Bioactive Natural Products from Deep Sea Hydrothermal Vent Organisms

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Oregon State University pharmacy scientist Mark Zabriski's 2010-2012 research project with Oregon Sea Grant

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  • Aspirin, penicilin, morphine, taxol Natural products are also of great importance as research biochemicals, useful for elucidating normal cellular processes as well as those present in pathological states. many of the essential tools of pharmacologists studying drug action are natural products, and these have had important roles in identifying novel targets for treating human disease.
  • By expanding the base of researchers investigating deep vents, the aim is to provide added support for studying these ecosystems and while also heightening awareness about the value of these regions and the need for their protections. The aim was to provide broad overviews of the research interests of each group and identify areas where these interests could possibly be combined to form new collaborative projects that would enhance the project portfolio of each group and open up new avenues for funding Capitalizes on relationship with scientists at OSU’s Hatfield Marine Science Center associated with the NOAA/PMELVents Program linkage to work with deep sea samples
  • Also Gain insight into role as signaling molecules in symbiosis and chemical ecology
  • There were 44 sequences for the phylum Actinobacteria for hydrothermal vents (0.6%). However, I am not sure if they are all within the Actinomycetales and most were unclassified. The deep-sea background search contained 615 hits for Actinobacteria with 508 belonging to Actinomycetales (6.4%). All sequences compiled from Ribosomal Database Project: Release 10 (For citations see http://rdp.cme.msu.edu/misc/citation.jsp)
  • Bioactive Natural Products from Deep Sea Hydrothermal Vent Organisms

