The Philippine Mollusk Symbiont ICBG (PMS ICBG) project links a biodiversity survey of marine mollusks in one of the world's hotspots of diversity, with enzyme and drug discovery aimed at bacterial symbionts of mollusks. Mollusks constitute the most diverse marine eukaryotic group, occupying virtually every possible ecological niche. The diversity of microbes associated with mollusks is equally vast.
Within the mollusks, three particular groups exhibit what we believe to be the highest biotechnological and scientific potential: the bivalve family Teredinidae (genus Teredo) and the gastropod superfamilies Conoidea (genus Conus) and Muricoidea (genus Murex). The project directly addresses the goals of the ICBG program and will yield drug leads in central nervous system, cancer and antimicrobial areas, as well as strains and enzymes for cellulosic biofuels production. The project will characterize symbiotic diversity and pharmaceutical and biofuels potential of mollusk-associated bacteria in a comparative framework for the first time.
The plan focuses on training, conservation, and the development of drug discovery and biofuels programs within the Philippines. The Republic of the Philippines represents a unique nexus of exceptional biodiversity, dense human population with pressing societal and energy needs, consequent urgent conservation goals, and government and private sector commitment to education and technology to harness national human and natural resources for a sustainable future.
The project is led by Margo Haygood, marine microbiologist, University of Utah, in association with Gisela Concepcion, marine natural products chemist, Marine Science Institute, University of the Philippines, Baldomero Olivera, biochemist, and Eric Schmidt, natural products chemist and biochemist, both of University of Utah, Gary Rosenberg, evolutionary biologist, Academy of Natural Sciences, Philadelphia, and Daniel Distel, marine microbiologist, Ocean Genome Legacy.
Principal Investigator and Associate Program 3 leader
Dr. Haygood is a marine microbiologist by training, with 30 years of experience investigating marine bacterial symbioses. She is well known for her in-depth studies of marine invertebrate symbioses, particularly the association between the bryozoan Bugula neritina and its symbiont Endobugula sertula, which produces the anti-cancer bryostatins to protect the bryozoan's offspring from predation. Due in large part to the work of her group, this is now the best-understood example of a marine chemical defense symbiosis. Innovative use of laser-scanning confocal microscopy to characterize symbioses by localization of both symbionts and symbiotic compounds is a important recent contribution. She has led field expeditions in Japan, Honduras, Palau and Egypt, and has served on the board of directors of the Coral Reef Research Foundation, Palau.
Prior to her academic career, she was a program manager for the Office of Naval Research, where she managed extramural molecular biology and microbiology programs worth over 30 million dollars annually in current value, and received recognition for her management performance. The NIH, NSF, USDA, California and Oregon Sea Grant (NOAA) and the Office of Naval Research have funded her research program. As PI, Dr. Haygood will be responsible for the overall administration of the PMS ICBG including financial management, stewardship of data and resources, organizing communication and reporting, tracking of leads and ensuring compliance with legal requirements and broad standards of research and financial integrity. She will also lead AP 3, the OHSU/OGL/UU/UP collaboration investigating the potential of shipworm symbionts for discovery of drug leads and cellulolytic enzymes for biofuels production.
Associate Program 2 leader
Dr. Schmidt is a leader in marine natural products chemistry of bacterial symbionts. His group pioneered cloning, expression, and engineering of a secondary metabolite biosynthesis pathway of an uncultivated symbiont of a marine invertebrate. He brings strong expertise in marine natural products structural elucidation, combined with biochemistry and molecular biology of bacterial secondary metabolite production. Dr. Schmidt's research program has been funded primarily by the NIH. Dr. Schmidt will be responsible for leading chemical characterization of lead compounds from the screening program, including training Filipino researchers to become self-sufficient in using instrumentation provided by PharmaSeas. He will provide expertise in biosynthesis to all participants. He will lead AP2, investigating mollusk symbionts as sources of drug leads.
