Discovering drugs, biofuels in tropical seas

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The project will concentrate its research in the Philippine archipelago whose waters are inhabited by an estimated 10,000 marine mollusk species, or about a fifth of all the known species, and are regarded by marine biologists as the world's epicenter of marine biodiversity. Mollusks are among the most diverse of marine animals and include shelled creatures like snails, clams and slugs.

The wide-ranging Philippine Mollusk Symbiont International Cooperative Biodiversity Groups, or PMS-ICBG, project aims to provide new information to catalog and preserve these diverse mollusk species while providing scientific opportunities for the Philippines. U.S. scientists will work closely with colleagues from the University of the Philippines to uncover interactions between mollusks and their bacterial partners. The project is expected to yield leads to potential central nervous system, cancer and antimicrobial drugs as well as enzymes for cellulosic biofuels production.

The National Science Foundation and the U.S. Department of Energy are also sponsors of the grant. The NSF supports basic research in marine science and biotechnology, and the DOE sees relevance to national energy needs because the shipworm, one species of mollusk the OHSU project will focus on, harbors bacteria that hold the promise of economically converting plant biomass into cellulosic ethanol, one of the holy grails in the quest for viable biofuels. The five-year PMS-ICBG grant is administered by the Fogarty International Center, with additional support from the National Institute on Mental Health, both of the NIH. The lead investigator is Margo G. Haygood, Ph.D., professor of marine and biomolecular systems in the Environmental and Biomolecular Systems division of the Department of Science and Engineering, OHSU School of Medicine. The team includes scientists from the University of the Philippines, the University of Utah, the Academy of Natural Sciences in Philadelphia, and Ocean Genome Legacy in Ipswich, Mass.

"This is a truly unique effort," said Edward Thompson, Ph.D., chairman of the Department of Science and Engineering, OHSU School of Medicine. "Looking at microbes in the ocean has enormous potential. It could contribute to the development of alternative fuels while at the same time opening a path for biomedical research in largely uncharted territory." Thompson's department is where environmental science and biomedical research come together at OHSU.

ICBG grants are designed to guide the discovery and development of pharmaceutical and other useful agents from the earth's plants, animals and microorganisms in such a way that the communities and the countries where those biological resources are found can benefit and, at the same time, promote development of the scientific capacity and economic incentives for conservation and sustainable harvesting of those resources. An estimated 40 percent to 50 percent of currently used drugs originate in natural products.

Haygood, a scientist at the Scripps Institution of Oceanography for 18 years before coming to OHSU, has worked on the microbiology of symbioses - the interaction between different biological species - for three decades and played a major role proving that bryostatin, an anti-cancer agent, is made by bacterial symbionts living in a marine animal. She will manage a collaborative effort with some of the world's leading authorities on mollusks and marine drug discovery.

The PMS-ICBG project has three research aims. The first is the methodical collection, identification and cataloging of mollusk species from the Philippines, and making this information freely available on the Internet. This effort will be led by Gary Rosenberg, Ph.D., curator and chairman of malacology (the study of mollusks) and an evolutionary biologist at the Academy of Natural Sciences in Philadelphia, who already has developed a biotic database documenting more than 25,000 species of Indo-Pacific marine mollusks.

The second aim is discovery of biologically active molecules from bacteria associated with marine mollusks. One target is bacteria isolated from gastropod mollusks, or snails, particularly the highly venomous cone snails found in Philippine waters. Leading this part of the project will be Eric Schmidt, Ph.D., a biochemist at the University of Utah. Noted neuroscientist Baldomero M. Olivera, Ph.D., also of the University of Utah and a Howard Hughes Medical Institute professor known for his groundbreaking research on neurotoxins produced by cone snails, will participate as well. Although based in the United States, Olivera maintains a laboratory in the Philippines. He contends that at least 700 compounds with potential medical efficacy can be found in each cone snail species. Named the Harvard Foundation's 2007 Scientist of the Year, his work led to development of Ziconotide, a commercial drug considered more effective than morphine in blocking out extreme pain.

Shipworms, the marine equivalent of termites and the scourge of wooden structures in estuarine and marine habitats worldwide, are the focus of the third aim. A relative of the clam, these animals host bacteria inside their gills that produce enzymes to help them digest wood and may prove useful for converting cellulosic biomass into biofuels. Cellulosic ethanol can be produced from cheap and abundant sources such as agricultural residue, fast-growing prairie grasses, lumber mill waste, and even municipal garbage. Food grains, mainly corn, are currently the primary source of ethanol, and its production requires almost as much fossil fuel as it saves while squeezing the food supply. But researchers have yet to find an enzyme that can rapidly and efficiently break down cellulose that can be relied on for industrial production of cellulosic ethanol. Haygood will lead the shipworm component of the project with the support of Daniel Distel, Ph.D., a marine microbiologist and executive director of the Ocean Genome Legacy Foundation, who has been studying shipworms for more than two decades.

The specimen collection, cultivation of microorganisms isolated from wild mollusks, screening and assay development, and chemical identification of compounds are activities that are interwoven throughout the project and will be performed at the Marine Science Institute, University of the Philippines, under the direction of Gisela P. Concepcion, Ph.D., a marine natural products chemist who was a key figure in establishing the Philippine PharmaSeas program, which facilitates collaborations focusing on natural products research.

Oregon Health & Science University