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

有充分证据表明，植物临床试验的成功结果很差，导致 更加努力地了解其活动背后的基本机制。虽然经常是这样 假设植物或其他复杂混合物通过协同或添加过程起作用，有 经证实的例子很少。人们越来越相信肠道微生物组代谢在以下方面的作用： 活性代谢物的产生，然而，相对较少的实验结果支持这一点。这是由 在相关生物测定中获得清晰的生物特征、准确定义 复杂混合物的化学组成，以及获取这些不同数据的信息学方法 类型在一起。该提案旨在通过发展和解决这些重要问题 技术平台的实施。在项目1中，我们将采用高度创新的基于正交细胞的 原代巨噬细胞、上皮细胞、原代神经元的高内涵表型筛选方法， 这将使我们全面覆盖被认为相关的信号通路和受体 到植物药。这些平台旨在将感兴趣的植物/生物活性分子与信息联系在一起 关于他们的分子目标。这些平台已被证明可以处理复杂的混合物 作为纯化合物，并得到允许整合的生物信息方法的开发的支持 正交生物活性。我们的第二个项目将利用非目标领域的发展 代谢组学，连同特征减少，有一个强大的管道来清楚地定义代谢组学的构成 复杂的混合物。我们的第三个项目专门解决了协同作用和可加性的问题 开发使用综合生物和化学特征的信息学方法 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和化学测定结果以生成化合物/活性图。该计划将 提供深入研究植物和天然产品的关键技术平台并提供工具 可供社区使用