    1. 1. <ul><li>Bioactive Natural Products from Deep Sea Hydrothermal Vent Organisms </li></ul><ul><li>Mark Zabriskie & Kerry McPhail </li></ul><ul><li>Department of Pharmaceutical Sciences </li></ul><ul><li>Oregon State University </li></ul>
    2. 2. Why Natural Products? <ul><ul><ul><li>Best source of chemical diversity and bioactive compounds </li></ul></ul></ul><ul><ul><li>‘ Secondary Metabolites’ – function in communication and protection </li></ul></ul><ul><ul><li>Have evolved to potently interact with specific molecular targets </li></ul></ul><ul><ul><ul><li>there is a purpose for their existence and biological activity </li></ul></ul></ul><ul><ul><li>~ 65% of antibacterial and anticancer drugs have a NP origin </li></ul></ul><ul><li>Constant need for new small molecules as drug leads </li></ul><ul><ul><ul><ul><li>Increasing drug resistance – esp. infectious diseases and cancer </li></ul></ul></ul></ul><ul><ul><ul><ul><li>NPs are best source of chemical diversity and bioactive compounds </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Chemical diversity directly correlates with biological diversity </li></ul></ul></ul></ul><ul><ul><ul><li>Screening unique organisms from rare/extreme ecosystems is the best way to discover novel natural products with important biological activities </li></ul></ul></ul>
    3. 3. Why Deep-sea Hydrothermal Vents? <ul><ul><ul><li>Vent systems are a highly unique ecological niche </li></ul></ul></ul><ul><ul><ul><ul><li>Organisms have not been examined for bioactive NPs </li></ul></ul></ul></ul><ul><ul><ul><ul><li>High likelihood of novel chemistry and bioactivity </li></ul></ul></ul></ul><ul><li>Project builds on relationship with scientists in the NOAA/PMEL Vents program </li></ul><ul><ul><li>Access to samples collected by submersible and ROV </li></ul></ul><ul><ul><li>Expands base of researchers working on vent systems </li></ul></ul><ul><ul><li>Enhances project portfolio and expands funding opportunities </li></ul></ul><ul><li>Aligns with NOAA’s Ocean Exploration program </li></ul><ul><ul><li>Bioprospecting is a research area recommended by the President’s Advisory Panel on Ocean Exploration. </li></ul></ul><ul><ul><li>The “New Ocean Resources” program encourages diverse sampling </li></ul></ul>
    4. 4. Goals <ul><li>Primary Goal : Assess potential of deep vent organisms as a source of novel small molecules for drug discovery </li></ul><ul><li>Specific Aims </li></ul><ul><ul><li>Obtain samples of deep vent microbial mats and invertebrates collected in collaboration with NOAA PMEL/Vents Program researchers </li></ul></ul><ul><ul><li>Create library of extracts, subfractions and pure compounds and evaluate biological activities </li></ul></ul><ul><ul><ul><li>Whole cell assays – cytotoxic, antimicrobial </li></ul></ul></ul><ul><ul><ul><li>Inhibition of biofilm formation </li></ul></ul></ul><ul><ul><ul><li>in vivo chemical genetics using a Zebrafish model </li></ul></ul></ul><ul><ul><li>Structurally characterize pure bioactive compounds </li></ul></ul>
    5. 5. Source Materials: Archival Samples <ul><li>Archived field-collected specimens </li></ul><ul><ul><li>Invertebrates – Prof. V. Tunnicliffe (University Victoria) </li></ul></ul><ul><ul><ul><li>Collected at various site in the Juan de Fuca Ridge system </li></ul></ul></ul><ul><ul><ul><li>Tube worms, palm worms, scale worms, limpets, etc. </li></ul></ul></ul><ul><ul><li>Microbial mats – Prof. C. Moyer (Western Washington University) </li></ul></ul><ul><ul><ul><li>Push cores and suction samples from Explorer Ridge and Mariana Island Arc </li></ul></ul></ul><ul><ul><li>Sample size permits testing for activity but not structural studies </li></ul></ul>Photos: www.pmel.noaa.gov/vents/nemo/explorer/bio_gallery/biogallery Photo: W. Chadwick Split limpet Temnocinclis euripes Tube worm Ridgeia piscesae Palm worm Paralvinella palmiformis bacterial mat
    6. 6. Source Materials: New Collections <ul><li>June 2009 cruise to Juan de Fuca Ridge </li></ul><ul><ul><li>R/V Atlantis carrying the submersible Alvin </li></ul></ul><ul><ul><li>First time vent organisms gathered specifically for natural product discovery </li></ul></ul><ul><li>Invertebrates and bacterial mats collected </li></ul><ul><ul><li>Quantities will permit structural studies </li></ul></ul><ul><ul><li>Culture samples taken for all bacteria </li></ul></ul>Figure: W. Chadwick Photo: K. McPhail
    7. 7. Deep Ocean Microbial Diversity Deep-Sea Bacteria n = 9,992 sequences Deep-Sea Hydrothermal Vent Bacteria n = 7,641 sequences Deep-Sea Archaea n = 1,995 sequences Deep-Sea Hydrothermal Vent Archaea n = 1,686 sequences
    8. 8. Expected Outcomes <ul><li>New chemotypes for drug discovery </li></ul><ul><li>Chemical probes for pharmacology and cell biology research </li></ul><ul><li>Leverage results to secure federal funding (NSF/NIH) supporting collection and biodiscovery </li></ul><ul><li>Gain insight into chemical ecology of vent communities </li></ul>
    9. 9. Acknowledgments <ul><li>Christopher Thornburg (OSU) </li></ul><ul><li>Bill Chadwick (HMSC/OSU) </li></ul><ul><li>Craig Moyer (WWU) </li></ul><ul><li>Verena Tunnicliffe (U. Victoria) </li></ul><ul><li>David Butterfield (PMEL/UW) </li></ul><ul><li>Jay Rasmussen & John Cassady </li></ul><ul><li>Oregon Sea Grant Program Development Award </li></ul><ul><li> </li></ul>
    10. 11. Preliminary Results <ul><li>Half the archival specimens have been fractionated and tested for biological activity </li></ul><ul><ul><li>Examined antimicrobial activity vs. S. aureus , E. coli and C. albicans </li></ul></ul><ul><ul><li>Activity observed for several crude and pre-fractionated extracts </li></ul></ul><ul><ul><ul><li>Majority of activity is antifungal </li></ul></ul></ul><ul><ul><li>Some samples also exhibit modest cytotoxic activity </li></ul></ul>
    11. 12. Preliminary Results <ul><li>Initial activity profile for 3 samples from June 2009 cruise </li></ul>Percent Inhibition
    12. 13. Table X: Activity profile for four microbial mat samples. Prioritized fractions are in bold

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