ICBG: "Training, Conservation and Drug Discovery using Panamanian Microorganisms

描述(申请人提供)：描述(申请人提供)：这项工作的总体目标是从巴拿马微生物中发现新的先导化合物，用于治疗癌症、中枢神经系统疾病、热带疾病和农业害虫，采用一系列创新的以及传统的生物分析方法。这一追求将与在一个生物多样性丰富但经济发展中的国家发展科学培训和能力建设密不可分，并将促进在生物多样性保护和基础设施发展方面取得切实成果。这项建议的具体目标将使我们能够实现这些目标：1)使用生态学概念来指导在生物多样性丰富的巴拿马国家内收集和培养内生真菌、蓝藻和其他异养细菌；2)生产这些收集和培养的材料的提取物，并通过适当的技术进行预分提，以产生具有更高滴度的有效成分的降低复杂性的筛选单元；3)通过AP2的人员和我们的合作者的努力，对下列治疗领域的提取物、预分提物和纯化合物进行生物筛选：癌症、中枢神经系统生物学、农业和热带疾病(疟疾、利什曼病和查格斯病)，4)利用分类学、计算机数据库和LC-MS数据的综合方法，在发现过程的早期阶段快速有效地分离已知和有害的化合物，5)使用生物测定指导方法分离在上述化验领域中确定的活性化合物，并使用高效和现代的光谱方法对这些物质进行表征，6)清点巴拿马陆地植物和海藻的生物多样性，并继续在巴拿马建立永久花卉收藏，7)发展和维护该计划所有参与者之间的正式合同，以解决知识产权问题，促进公平分享利益，并促进这些研究努力的数据和结果的广泛获取，8)帮助建设必要的科学基础设施和专业知识，以支持巴拿马的可持续药物发现计划；9)整合我们的药物发现和保护工作，从巴拿马生物多样性的海洋和陆地栖息地开发创新的新经济产品。这项提议寻求从巴拿马丰富的陆地和海洋微生物生物多样性中发现新的药物。我们发现工作的重点是癌症、中枢神经系统疾病、热带疾病以及农用化学品的新疗法。

DESCRIPTION (provided by applicant): DESCRIPTION (provided by applicant): The over-arching goal of this work is to discover new lead compounds from Panamanian microorganisms for the treatment of cancer, CNS disorders, tropical diseases, and agricultural pests, employing a spectrum of innovative as well as traditional bioassays. This pursuit will be inextricably connected to the development of scientific training and capacity building in a biodiversity-rich yet economically-developing country, and will foster tangible results in biodiversity conservation and infrastructure development. The specific aims of this proposal which will allow us to reach these goals are: 1) Use ecological concepts to guide the collection and culture of endophytic fungi, cyanobacteria and other heterotrophic bacteria within the biodiversity-rich country of Panama, 2) Produce extracts of these collected and cultured materials and prefractionate these by appropriate techniques to produce reduced complexity screening units which have active ingredients in increased titer, 3) Through efforts of personnel in AP2 plus our collaborators, to perform biological screens of extracts, prefractionated extracts, and pure compounds in the following therapeutic areas: Cancer, Central Nervous System biology, Agriculture, and Tropical diseases (malaria, leishmania and Chagas' disease), 4) Utilize an integrated approach of taxonomy, computer databases, and LC-MS data to rapidly and efficiently dereplicate known and nuisance compounds at early stages in the discovery process, 5) Isolate active compounds identified in the above assay areas using bioassay-guided approaches, and to characterize these substances using efficient and modern spectroscopic methods, 6) Inventory the biodiversity of terrestrial plants and marine algae in Panama, and to continue to build the permanent floral collections in Panama, 7) Evolve and maintain the formal contracts between all of the participants in this program to address intellectual property rights, promote equitable sharing of benefits, and to facilitate broad access to the data and results of these research endeavors, 8) Help build the scientific infrastructure and expertise necessary to support a sustainable drug discovery program based in Panama, and 9) Integrate our drug discovery and conservation efforts to develop innovative new economic products from the biodiverse marine and terrestrial habitats of Panama. This proposal seeks to discover new medicines from Panama's rich biodiversity of terrestrial and marine microorganisms. The focus of our discovery efforts are new treatments for cancer, CNS disorders, and tropical diseases as well as agricultural chemicals.