Project 2: Aquatic Cyanobacteria Plant Collections

项目2：水生蓝藻植物收藏

• 批准号: 10165646
• 负责人: JIMMY ORJALA
• 金额: $ 32.53万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10165646
• 关键词: Anabolism; Antineoplastic Agents; Biological; Biological Assay; Biological Testing; Botanicals; Chemicals; Chemistry; Chicago; Collection; Country; Cyanobacterium; Disease; Drug Kinetics; Elements; Evaluation; Flowcharts; Formulation; Fractionation; Fresh Water; Gene Cluster; Genome; Genomics; Goals; Great Lakes Region; Health; Heat-Shock Response; Human; Illinois; In Vitro; Individual; Institutes; Investigation; Laos; Lead; Libraries; Light; Malignant Neoplasms; Metabolism; Midwestern United States; Mining; Monitor; Natural Products; North Carolina; Ohio; Pathway interactions; Pharmacy facility; Phytochemical; Plants; Production; Protocols documentation; Provider; Puerto Rico; Research; Research Activity; Sampling; Solubility; Source; Structure; System; Taxonomy; Testing; Universities; Weight; Work; anti-cancer; base; college; drug development; experience; improved; in vivo; novel; novel anticancer drug; programs; stressor

The overarching goal of this Program Project proposal is to discover natural products that can serve as anticancer drug leads from diverse natural sources. Project 2, located at the College of Pharmacy, University of Illinois at Chicago (UIC), is comprised of botanical, chemical and biological elements. The primary goals for Project 2 are the discovery of new lead anticancer compounds from cyanobacteria and providing tropical plant material for Project 1, housed at The Ohio State University (OSU). The underlying hypothesis for Project 2 is that the diverse natural product structures from cultured non-marine cyanobacteria and tropical plants will be a rich source for anticancer leads. To achieve the stated goals the specific aims for Project 2 are as follows: 1) to obtain, culture, extract, and prepare fractions of cyanobacterial strains, and to sequence the genome of selected strains. We will obtain 100 cyanobacterial strains per year. The strain collection will focus on samples collected in the Upper Midwest and Great Lakes regions of the U.S. Each strain will be cultured, extracted, fractionated, and provided for biological evaluation in the biological test systems available at Core 1 and Project 1 as well as our external providers of bioassays. As a complementary and integrated approach, we will sequence and genome mine the genomes of 20 strains per year and strains will be selected for sequencing based on a) promising biological activity; and b) prioritization based on chemotaxonomy or PCR screen. 2) To isolate and determine the structures of active cyanobacterial metabolites, and to improve yields of lead compounds. Extracts showing promising activity will be fractionated using activity-monitored fractionation to obtain pure natural product(s). The structurally characterized, active isolates will be extensively evaluated in the biological test systems available to the program. We will re-isolate larger amounts of any candidate compound. In order to improve yields, when necessary, we will evaluate different cultivation conditions, and explore heterologous expression of the biosynthetic gene cluster of lead compounds, which will serve to provide an alternative source for production. 3) To acquire all plant materials that will be required by the proposed Program Project. We will obtain 150 fully documented and identified plant samples per year from selected countries of the world. The dried and milled plant material will be provided to Project 1 for further processing. We will also re-collect plant material for larger-scale isolation of active compounds requiring more detailed biological evaluation as needed.

该计划项目提案的总体目标是发现可用作 抗癌药物来自不同的天然来源。项目2，位于北京大学药学院 伊利诺伊大学芝加哥分校 (UIC) 由植物、化学和生物元素组成。主要目标 项目2是从蓝藻中发现新的先导抗癌化合物并提供热带植物 项目 1 的材料，位于俄亥俄州立大学 (OSU)。项目 2 的基本假设 是来自培养的非海洋蓝藻和热带植物的多种天然产物结构 将成为抗癌先导化合物的丰富来源。为了实现既定目标，项目 2 的具体目标如下： 如下：1)获取、培养、提取和制备蓝藻菌株的级分，并测序 选定菌株的基因组。我们每年将获得100株蓝藻。菌株收集将 重点关注在美国中西部上游和五大湖地区收集的样本。每种菌株都将被培养， 提取、分馏，并在核心 1 提供的生物测试系统中进行生物评估 项目 1 以及我们的生物测定外部提供商。作为一种补充和综合的方法，我们 每年将对20个菌株的基因组进行测序和基因组挖掘，并选择菌株进行测序 基于 a) 有前景的生物活性； b) 基于化学分类学或 PCR 筛选的优先顺序。 2) 至 分离并确定活性蓝藻代谢物的结构，并提高铅的产量 化合物。显示出有希望活性的提取物将使用活性监控分馏进行分馏，以 获得纯天然产品。具有结构特征的活性分离株将在 该计划可用的生物测试系统。我们将重新分离大量的候选化合物。 为了提高产量，必要时我们会评估不同的栽培条件，并探索 先导化合物生物合成基因簇的异源表达，这将有助于提供 替代生产来源。 3) 获取拟议项目所需的所有植物材料 计划项目。我们每年将从选定的植物中获得 150 个完整记录和鉴定的植物样本 世界各国。干燥和研磨后的植物材料将提供给项目1进行进一步加工。 我们还将重新收集植物材料，以大规模分离需要更详细信息的活性化合物 根据需要进行生物学评估。