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

描述（由申请人提供）：描述（由申请人提供）：这项工作的首要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，采用一系列创新和传统的生物测定法。这一努力将与生物多样性丰富但经济发展中国家的科学培训和能力建设的发展密不可分，并将促进生物多样性保护和基础设施发展方面的切实成果。这一建议的具体目标将使我们能够实现这些目标，即：1）在生物多样性丰富的国家巴拿马，利用生态学概念指导内生真菌、蓝藻和其他异养细菌的收集和培养，（二）生产这些收集和培养的材料的提取物，并通过适当的技术对这些材料进行预破碎，以生产复杂性降低的筛选单元，其具有增加的活性成分。3）通过AP2工作人员和我们的合作者的努力，在以下治疗领域对提取物、预分级提取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、利什曼病和恰加斯病），4）利用分类学、计算机数据库、和LC-MS数据，以在发现过程的早期阶段快速有效地去复制已知和有害化合物，5）使用生物测定指导的方法分离在上述测定领域中鉴定的活性化合物，并使用有效和现代的光谱方法表征这些物质，6）清点巴拿马陆地植物和海洋藻类的生物多样性，并继续在巴拿马建立永久的花卉收藏，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，并促进广泛获取这些研究工作的数据和结果，8）帮助建立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。该提案旨在从巴拿马丰富的陆地和海洋微生物生物多样性中发现新药。我们的发现工作的重点是癌症，中枢神经系统疾病和热带疾病以及农业化学品的新疗法。

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.