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DR. PHIL CREWS - University of California at Santa Cruz
The Research: Tropical Marine Research "At the Interface of Chemistry and Biology"
Phil Crews' lab at the University of California, Santa Cruz, focuses on the chemical ecology and
diversity of sponges from tropical marine environments, such as the South Pacific, and their
associated microorgansims. Crews' basic interest is in examining the structure and properties of
the nitrogen-containing compounds produced by these organisms. As an academic scientist at a state
university, his principal goal is to explore questions in chemical ecology that are not only at
the forefront of the field, but that are also suitable for training the next generation of
scientists. The applied side of his work is to discover and make available novel compounds that
may be leads for new pharmaceuticals or that might be used as molecular probes to help others
better understand fundamental ecological processes or advance their own drug discovery research.
Crews also views as a priority establishing and fostering relationships with researchers in the
exotic, remote regions where he has conducted extensive field collection work using scuba on some
of the planet's most beautiful coral reefs. His lab is currently supported mainly through
collaborative National Institutes of Health grants and to a lesser degree by biotech companies.
- VIDEO CLIP 1: "Research Interests of the Crews Lab"
Exploring the Biodiversity Triangle
In his field research Crews' targets the parts of the world with the highest marine diversity. Most marine
ecologists agree this is within the triangle formed by New Guinea, Singapore, and the Philippines, and Crews' team
has been to numerous sites within that region including Tonga, Fiji, and Vanuatu. He has also worked extensively in
the Caribbean. Currently the major focus of his research is the coral reefs of New Guinea.
Working in remote regions entails a number of significant challenges to any scientist, but especially one whose work
depends on long-term sample preservation, as is the case with natural products research. Even if a research boat
with generator and freezer can be found, keeping samples frozen for transport back to the U.S. can be challenging if
not impossible, as dry ice is not a common commodity in developing countries. Because of this, Crews has developed a
simple preservation method for samples that is unique among his colleagues. In the 1980s he discovered that if
freshly collected sponges are soaked in a 50% alcohol-50% water solution for 10-20 hours, and the solution
discarded, the sponges can then be stored at room temperature and still contain their natural products.
While in the field the group does use chromatography to ensure that bioactive compounds associated with sponges are
being collected, and to help identify sponges that may be of particular interest for collections. However, Crews
says they have intentionally limited high-tech experimentation while away from the lab. "We don't think of taking
HPLCs or mass spectrometers with us," says Crews, "We focus on keeping our heads underwater, being in nature, and
trying to learn from the ecology of the organisms we're collecting which will be relevant to chemistry we're engaged
in."
- VIDEO CLIP 2: "Simple Organisms and Complex Products; Global Centers of Marine Biodiversity"
Exploring Chemical Diversity
The main ecological question Crews' research is designed to address is: What is the ultimate source of the secondary metabolites
produced by sponges? So, when his group identifies compounds from a sponge with unique chemical architectures, they attempt to
determine who is responsible for actually producing the compounds, because there is a lot more in a sponge than sponge. Some of
those collected are as much as 50% bacteria.
Crews and his team have found evidence of astounding molecular structure among bacteria-derived compounds. One focus for the group
is the mixobacteria. Like other teams, they are still working to develop methods needed to effectively culture various species in
the lab. In addition, they are working to get and sequence the DNA of bacteria they cannot currently culture in hopes of
manufacturing the compounds they produce by recreating their biosynthetic pathways based on genetic information. "It's going to
take a lot of investigators," says Crews of this line of research, "and having one or more folks get lucky. We're hoping we'll be
the lucky ones."
- VIDEO CLIP 3: "Exploring Novel Microbial Natural Products"
Marine Fungi: Untapped Potential?
Crews' lab was among the first to realize and prove the concept that in addition to bacteria, sponges also contain an
abundance of fungi, and the group is also working to isolate fungi from marine sediments. In studying fungi, the initial
hope was that they would yield a whole new paradigm in molecular structures. This work is ongoing, and the group has already
made some promising finds from the roughly 100 fungi compounds they have isolated, a few of which have garnered interest
from biotech companies.
