This renewal International Cooperative Biodiversity Group (ICBG) application aims to discover and develop small molecule drug leads from cultured marine microbes and diverse coral reef organisms collected from Fiji and the Solomon Islands. Drug discovery efforts will focus on four major disease areas of relevance to the United States and low and middle income countries: infectious disease including tuberculosis and drug- resistant pathogens;neglected tropical diseases including hookworms and roundworms;cancer;and neurodegenerative and central nervous system disorders. Screening in these therapeutic areas will be performed in collaboration with two major pharmaceutical companies, two highly respected academic groups, and various testing centers and government resources that are available to facilitate drug discovery and development. The acquisition of source material for this program will be linked to biotic surveys, informed by ecological investigations addressing the chemical mediation of biotic interactions, and enriched using ecology- based strategies designed to maximize secondary metabolite production and detection. The program is heavily invested in microbial genomics, chemical ecology, the application of innovative cultivation methods and bioassays, sequence-based methodologies, and modern molecular and analytical tools as methods to improve the efficiency with which new natural products are discovered. The structures of all new compounds will be solved using modern techniques in analytical chemistry and produced in sufficient quantities for pre-clinical evaluation. The research activities of the four associate programs (AP1-4) are highly synergetic and emphasize training and technology transfer to the host country. The research maximizes the expertise of the program leaders to generate collaborative and highly interdisciplinary research objectives that transcend traditional natural product drug discovery paradigms. These activities are coordinated through the Central Operations Core and facilitated by the South Pacific Center for Drug Discovery and Conservation. The CDDC will work with marine ecologists to develop more effective strategies for reef conservation and to expand the Locally-Managed Marine Area (LMMA) program, which has proven to be a highly effective method to bring village-level awareness to the importance of conservation and the maintenance of healthy coral reefs.
This ICBG program seeks to discover new drug leads for the treatment of cancer, drug resistant bacterial infection, neurodegeneration, and neglected tropical parasites. The source material will be acquired from cultured marine microbes, algae and invertebrates collected from diverse locations throughout Fiji and the Solomon Islands. The program employs innovative strategies that transcend traditional natural product discovery efforts including ecological insight and modern genomic and analytical techniques that improve the efficiency and effectiveness of the discovery process, while also providing management options for marine conservation and restoration.
| Beatty, Deanna S; Clements, Cody S; Stewart, Frank J et al. (2018) Intergenerational effects of macroalgae on a reef coral: major declines in larval survival but subtle changes in microbiomes. Mar Ecol Prog Ser 589:97-114 |
| Chhetri, Bhuwan Khatri; Lavoie, Serge; Sweeney-Jones, Anne Marie et al. (2018) Recent trends in the structural revision of natural products. Nat Prod Rep 35:514-531 |
| Clements, Cody S; Rasher, Douglas B; Hoey, Andrew S et al. (2018) Spatial and temporal limits of coral-macroalgal competition: the negative impacts of macroalgal density, proximity, and history of contact. Mar Ecol Prog Ser 586:11-20 |
| Clements, Cody S; Hay, Mark E (2018) Overlooked coral predators suppress foundation species as reefs degrade. Ecol Appl 28:1673-1682 |
| Machado, Henrique; Tuttle, Robert N; Jensen, Paul R (2017) Omics-based natural product discovery and the lexicon of genome mining. Curr Opin Microbiol 39:136-142 |
| Clements, Cody S; Hay, Mark E (2017) Size matters: Predator outbreaks threaten foundation species in small Marine Protected Areas. PLoS One 12:e0171569 |
| Letzel, Anne-Catrin; Li, Jing; Amos, Gregory C A et al. (2017) Genomic insights into specialized metabolism in the marine actinomycete Salinispora. Environ Microbiol 19:3660-3673 |
| Lavoie, Serge; Brumley, David; Alexander, Troy S et al. (2017) Iodinated Meroditerpenes from a Red Alga Callophycus sp. J Org Chem 82:4160-4169 |
| Steneck, Robert S; Bellwood, David R; Hay, Mark E (2017) Herbivory in the marine realm. Curr Biol 27:R484-R489 |
| Demko, Alyssa M; Amsler, Charles D; Hay, Mark E et al. (2017) Declines in plant palatability from polar to tropical latitudes depend on herbivore and plant identity. Ecology 98:2312-2321 |
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