Advancing Drug Development from Medicinal Plants using Transcriptomics and Metabo

利用转录组学和代谢促进药用植物药物开发

• 批准号: 7854387
• 负责人: Joe Chappell
• 金额: $ 302.76万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7854387
• 关键词: Address; Agricultural Crops; Aliquot; Anabolism; Animal Model; Arabidopsis; Arts; Bioinformatics; Biological Factors; Biological Sciences; Bone callus; Communities; Custom; DNA Sequence; Data; Data Set; Databases; Deposition; Development; Flowers; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Genes; Genome; Genomics; Goals; Grant; Health; Human; Knowledge; Libraries; Link; Maize; Maps; Medicinal Plants; Messenger RNA; Metabolic; Metabolic Pathway; Metabolism; Methods; Molecular Profiling; Morphine; Organism; Paclitaxel; Pathway interactions; Pharmacologic Substance; Plant Genes; Plant Leaves; Plant Model; Plant Roots; Plants; Process; Production; Quality Control; RNA; Reading; Relative (related person); Research; Resources; Rice; Sampling; Sorghum; Technology; Time; Tissue Sample; Tissues; Titanium; Transcript; United States National Institutes of Health; Variant; Vincristine; Work; biological research; candidate identification; drug development; gene function; genome sequencing; improved; insight; knowledge base; metabolomics; next generation; novel; public health relevance; stem; tool; transcriptomics; user-friendly; virtual; web site

DESCRIPTION (provided by applicant): 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.

描述(申请人提供)：药用植物产生丰富的药物化合物，如紫杉醇、长春新碱和吗啡。不幸的是，导致这类化合物的专门化次级代谢途径仍然知之甚少，在阐明和操纵这些分类受限的代谢途径方面的进展也相应缓慢。药用植物“组学”级资源的有限开发加剧了这种情况，这意味着作为一个整体，药用植物的研究没有像模式植物和农艺作物物种的研究那样从基因组学革命中获得同等程度的好处。这项提案描述了结合使用最先进的测序技术、代谢组学能力和生物信息学来开发一个不受限制的公共资源，以解决我们关于特定物种植物代谢的知识库中日益扩大的差距，并加快对20个广泛使用的药用植物物种的天然产物生物合成所涉及的基因的识别和功能分析。这个资源将为研究界提供用户友好的访问每个植物的转录组和相关代谢组的DNA序列和表达谱，我们预计这将对药物开发产生翻译影响。为了实现这一目标，我们将利用下一代测序方法来确定每个药用植物物种编码的近完整的mRNAs集。将使用Illumina的RNA-Seq方法对每个物种多达20个不同化学成分的组织/治疗进行转录组分析，并将其与通过LC-TOF和GC-MS为这些相同样本生成的代谢物分析相关联。所有序列和基因表达数据都将存储到NCBI中，并与代谢物图谱数据一起在MedicinalPlantgenomics.msu.edu上提供，这是一个由研究联盟开发的定制网站。因此，NIH的这一重大机遇拨款将为药用植物基因序列、表达谱和代谢物提供可搜索和可下载的数据库，研究界可以访问和利用这些数据库，以促进发现负责关键药物生物合成的途径和基因。基因组和转录本的高通量测序使整个生命科学的研究速度和进步发生了革命性的变化，并加快了研究进程，这一提议将首次将这些进展扩展到药用植物领域。 与公共健康相关：这项建议描述了结合使用最先进的DNA测序技术、代谢组学能力和生物信息学来开发一个不受限制的公共资源，以推进我们关于特定物种植物新陈代谢的知识库，并加快对20个广泛使用的药用植物物种的天然产物生物合成所涉及的基因的识别和功能分析。这个资源将为研究界提供用户友好的访问每个植物的转录组和相关代谢组的DNA序列和表达谱，我们预计这将对药物开发产生翻译影响。