Omics approaches for natural products discovery

天然产物发现的组学方法

基本信息

批准号：
8420619
负责人：
TIMOTHY S BUGNI
金额：
$ 27.19万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-01 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8420619
关键词：
Antibiotics Area Bacteria Biodiversity Biological Factors Chemicals Chemistry Coculture Techniques Communicable Diseases Communication Data Detection Drug Design Drug usage Environment FDA approved Florida Fractionation Gene Expression Regulation Generations Genomics Goals Habitats Health Human Laboratories Lead Libraries Marine Invertebrates Marines Methods Metric Mono-S Organism Outcome Pharmaceutical Preparations Planets Porifera Production Property Proteomics Puerto Rico Regulation Resources Source Structure System Systems Biology Technology Testing Therapeutic base cost effective design drug discovery drug production genome sequencing high throughput screening improved innovation metabolomics microorganism novel novel strategies oncology public health relevance screening small molecule tool transcriptomics tropical coastal water

项目摘要

DESCRIPTION (provided by applicant): The proposal aims to develop new approaches to natural products discovery. While much effort has been placed on designing drug-like synthetic screening libraries, limited efforts have been put forth to logically design natural product screening libraries in terms of improving novelty of hits and increasing drug-like or lead-like structures within the library. This project will evaluate logical natural product library design on the outcome of high-throughput screening, primarily in the areas of oncology and infectious disease. In particular, we will apply LCMS-based untargeted metabolomics to help guide library design. We will use metabolomics, genomics, transcriptomics, and proteomics to investigate interspecies interactions. Understanding the systems biology governing interspecies interactions and secondary metabolite production will uncover new mechanisms to activate cryptic clusters. The outcomes of this proposal will be: (i) a template for producing natural product libraries enriched in new/novel small molecules with drug-like properties; and (ii) a platform for rapidly determining organisms where interspecies interactions change secondary metabolite production.

描述（由申请人提供）：该提案旨在开发天然产物发现的新方法。虽然在设计类药物合成筛选文库方面付出了很多努力，但在提高命中的新颖性和增加文库内的类药物或先导类结构方面，在逻辑设计天然产物筛选文库方面付出的努力有限。该项目将评估逻辑天然产物库设计高通量筛选的结果，主要是在肿瘤学和传染病领域。特别是，我们将应用基于 LCMS 的非靶向代谢组学来帮助指导文库设计。我们将使用代谢组学、基因组学、转录组学和蛋白质组学来研究种间相互作用。了解控制种间相互作用和次级代谢产物产生的系统生物学将揭示激活神秘簇的新机制。该提案的成果将是：（i）用于生成富含具有类药物特性的新/新颖小分子的天然产物库的模板； (ii) 一个用于快速确定物种间相互作用改变次生代谢产物的生物体的平台。