Participant, Associate Program 2
Dr. Olivera is an internationally recognized biochemist whose investigation of neuroactive peptides from cone snail venom is a classic example of elegant basic biomedical science linked to marine biotechnology. He brings expertise on central nervous system physiology and biochemistry together with deep knowledge and experience of marine biology research in the Philippines.
Dr. Olivera's research program has been funded primarily by the NIH. Dr. Olivera will lend his expertise in neurobiology to identifying central nervous system leads particularly to AP2.
University of Utah: The University of Utah is the leading Carnegie Research I University in the Intermountain West, and emphasizes interdisciplinary and interactive opportunities via the Huntsman Cancer Institute, the Pediatric Pharmacotherapy Program, the Brain Institute, and many departments in the School of Medicine, College of Engineering, and College of Pharmacy, where AP2 will be based. The College of Pharmacy recently ranked second in NIH support among colleges of pharmacy in the US after UCSF. This solid research base is backed by shared core facilities providing access via expert operators to the most advanced equipment in chemistry and biology, as described in Resources. In drug development, Utah features the NIH Anticonvulsant Drug Development Program, a large zebrafish core facility that is focused on drug screening and mechanism, and a mouse transgenic core facility based upon the research of recent Utah Nobelist M. Capecchi. An emphasis on graduate education has led to the creation of several cross-disciplinary training programs that bring more than 60 graduate students to the University per year, in addition to the usual department-centered direct admissions process. The shared core facilities and training programs reinforce the university emphasis on interaction between departments and colleges.
Associate Program 4 leader
Dr. Concepcion is a leading Filipino marine natural products chemist. Her focus has been on marine natural products from sponges and their associated microbes, contributing to discoveries of anti-cancer and anti-malarial marine natural products and leading to numerous publications and patents. Her group has already amassed a collection of approximately 2000 marine microbial isolates, and she is a leader in the planned PharmaSeas project. Dr. Concepcion will be responsible for administration and direction of all activities taking place through UP, including recruitment of Filipino students, coordinating sample collection and supporting AP1, the mollusk biodiversity survey, and interfacing with government, conservation and private sector partners. As leader of AP4, she will organize and coordinate the screening program and work with the data manager to ensure that the NAPIS database is kept current. She will oversee archiving of samples and isolates in Philippine collections, and be responsible for interfacing with PharmaSeas.
University of the Philippines, Diliman, Marine Sciences Institute: The UPMSI has existing capabilities and facilities to pursue marine drug discovery with a very strong program in marine natural products chemistry and biotechnology. It recently received significant funding from the UP Administration (UP Diliman and UP System) to complete the Marine Biotechnology wing on the third floor of the UPMSI Building. This wing consists of three modules of laboratory facilities and offices for research on 1) Genomics and Genetic Manipulation, 2) Proteomics, Natural Products and Drug Discovery, Biopolymer and Bioorganic Chemistry, 3) Biochemistry, Toxinology and Pharmacological Studies. This new extensive facility will become available for use soon in addition to existing working Marine Biotechnology and Natural Products laboratories at UPMSI. The planned PharmaSeas drug discovery program will ultimately provide major chemistry instrumentation in these new laboratories. This instrumentation can be used to support the PMS ICBG in the latter part of the project, after a chemistry training phase at the University of Utah. The University of the Philippines Marine Science Institute, Marine Chemical Ecology and Biodiversity, and Marine Natural Products Groups pioneered in conducting the public consultation and PIC (prior informed consent) process among local communities living near marine collection sites. The UPMSI's commercial research agreement and bioprospecting activities have been cited by NGOs as a model of compliance with government regulations and of good bioprospecting practices.
