There are a number of foundational questions that remain unanswered as to how botanical natural products interact with complex biological systems. The specific big picture questions we will address are: (1) Do botanicals work through synergistic interactions? (2) Do botanicals have well defined mechanisms of action? Understanding the complex relationships of the mode of action of natural products, coupled with the difficulty in obtaining a complete picture of the chemical makeup of the samples, are rate limiting factors in our understanding of the utility of these materials. Botanicals exemplify the complexity faced by the field of natural products, as these complex mixtures can have dramatic variation in the constituents and concentration of individual compounds across samples based on the supplier, growth conditions and preparation.
As the complex mixture or individual metabolites are used in a biological context, host and microbe metabolism can further expand the chemical complexity and play a role in generation of the biological relevant chemical entity.
To overcome the existing limitations, rigorous and sustained efforts are needed to develop tools at the chemical and biological level. This Center has been established to unite mechanism of action technology, untargeted metabolomics, botanical expertise, data analytics and the informatics strengths of UC-Santa Cruz, Simon Fraser University and UNC Greensboro to produce an end-to-end pipeline to address these challenges
Integrated Biological and Chemical Approach
Our approach brings together gene expression-based and high content imaging-based platforms, along with new approaches to acquisition and data analysis of metabolomics data to generate high quality data that can be used to drive molecular signatures of natural products. To leverage the power of the rich molecular information that can be obtained using these and other platforms, the third aspect of the HiFAN program is the development of bioinformatic tools and on-line resources that can be used by the community to investigate chemical/biological relationships. Examples of the tools that we have built include the FUSION database and the NP Atlas.