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Ecological Leads for Drug Discovery from Marine Organisms

海洋生物药物发现的生态线索

基本信息

批准号：
9334338
负责人：
Julia Kubanek
金额：
$ 27.11万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9334338
关键词：
Algae Animal Model Antibiotics Antimalarials Automobile Driving Bacteria Biochemical Pathway Biodiversity Biological Biological Assay Biology Biomedical Research Central Nervous System Diseases Chemicals Chemistry Collaborations Collection Communicable Diseases Communities Complex Cues Developing Countries Development Disease Drug Kinetics Environment Exhibits Fiji Formulation Fractionation Generations Genetic Goals Growth Habitats High Pressure Liquid Chromatography Human Human Resources Invertebrates Island Language Lead Ligands Light Malignant Neoplasms Marines Mediating Medicine Metabolism Microbe Modernization Molecular Molecular Target Natural Products Neurodegenerative Disorders Nutrient Organism Parasites Pharmaceutical Preparations Pharmacologic Substance Pharmacology Population Population Density Production Property Red Algae Reproduction Role Sampling Secondary to Series Solomon Islands Source Specimen Structure Surface Symbiosis Taxonomy Techniques Testing Tissues Training Transcription Factor AP-1 United States Variant Work antimicrobial base coral cost drug candidate drug discovery fungus guided inquiry in vivo infectious disease treatment insight marine organism member metabolomics microbial microbial community microorganism neglect neglected tropical diseases nervous system disorder novel operation pathogen preclinical study pressure programs receptor response scaffold screening stereochemistry

项目摘要

Associate Program 2 Project Summary The goal of Associate Program 2 is to use ecological insights to guide the discovery of novel natural products with biological activity against a targeted group of diseases critical to developing nations and to the United States. In complex environments such as near-shore marine habitats, secondary metabolism has evolved over billions of years in response to intense selection pressure on organisms to solve critical challenges associated with survival and reproduction. In particular, tropical coral reefs host diverse microorganisms, algae, and invertebrates that use chemical cues and chemical defenses as a language driving interactions among and within species. Small organic molecules that are critical in mediating ecological interactions are strong candidates for new medicines targeting infectious disease caused by bacteria, fungi, and parasites, in addition to cancer and neurological disorders. We will explore understudied coral reef organisms including rare species of marine algae and invertebrates and microbes associated with algal and coral surfaces. We will apply ecological assays to uncover novel secondary metabolism, extending our previous work testing for antimicrobial, antiherbivore, and allelopathic compounds by adding microbial overlay and challenge assays to seek chemically rich microbes specialized as pathogens, mutualists, or commensals that produce unique secondary metabolites due to complex ecological interactions. Pursuit of lead drug molecules will be based on prioritized activity in a series of pharmacological screens relevant to infectious disease, tropical neglected disease, cancer, and neurodegenerative and CNS disorders. Identification of novel natural product structures will utilize modern spectroscopic techniques, leading to preclinical studies. Once our aims are met, we will have contributed novel pharmaceutical leads to the biomedical research community; revealed new molecular scaffolds and receptor-ligand interactions to the chemistry and chemical biology communities; learned new lessons on the roles of chemical cues and chemical defenses among marine macro- and microorganisms; applied new metabolomic and metabolic networking approaches to studying secondary metabolism in marine organisms; and trained a generation of scientific personnel in the U.S. and the South Pacific.

助理计划2 项目摘要助理计划2的目标是用生态洞察力来指导发现新的天然产品以生物活性对抗对发展中国家和美国至关重要的一组目标疾病各州。在复杂的环境中，如近岸海洋生物栖息地，次生代谢已经进化到数十亿年来，生物面临着巨大的选择压力，需要解决相关的关键挑战与生存和繁殖有关。特别是，热带珊瑚礁拥有各种各样的微生物、藻类和无脊椎动物，使用化学线索和化学防御作为一种语言，驱动和在物种内部。在调节生态相互作用中起关键作用的有机小分子很强此外，针对细菌、真菌和寄生虫引起的传染病的新药候选癌症和神经系统疾病。我们将探索未被充分研究的珊瑚礁生物，包括稀有物种海藻和无脊椎动物以及与藻类和珊瑚表面相关的微生物。我们会申请生态测试发现了新的次生代谢，扩展了我们之前的工作通过添加微生物覆盖和挑战分析来添加抗微生物、抗草食动物和化感作用化合物寻找化学成分丰富的微生物，作为病原体、互助体或共生体，产生独特的由于复杂的生态相互作用而产生的次生代谢产物。对含铅药物分子的追求将基于在一系列与传染病相关的药理筛选中优先考虑的活动，热带被忽视疾病、癌症、神经退行性疾病和中枢神经系统疾病。天然产物新结构的鉴定将利用现代光谱技术，进行临床前研究。一旦我们的目标实现，我们将为生物医学研究界贡献了新的药物线索；揭示了新的分子化学和化学生物界的支架和受体-配体相互作用；学习新知识关于化学线索和化学防御在海洋宏观和微生物中的作用的课程；应用新的代谢组学和代谢网络方法研究海洋次生代谢并在美国和南太平洋地区培养了一代科学人员。