New Actinomycetes & Other Gram-Positive Marine Bacteria

新放线菌

• 批准号: 6924488
• 负责人: William Fenical
• 金额: $ 27.11万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6924488
• 关键词: Actinomycetales; antineoplastics; aquatic organism; biological products; biomedical equipment development; biotechnology; cooperative study; drug discovery /isolation; gram positive bacteria; liquid chromatography mass spectrometry; microorganism culture; microorganism resource /registry; miniature biomedical equipment; neoplasm /cancer chemotherapy; nuclear magnetic resonance spectroscopy; saltwater environment; sample collection; sedimentation

This is a new research component of the Crews-Novartis NCDDG Program focused on developing new and unique marine bacterial resources from which to derive new drugs for the treatment for cancer. Specific goals include the following: 1. To design and perfect the implementation of new miniaturized sampling devices to access deep-sea sediment samples in replicate numbers to depths of 5000 meters. These samples will be shared with our collaborators as part of the NCDDG Group's annual collecting expeditions. 2. To focus laboratory activities on the isolation of chemically-rich Gram-positive marine bacteria, concentrating on two main groups, the high G+C Gram-positives in the Order Actinomycetales and the low G+C Gram-positives in the Phylum Firmicutes, and to prescreen cultures for their chemical novelty by LCMS analysis. 4. To cultivate in excess of 500, "chemically-novel" (by chemical prescreening), Gram-positive bacteria per year, to adsorbent extract and fractionate these cultures, and to generate "peak libraries" in 96-deep well plate formats, at standardized concentrations (2.5 mg / well) for bioassay at Novartis. 5. By refering to the "active wells", to structurally define the active compound(s) using combined spectral and chemical approaches, including structure modification and the application of mass spectrometry, one- and two-dimensional NMR techniques, and other spectral and chemical methods. 6. To support the Novartis preclinical development program by large-scale cultivation (up to 200 liters) of the active strains, and by isolation and purification of the active compounds in milligram to gram quantities.

这是Crews-Novartis NCDDG计划的一个新的研究组成部分，专注于开发新的和独特的海洋细菌资源，从中获得治疗癌症的新药。具体目标包括： 1.设计和完善新的小型化取样装置，以便在5 000米深处多次获取深海沉积物样品。这些样本将作为NCDDG集团年度收集考察的一部分与我们的合作者分享。 2.将实验室活动的重点放在分离富含化学物质的革兰氏阳性海洋细菌上， 集中于两个主要的组，放线菌目中的高G+C革兰氏阳性菌和厚壁菌门中的低G+C革兰氏阳性菌，并通过LCMS分析预筛选培养物的化学新奇。 4.每年培养超过500种“化学新”（通过化学预筛选）革兰氏阳性细菌，吸附提取并破碎这些培养物，并在96深孔板格式中以标准化浓度（2.5 mg /孔）生成“峰库”，用于Novartis的生物测定。 5.通过对“活性威尔斯”的分析，使用光谱和化学方法的组合，包括结构修饰和质谱、一维和二维NMR技术以及其他光谱和化学方法的应用，在结构上确定活性化合物。 6.通过活性菌株的大规模培养（高达200 L）以及活性化合物（毫克至克）的分离和纯化，支持诺华临床前开发项目。