Rutgers New Jersey Agricultural Experiment Station [Center for Deep-Sea Ecology and Biotechnology]

Natural Product Discovery

The Center for Deep-Sea Ecology and Biotechnology is actively engaged in marine natural product discovery efforts.  Objectives may be summarized as follows:  (1) Collect organisms from a variety of deep-sea extreme environments (e.g., deep-sea hydrothermal vents, cold-water sulfide seeps, etc.); (2) screen extracts of newly-collected organisms and those within our extensive ultra-low frozen collections for a variety of bioactive compounds; (3) isolate and culture a myriad of microorganisms from a variety of extreme deep-sea habitats and screen these for bioactive compounds; (4) further fractionate and identify the structure of bioactive compounds; and (5) synthesize compounds for potential commercial development of pharmaceuticals, particularly those with anti-cancer activity.  Photo: Octopus.

CDSEB currently houses an extremely extensive ultra-low frozen collection of both metazoans and microbes from a wide variety of deep-sea hydrothermal vents and cold water seeps throughout the world's oceans.  In our ongoing efforts we are testing extracts of newly-isolated microbial stains form a wide variety of deep-sea hydrothermal vents and cold-water seeps (we maintain a culture collection of over 300 deep-sea microorganisms; one of the largest, if not the largest, of such collections in the world).  These organisms live in the most extreme environments on the planet and produce a vast array of, yet unknown, secondary metabolites.  These compounds have high potential for bioactivity that can be developed into commercial products such as drugs and antibiotics.  Much of our current research is focused on the testing of extracts for potential anti-cancer drugs, using an exclusive cell-based assay.  The assay, using cell lines developed in Dr. Eileen White's lab in the Rutgers' Center for Advanced Biotechnology and Medicine, is based on the knowledge that an important mechanism of both tumor progression and treatment resistance is achieved by tumor cells through the acquisition of defects in programmed cell death, an essential genetically-controlled cellular process also known as "apoptosis".  Viability is measured on two cell lines, one of which is apoptosis competent (W2), while the other is apoptosis deficient (D3).  The rationale for using these two cell lines to identify microbial metabolites with anti-cancer activity is that compounds that promote apoptosis will kill W2 cells, while D3 cells will survive.  Hence, if a given microbial compound kills W2 cells, but not D3 cells, we consider it an apoptosis inducer and thus a potential tumor suppressor.  For those extracts showing anti-cancer activity, we further fractionate and purify the materials to identify active compounds.  Efforts are then undertaken to elucidate the structure of these compounds with the goal of ultimately synthesizing them for potential commercial development.

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