New Actinomycetes & Other Gram-Positive Marine Bacteria

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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.