ARRA: Advancing Drug Development in Medicinal Plants using Transcriptomics and Metabolomics

Medicinal plants produce a wealth of pharmaceutical compounds such as taxol, vincristine, and morphine. Unfortunately, the specialized secondary metabolic pathways leading to such compounds remain poorly understood and progress in elucidating and manipulating these taxonomically restricted metabolic pathways has been correspondingly slow. This has been exacerbated by the limited development of "omics"-level resources for medicinal plants, which has meant that as a group, research in medicinal species have not benefited to the same extent from the genomics revolution, as have research in model plants and agronomic crop species. This proposal describes the combined use of state-of-the-art sequencing technologies, metabolomics capabilities, and bioinformatics to develop an unrestricted, public resource to address this growing gap in our knowledge base of species-specific plant metabolism and accelerate the identification and functional analysis of genes involved in natural product biosynthesis in 20 widely used medicinal plant species. This resource will provide the research community with user-friendly access to the DNA sequences and expression profiles of each plant's transcriptome and associated metabolome, which we anticipate will have a translational effect on drug development. To achieve this goal, we will utilize next generation sequencing approaches to determine the near-complete set of mRNAs encoded by each medicinal plant species. Transcriptome profiling of up to 20 chemically diverse tissues/treatments per species using the RNA-Seq method from Illumina will be performed and correlated with metabolite profiles generated through LC-TOF and GC-MS for these same samples. All sequence and gene expression data will be deposited into NCBI and made available, along with metabolite profiling data at medicinalplantgenomics.msu.edu, a custom website developed by the research consortium. Thus, this NIH Grand Opportunities Grant will provide searchable and downloadable databases for medicinal plant gene sequences, expression profiles and metabolites that can be accessed and utilized by the research community to facilitate discovery of the pathways and genes responsible for biosynthesis of key pharmaceuticals. High throughput sequencing of genomes and transcriptomes has revolutionized and accelerated the pace and progress of research across the life sciences and this proposal will for the first time extend these advances into the medicinal plant arena on a broad scale. PUBLIC HEALTH RELEVANCE: This proposal describes the combined use of state-of-the-art DNA sequencing technologies, metabolomics capabilities, and bioinformatics to develop an unrestricted, public resource to advance our knowledge base of species-specific plant metabolism and accelerate the identification and functional analysis of genes involved in natural product biosynthesis in 20 widely used medicinal plant species. This resource will provide the research community with user-friendly access to the DNA sequences and expression profiles of each plant's transcriptome and associated metabolome, which we anticipate will have a translational effect on drug development.