The challenge with marine fungi, according to Crews, is isolating and identifying fungi and related compounds that are not
also among those found on land, which have already been heavily studied.
Crews views tapping the potential of marine fungi as an area best suited to academic researchers such as himself who can
remain focused on the issue for the long-term, as opposed to biotech companies that require much faster payoff than appears
likely in this case.
Crews remains hopeful in the work overall. "I believe we're at the doorstep of interesting chemistry there, " says Crews of
marine fungi research, "so stay tuned. We should have breakthroughs and know whether this is going to work or not in the
next couple of years."
The Crews group has more recently branched into studies of bacteria and fungi isolated from marine sediments collected in
both shallow and deepwater. To date the work has focused on samples collected from Papua New Guinea, Vanuatu, San Diego, and
the Monterey Bay Canyon. The group uses a modified collection device they dubbed the "Crews" Missile to collect sediment
samples from as deep 2,000 feet.
The most Interesting Field Locations - And the Most Dangerous!
Crews' research has taken him to so many unique and exotic locations, that choosing a favorite is difficult, he says. Above
the water, he puts the Kingdom of Tonga at the top of his list and is especially fond of the country's music and artwork, a
selection of which is displayed at his house. Underwater, he says Fiji gets the highest marks so far. One of his favorite
spots is the Beqa (pronounced "Benga") Lagoon, where he first discovered the sponges from which the bengamides, a series of
promising bioactive compounds, were isolated. The lagoon includes a section of spectacular, cavernous passages he compares
to Manhattan side streets that are littered with sponges, gorgonians tunicates, and seaweeds. "It's been a privilege to be
able to go to these areas," says Crews.
As you might expect, Crews has an abundance of stories about interesting, exciting, and tricky situations in which he and
his team have found themselves while in the field. One of his most memorable experiences occurred in Papua New Guinea in
1999.
Around many of the country's islands, the accepted practice before diving is to spend some time in the nearest village
seeking permission from the chief and offering small gifts. Though the Crews team followed this protocol, their boat was
once mistaken for that of a group of tourist divers who had blatantly disregarded procedure. In retaliation, the islanders
began using slingshots to hurl rocks at the Crews team, and throwing spears from approaching outrigger canoes. Crews was on
the boat at the time, but several members were on the bottom diving.
"So, the challenge was to go down to about 70 or 80 feet and tell divers we need to exit ASAP, " says Crews. "We were trying
to figure out what the underwater signal should be for a native attack with slingshots and spears, " he says. Thankfully the
group was able to escape unharmed and clear up the misunderstanding with the village and so resume collections at the site.
- VIDEO CLIP 4: "Sometimes the Natives Get Restless!"
Educational Background
A child's chemistry set was Phil Crews' first exposure to the field that would ultimately become
his career. He recalls as a youngster completing some successful experiments with hydrogen
sulfide, also known as rotten egg gas, but did not go much further until he began college. As an
undergraduate at UCLA, he became interested in Nuclear Magnetic Resonance (NMR) and in his spare
time began using NMR spectra to attempt to derive compound structures. While in LA he also learned
how to surf and so expanded his fondness for the ocean. He says that, rather than academic
concerns, it was UC Santa Barbara's good surf spots that drew him there where he received a Ph.D.
doing NMR dissertation work.
His next career step took him east for a postdoctoral fellowship at Princeton. He missed the West
Coast, however, and soon returned there to join the UC Santa Cruz Department of Chemistry and
Biochemistry. In the 1970s, after about 4 years studying theoretically interesting molecules, he
decided to use spectroscopy to explore interesting marine-based problems. One of the catalysts to
this shift came when he found, in a book an undergraduate student brought to him, a chapter
explaining many wondrous biological properties of sponges, but that labeled their chemistry as
"unknown." He began working on sponges, but eventually had to put this line or research on hold
due in large part to the inadequacy of chemistry tools available at that time. After turning his
attention to seaweeds for several years, he was able to return to sponges by the 1980s and has
studied their chemistry ever since.
- VIDEO CLIP 5: "Educational Background"
- VIDEO CLIP 6: "An Organic Chemist Discovers Biology"
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