Transcriptome Characterization of Medicinal Plants Relevant to Human Health

与人类健康相关的药用植物的转录组表征

• 批准号: 7857222
• 负责人: RODNEY B CROTEAU
• 金额: $ 145.94万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 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/7857222
• 关键词: Anabolism; Animal Model; Area; Biochemical; Biochemical Pathway; Biochemistry; Bioinformatics; Biological Factors; Biological Process; Carbon; Cell Culture Techniques; Cells; Chicago; Classification; Clinical Trials; Code; Communities; Complex; Computer software; DNA Sequence; Data; Databases; Deposition; Development; Engineering; Enzymatic Biochemistry; Enzyme Gene; Enzymes; Evaluation; Foundations; Gene Expression Profile; Genes; Genetic; Genetic Transcription; Genomics; Goals; Harvest; Health; Homologous Gene; Housing; Human; Illinois; Imagery; Investigation; Knowledge; Lead; Life; Medicinal Plants; Metabolic; Metadata; Modification; Molecular Biology; Molecular Genetics; Molecular Profiling; Museums; Online Systems; Orphan; Outcome; Pathway interactions; Pharmaceutical Preparations; Pharmacologic Substance; Phytochemical; Plant Sources; Plants; Process; Production; Public Health; RNA Sequences; Reaction; Regulation; Regulator Genes; Reporting; Research; Research Infrastructure; Research Personnel; Resources; Seasons; Source; Specificity; Specimen; Staging; Structure; Study models; Technology; Time; Tissues; Transcript; Universities; Validation; Variant; Work; base; cell type; chemical synthesis; comparative; cost; directed evolution; drug development; enzyme pathway; gene discovery; genetic variant; genome wide association study; improved; novel; public health relevance; success; synthetic biology; tool; transcription factor; user-friendly; voucher; web-accessible

DESCRIPTION (provided by applicant): Plants are the source of many important medicinal compounds and the diversity of plant species and biochemistry suggests that many more are potentially available. The current understanding of the formation of plant-derived medicinal compounds at the enzyme, gene and regulatory levels is very incomplete-not a single complex plant medicinal pathway has yet to be completely elucidated at both the enzyme and the regulatory level. Historically, most studies of plant-derived medicinal compounds have been very narrowly focused, typically devoted to very specific steps in a particular biosynthetic pathway. These investigations were often pioneering-the diversity of plant biochemistry contains many novel reactions-but they were also very labor- intensive. More recently, genome-wide studies of model plant species have resulted in an explosive increase in our knowledge of, and capacity to understand, basic biological processes. Working from the genetics to the biochemistry now provides the most efficient way to build a long awaited and urgently needed foundation for more effectively probing and exploiting plant medicinal compound biosynthetic pathways. Having a comprehensive medicinal plant transcriptome database would propel medicinal plant species from an orphan- like status into the limelight of plant biochemistry and molecular genetics. The long-term goal of this research is for the scientific community to understand the complete formation, storage and regulation of plant-derived medicinal compounds at the enzyme and gene level. Improved understanding will enable the development of alternate sources of known pharmaceuticals and of novel drugs. The objective of this proposal is to provide the research community with urgently needed infrastructure and resources to enable comprehensive studies of the most compelling and medicinally significant plant biosynthetic pathways. Its Specific Aims are 1) To validate carefully selected medicinal plants based on taxonomic classification, medicinal compound accumulation and target transcript analysis, 2) To conduct transcriptome profiling of these medicinal plants and 3) To disseminate the accumulated data to the scientific community in the form of a user-friendly database. The resultant database and tools for comparative analysis will lead to gene discovery and enable technologies in the broader medicinal plant field. It is expected that the entire field of plant-derived pharmaceuticals will be advanced to a higher, more comprehensive level of analysis as a result of the proposed research. This is significant because the results will provide researchers in the field of plant-derived pharmaceuticals with a publicly available database and search tools for comparative analyses of pathway enzyme-coding genes and regulatory factors. These tools will enable gene discovery, metabolic engineering, synthetic biology and directed evolution for the improved production of drugs and for the development of novel drugs. Taken together, we envisage that this will ultimately result in tangible long-term and meaningful benefits for public health. PUBLIC HEALTH RELEVANCE: This research is directed toward understanding the various regulatory and biochemical factors that control medicinal compound formation, transport and storage in medicinal plants. Success in this area offers the promise of providing less expensive and/or novel medicinals that could positively impact the lives of hundreds of millions of people.

描述（由申请人提供）：植物是许多重要药用化合物的来源，植物物种和生物化学的多样性表明可能有更多的药用化合物。目前对植物源性药用化合物在酶、基因和调控水平上的形成的理解是非常不完整的，没有一个复杂的植物药用途径在酶和调控水平上都还没有完全阐明。从历史上看，大多数植物源性药用化合物的研究都非常狭窄，通常致力于特定生物合成途径中非常具体的步骤。这些研究往往是开创性的植物生物化学的多样性包含许多新的反应，但他们也非常劳动密集型。最近，对模式植物物种的全基因组研究使我们对基本生物过程的了解和理解能力爆炸性地增加。从遗传学到生物化学的研究为更有效地探索和开发植物药用化合物生物合成途径提供了最有效的方法，为建立期待已久的和迫切需要的基础。拥有一个全面的药用植物转录组数据库将推动药用植物物种从孤儿般的地位进入植物生物化学和分子遗传学的聚光灯下。这项研究的长期目标是让科学界在酶和基因水平上了解植物源性药用化合物的完整形成、储存和调控。提高认识将有助于开发已知药物和新药的替代来源。该提案的目的是为研究界提供迫切需要的基础设施和资源，以全面研究最引人注目和最具医学意义的植物生物合成途径。其具体目标是：1）根据分类学分类、药用化合物积累和靶转录物分析来验证精心挑选的药用植物，2）对这些药用植物进行转录组分析，3）以用户友好的数据库形式向科学界传播积累的数据。由此产生的数据库和比较分析工具将导致基因发现，并使技术在更广泛的药用植物领域。预计由于拟议的研究，整个植物源药物领域将提升到更高、更全面的分析水平。这是重要的，因为这些结果将为植物源药物领域的研究人员提供一个公开的数据库和搜索工具，用于比较分析途径酶编码基因和调控因子。这些工具将使基因发现、代谢工程、合成生物学和定向进化成为可能，以改进药物生产和开发新药。我们预计，这最终将为公共卫生带来切实的长期和有意义的好处。 公共卫生关系：本研究旨在了解控制药用植物中药用化合物形成、运输和储存的各种调节和生化因子。这一领域的成功提供了提供更便宜和/或新颖药物的希望，这些药物可能会对数亿人的生活产生积极影响。