MacMillan: Overall; The Center for High-Throughput Functional Annotation of Natural Products (McMillan)

 描述(由申请人提供)：天然产品高通量功能注释中心将加州大学圣克鲁斯分校和加州大学圣克鲁斯分校的天然产品化学、生物筛选、数据分析和生物信息学优势结合在一起，建立了一个天然产品研究中心，可以使用创新策略来研究植物和天然产品的生物效应。植物药和天然产物(混合物和纯化合物)的作用机制对于它们作为补充剂和治疗药物的使用和开发是一个限速挑战。植物药和膳食补充剂是一个特别的挑战，因为它们通常是复杂的混合物，可以改变单个化合物的成分和浓度。为了实现我们的目标，以适当的速度、广度和精度对植物和天然产品进行化学和生物表征，我们正在采用高度创新的基于正交细胞的高含量表型筛选方法来返回感兴趣的生物活性分子以及有关其分子靶标的信息。这些平台、细胞学分析(罗杰·林灵顿)和融合(约翰·麦克米兰和迈克尔·怀特)已被证明可用于复杂混合物以及纯化合物。虽然这两个平台都是高通量平台，本身就提供了独特的生物洞察力，但通过新的生物信息学方法结合输出将使我们能够更详细地探索天然产品。我们的交付成果将是数据和数据 分析管道，将有助于确定植物药和天然产品的作用机制(S)，研究协同和相加关系以及细胞/分子指纹的工具 植物药和天然产品。该中心的一个重要组成部分是向更广泛的科学界传播数据。将创建一些可搜索的、数据驱动的网站，使科学界能够访问主要数据。

 DESCRIPTION (provided by applicant): The Center for High-Throughput Functional Annotation of Natural Products unites the natural products chemistry, biological screening, data analytics and bioinformatic strengths of UTSW and UC Santa Cruz to generate a center for natural products research that can use innovative strategies to study the biological effects of botanicals and natural products. Assigning the mechanism of action to botanicals and natural products (mixtures and pure compounds) is a rate limiting challenge for their use and development as supplements and therapeutics. Botanicals and dietary supplements are a particular challenge, as these are often complex mixtures that can change in the constituents and concentration of individual compounds. To prosecute our goal of the chemical and biological characterization of botanicals and natural products with appropriate speed, breadth and precision, we are employing high innovative orthogonal cell-based high content phenotypic screening approaches to return bioactive molecules of interest together with information about their molecular targets. These platforms, cytological profiling (Roger Linington) and FUSION (John MacMillan and Michael White) have been demonstrated to work with complex mixtures as well as pure compounds. While both of these are high-throughput platforms that provide unique biological insight in their own right, combining the output through novel bioinformatic methods will allow us to probe natural products in greater detail. Our deliverables will be a data and data analytics pipeline that will help define the mechanism(s) of action of botanicals and natural products, tools to study synergistic and additive relationships and cellular/molecular fingerprints of botanicals and natural products. A vital component of this Center is the dissemination of data to the greater scientific community. A number of searchable, data driven website will be created to allow the scientific community access to the primary data.