Project 2: Aquatic Cyanobacteria Plant Collections

项目2：水生蓝藻植物收藏

基本信息

批准号：
10410425
负责人：
JIMMY ORJALA
金额：
$ 27.95万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
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/10410425
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

项目摘要

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.

该计划项目建议的总体目标是发现可以用作的天然产品抗癌药物来自各种自然来源。项目2，位于大学学院，大学芝加哥（UIC）的伊利诺伊州由植物，化学和生物学元素组成。主要目标项目2是发现蓝细菌的新铅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细菌和热带植物的自然产物结构将是抗癌铅的丰富来源。为了实现既定目标，针对项目2的具体目标是以下内容：1）获得，培养，提取和制备蓝细菌菌株的分数，然后序列选定菌株的基因组。我们每年将获得100个蓝细菌菌株。应变收集将关注美国上西部和美国大湖地区收集的样品，每个菌株将被培养，在Core 1可用的生物测试系统中提取，分离并提供用于生物学评估和项目1以及我们的外部生物测定提供者。作为一种互补和综合的方法，我们将序列和基因组矿山每年20菌株的基因组和菌株进行测序基于a）有希望的生物活性； b）基于趋化性或PCR筛选的优先级。 2）到分离并确定活性蓝细菌代谢物的结构，并提高铅的产量化合物。表现出有希望活性的提取物将使用活性监控的分级分馏。获得纯天然产品。结构表征的活性分离株将在该程序可用的生物测试系统。我们将重新分析大量任何候选化合物。为了提高产量，在必要时，我们将评估不同的耕种条件，并探索铅化合物的生物合成基因簇的异源表达，该基因将提供生产的替代来源。 3）获取拟议的所有植物材料计划项目。我们将每年从选定中获得150个充分记录和确定的植物样品世界国家。干燥的植物材料将提供给项目1，以进行进一步加工。我们还将重新收集植物材料，以大规模隔离活性化合物，需要更详细根据需要进行生物评估。