Associate Program 1 Leader
Dr. Rosenberg is a distinguished malacologist with special expertise in Indo-Pacific marine mollusks. He has played a leading role in the development of electronic databases documenting and disseminating information on mollusk systematics. A particularly relevant accomplishment is the Biotic Database of Indo-Pacific Marine Mollusks . His work in creating a taxonomic key to 500 species of Jamaican land snails via Discover life is a prime example of a tool that is accessible and valuable to researchers, conservation workers and the general public. The Discover Life mission is to assemble and share knowledge in order to improve education, health, agriculture, economic development, and conservation throughout the world. Discover Life provides free on-line tools to identify species, share ways to teach and study nature's wonders, report findings, build maps, process images, and contribute to and learn from a growing encyclopedia of life that now lists almost 1,200,000 species. Their mission is to provide everyone with the information needed to reduce disease, increase food production, stop destructive species, protect endangered ones, and enjoy rather than struggle with nature. Dr. Rosenberg's research program has been funded by the Sloan Foundation and the National Oceanographic Partnership Program. As AP1 leader, Dr. Rosenberg will be responsible for the design and direction of the AP1 biodiversity survey, and ensuring the proper archiving of taxonomic samples. He will provide support to the overall project via specimen identification, and advice on sample choice.
Academy of Natural Sciences, Philadelphia: The Academy of Natural Sciences is Philadelphia's Natural History Museum. The Academy is the oldest continuously operating natural science research institution and museum in the Americas. The collection of recent mollusks at The Academy of Natural Sciences of Philadelphia (ANSP) is the oldest in the country, and the second largest catalogued one in the world. It currently has about 500,000 catalogued lots containing about 10 million specimens, including 45,000-50,000 lots preserved in ethanol. Type specimens of more than 400 authors are represented in more than 12,000 type lots. ANSP has specimens from all over the world. Greatest strengths are in shallow-water marine mollusks from the tropical Indo-Pacific and the Western Atlantic and worldwide freshwater and land mollusks. ANSP also operates a research program in molecular systematics and ecology and in water quality monitoring.
Participant, Associate Program 3
Dr. Distel is the world's foremost expert on shipworm symbionts. He is the lead author on the classic species description of the cultivated symbiont Teredinibacter turnerae, and the discoverer, via state of the art cultivation-independent techniques, of cryptic diversity in shipworm symbionts. He has contributed to studies characterizing shipworm cellulases in vivo and in vitro and their expression in shipworm tissues, again revealing cryptic diversity. He is the leader of the ongoing NSF supported T. turnerae genome project that has provided key preliminary data for this work, and is senior author of the recent ground-breaking study using multi-isotope imaging mass spectrometry to directly image and measure nitrogen fixation by shipworm symbionts and transfer of fixed nitrogen to host cells. Dr. Distel is also the director of the non-profit Ocean Genome Legacy (see below). Dr. Distel's research program has been funded primarily by NSF. Dr. Distel will particpate in AP3, lending his expertise in shipworm symbiosis and participating in training. In addition he will be responsible for archiving appropriate tissue samples and bacterial isolates for public access via OGL, including devising a custom material transfer agreement for ICBG samples.
Ocean Genome Legacy: The Ocean Genome Legacy is a non-profit marine research foundation and biological specimen repository dedicated to exploring and preserving the wealth of information contained in the genes (DNA) of endangered, rare, unusual and ecologically critical marine organisms. Its mission is to acquire, authenticate, study, preserve, develop, and distribute genetic materials, biological specimens, information, technology, intellectual property, and standards needed to advance basic and applied research in marine conservation, natural products medicine and biotechnology. OGL's aim is to promote marine species and ecosystem conservation by providing research materials, technology, policy, educational materials and educational opportunities to academic, governmental, and non-governmental research organizations and to private industry. OGL is the repository of the original strain collection used for the formal taxonomic description of T. turnerae, the most extensive such collection in existence. OGL has agreed to develop custom material transfer agreements acceptable to Philippine government agencies and academic partners, which will apply to all ICBG samples and bacterial isolates.
Associate Program 1: Philippine marine mollusk biodiversity inventory
Rosenberg (leader), Concepcion, Olivera, Distel
This study is designed to provide the most pertinent information to support conservation goals, while supporting the focused research of APs 2 and 3 and the broad sampling required to provide a diverse set of bacterial isolates for AP4 by providing mollusk identification, suitable molecular investigations, sample archiving and dissemination of results via appropriate databases. The main sampling area will be on a transect from Cebu City to Zamboanga. Sampling will focus on coral reefs, mangroves, seagrass beds and intertidal flats. AP1 will provide training in taxonomy and cooperate in outreach.
