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

Grant Number: 5U41AT008718-04
PI Name: MacMillan
Project Title: MacMillan: Overall; The Center for High-Throughput Functional Annotation of Natural Products (McMillan)

Abstract: 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. PUBLIC HEALTH RELEVANCE: The overarching goal of this CANPIT proposal is use innovative phenotypic screening approaches to identify the mechanisms of action of botanicals and natural products. As the use of botanicals and dietary supplements continues to rise in the United States we still have relatively little understanding of the molecular basis of how these extracts and compounds work. This has profound implications on the efficacy and safety of these products. The approaches described as part of our center will provide a molecular understanding for a large number of botanicals and natural products. Through our data coordination and dissemination component, the results from our studies will be available to the greater scientific community and consumers of botanical and dietary supplements

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