Scripps Institution of Oceanography at UC San Diego researcher William Gerwick.
Novel Technique Aims to Boost Marine Drug Discovery
High-tech analytical methods paired with nitrogen infusion allows researchers to track growth of compounds with biomedical potential
Scripps Institution of
Oceanography/University of California, San Diego
Looking to the seas to discover a new generation of cures
for a variety of diseases, researchers at UC San Diego have developed a new
method of deciphering how much biomedical potential marine organisms might offer.
In the March 29 edition of the Proceedings of the National Academy of
Sciences, a research team led by
Eduardo Esquenazi of Scripps Institution of Oceanography’s Center for Marine Biotechnology and Biomedicine (CMBB) and
of Biological Sciences describe a novel
approach to track how and when organisms produce molecules with potential human
benefit. The method employs nitrogen as a biological tracer along with MALDI
mass spectrometry, a laser-based analytical technique that can probe the inner
workings of organisms.
Marine organisms obtained
during field expeditions can produce exotic compounds unlike any from
terrestrial plants and animals. They can generate a natural toxic product, for
example, to ward off enemies in their habitat, yet the same substance might be
used by researchers to kill cancer or treat other human diseases. But
scientists hoping to extract such sources from sea life can encounter
roadblocks in pinpointing exactly how these natural compounds are produced.
The method described in the PNAS paper offers a new way to discover
and evaluate factors influencing the production of natural compounds and the
timing of such production. The scientists say the approach, which can be
executed with limited quantities, could become a novel tool in determining how
environmental factors influence natural compound production and cultivating the
compounds needed for drug discovery.
The research described in the
paper focused on a genus of cyanobacteria, tiny photosynthetic sea organisms,
and specifically jamaicamides, neurotoxic molecules discovered in 2002 off
Jamaica’s Hector’s Bay by Scripps and UCSD Professor William Gerwick and his
research team. Jamaicamides are thought to play a defensive role in nature,
possibly to ward off feeding from fish. Such molecules, the researchers say, may
also be effective against human cancers and tropical diseases.
continue to surprise us in their capacity to produce an amazing diversity of
exotic new natural product molecules; many of these are created utilizing
biochemical reactions that are new to science,” said Gerwick, a coauthor of the PNAS paper who holds a joint professorship in Scripps’ CMBB and the
UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences. “Perhaps
more importantly, some of these substances have powerful biological properties
relevant to treating human diseases, such as cancer, inflammation and
The researchers’ experiments
included adding nitrogen into laboratory cultures of cyanobacteria and testing
growth under various conditions, including exposure to degrees of light and
darkness. A technique called “MALDI-MS” (matrix-assisted laser desorption ionization
mass spectrometry), allowed them to track the nitrogen through the growth
process and identify how quickly nitrogen-containing molecules were created.
MALDI-MS approach could also be a valuable tool in efforts aimed at increasing
natural product yields from laboratory cultures of cyanobacteria or other
organisms with biomedical and biotechnological relevance, especially in cases
where compounds are found in low abundance,” the authors note in the paper.
“When we go into the field, we
will collect a lot of material and we’ll find a wide array of natural products.
Some of these are found in very low amounts. This method has allowed us to
monitor how quickly these particular cyanobacteria are making these molecules,”
said Adam Jones, a Scripps graduate student and coauthor of the PNAS paper.
“Cyanobacteria are valuable for
their pharmaceuticals but can also be harmful in the environment, in instances
such as cyanobacterial bloom events,” said Jones. “This method can be used for
identifying some of the triggers that cause the rates of compound production to
increase for drug discovery purposes, but it may also be useful in determining
how we can slow these rates to better understand how to limit negative
environmental impacts of cyanobacterial toxins.”
of the paper include Tara
staff research associate at Scripps’ CMBB and Pieter Dorrestein, associate
professor in the UCSD Skaggs School of
Pharmacy and Pharmaceutical Sciences.
for the research was provided by a graduate fellowship from the National
Institutes of Health Training Program in Marine Biotechnology, a graduate Fellowship from the Los
Angeles Chapter of
the Achievement Rewards for College Scientists (ARCS) Foundation, NOAA, the
California Sea Grant College Program and the National Institutes of Health.
-- Mario Aguilera
April 18, 2011