Associate Program 2: Bacterial symbionts of gastropod molluscs: cultivation, drug discovery, and neurological activity
Schmidt (leader), Olivera, Haygood, Concepcion, Rosenberg
AP2 will focus on microbes associated with gastropod molluscs. It will provide chemistry support to AP3 and 4. It will provide training opportunities in microbiology, neurophysiology, biochemistry and structural elucidation.
Associate Program 3: Microbes associated with shipworms (Teredinidae) as sources of drug leads and cellulolytic enzymes
Haygood (leader), Distel, Schmidt, Concepcion, Rosenberg
AP3 will build upon an existing collaboration between Haygood and Distel's groups and that of Carlos Soares, Federal University of Rio de Janeiro. It will focus on specific symbionts as well as other associated microbes of shipworms and other herbivorous molluscs, and will characterize both secondary metabolites and enzymes for converting biomass to biofuels. The research will include both proven and innovative cultivation methods and state-of-the-art cultivation-independent community analysis and sophisticated microscopy. It will provide cultivation, and microscopy support to AP2 andAP4. It will provide training opportunities in microbiology, molecular biology and microscopy.
Associate Program 4: Screening of mollusk isolates for biological activity and enzymes for biomass conversion.
Concepcion (leader), Olivera, Schmidt, Distel
AP4 will combine existing assets in antimicrobial and anti-cancer screening in the Philippines with neurological, cancer and cellulase screens available in the US participants laboratories with the ultimate goal of transferring most screening technology to the host country by the end of the project. AP4 will also take a lead role in data stewardship and technology transfer to the private sector. It will provide the screening for the broad-based cultivation effort in the Philippines as well as support the focused efforts of AP2 and 3. It will provide training opportunities in marine biotechnology and conservation outreach. We plan to develop biodiversity education for primary school children in areas of high marine biodiversity. The ICBG team will build upon this foundation to help teachers and their students to monitor key molluscan species in their area. We hope to encourage students to become emissaries for conservation through their involvement as "citizen scientists" in reporting the state of their local biodiversity.
Universidade Federal do Rio de Janeiro research group of Carlos A.G. Soares (Dept. Genetica) is a collaborator on shipworm research. Soares Ph.D. student Amaro Trinidade Silva completed an extended research visit in the Haygood lab, and participated in the Teredinibacter turnerae genome annotation organized by Distel. Several publications are in preparation. A PMS-ICBG-linked FIRCA grant to support the collaboration "The secondary metabolome of bacterial symbionts of a tropical mangrove shipworm", is in review.
Suez Canal University faculty are collaborators on the shipworm project. Amro Hanora (Faculty of Pharmacy) completed an extended research visit to the Haygood lab, and participated in the Teredinibacter turnerae genome annotation organized by Distel. Several publications are in preparation. Ali Gab-Alla (Marine Science) is a long time collaborator who is co-PI with Haygood on a PMS-ICBG-linked USDA proposal to support the collaboration: "Red Sea shipworm symbionts: a source of novel bioactive metabolites" which involves faculty throughout the university.
Private Sector Partners
Conchology, Inc a company specializing in documented specimen shells located in Mactan Island, Philippines, generously allows access for PMS-ICBG students and researchers to their world class malacology library and Philippine specimen collection.
Poppe-Images, a provider of Philippine underwater photography, supplied images for this site.
World Register of Marine Organisms (WoRMS) provides an authoritative and comprehensive list of names of marine organisms, including information on synonymy and is the host for the global list of marine mollusks that PMS-ICBG helped to develop.
Marvin Altamia, University of the Philippines, Marine Science Institute, for graphic design.
Philippe Poppe and Roxan Guingao, Conchology, Inc. for assistance with website design and maintenance.
Positions are periodically available with Giselle Concepcion in the Marine Science Institute, University of the Philippines.
Contact Dr. Concepcion for more information: gpconcepcion[at]yahoo.com.