New Actinomycetes & Other Gram-Positive Marine Bacteria

这是CROWS-Novartis NCDDG计划的一个新的研究组成部分，重点是开发新的和独特的海洋细菌资源，从这些资源中衍生出治疗癌症的新药。具体目标包括： 1.设计和完善新型小型化采样装置，可重复获取5000米以下的深海沉积物样品。这些样本将作为NCDDG集团年度收集探险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化学成分丰富的革兰氏阳性海洋细菌上， 集中于放线菌目中的高G-C革兰氏阳性菌和果蝇门中的低G-C革兰氏阳性菌两大类群，并通过LC MS分析对其化学新颖性进行预筛选。 4.每年培养超过500个“化学新奇”(通过化学预筛选)的革兰氏阳性细菌，对这些培养物进行吸附提取和分级，并以标准浓度(2.5毫克/孔)以96深孔板格式生成“峰库”，用于诺华公司的生物分析。 5.以“活性井”为参照，采用光谱和化学相结合的方法对活性化合物(S)进行结构确定，包括结构修饰和质谱学的应用，一维和二维核磁共振技术，以及其他光谱和化学方法。 6.支持诺华公司的临床前开发计划，大规模培养(高达200升)活性菌株，并分离和纯化毫克至克量的活性化合物。

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.