevant biological assays, in accurately defining the chemical constitution of complex mixtures, and in the informatics approaches to bring these disparate data types together. This proposal aims to address these important questions by the development and implementation of technology platforms. In project 1, we will employ highly innovative orthogonal cell-based high content phenotypic screening approaches in primary macrophages, epithelial cells, primary neurons, which will give us comprehensive coverage of signaling pathway and receptor that are believed to be relevant to botanicals. These platforms aim to link botanicals/bioactive molecules of interest together with information about their molecular targets. These platforms have been demonstrated to work with complex mixtures as well as pure compounds and are supported by the development of bioinformatic approaches that allow integration of orthogonal biological activity. Our second project will take advantage of developments in untargeted metabolomics, along with feature reduction, to have a robust pipeline to clearly define the constitution of complex mixtures. Our third project specifically addresses the question of synergy and additivity by the development of informatics approaches that use the comprehensive biological and chemical signatures generated in the other projects. In this project, we will develop universal tools that will allow the community to probe their own biological and chemical assay results to generate compound/activity maps. This program will deliver critical technology platforms for the in-depth study of botanicals and natural products and deliver tools that can be used by the community

有充分的文献证明，植物临床试验成功的结果很差，领先 更大的努力来理解其活动的基本机制。虽然经常 假设植物或其他复杂混合物通过协同或加性过程起作用， 很少有证实的例子。越来越多的信念支持肠道微生物组代谢的作用 但是，活跃的代谢产物的产生相对较少，实验结果很少。这是由 在相关生物学测定中获得明确的生物学特征的局限性，准确定义 复杂混合物的化学构成以及在提供这些不同数据的信息学方法中 一起类型。该建议旨在通过开发和 实施技术平台。在项目1中，我们将采用高度创新的正交细胞 原发性巨噬细胞，上皮细胞，原发性神经元的高含量表型筛选方法 这将为我们提供有关信号通路和受体的全面覆盖，这被认为是相关的 致植物。这些平台旨在将感兴趣的植物/生物活性分子与信息联系起来 关于它们的分子靶标。这些平台也已被证明可以使用复杂的混合物 作为纯化合物，并得到了允许整合的生物信息学方法的发展 正交生物学活性。我们的第二个项目将利用不靶向的发展 代谢组学，以及功能降低，具有强大的管道，以清楚地定义 复杂的混合物。我们的第三个项目专门解决了协同和加性问题 使用全面生物学和化学特征的信息学方法的开发 在其他项目中生成。在这个项目中，我们将开发通用工具，使社区能够 探测他们自己的生物学和化学测定结果，以生成化合物/活性图。这个程序将 提供关键的技术平台，以深入研究植物和天然产品，并提供工具 社区可以使用