Julia Kubanek, an associate professor at the Georgia Institute of Technology, holds samples of a tropical seaweed whose surface chemicals are being studied for their potential anti-malarial properties. Credit: Gary Meek
A group of chemical compounds used by a species of tropical
seaweed to ward off fungus attacks may have promising anti-malarial properties
for humans. The compounds are part of a unique chemical signaling system that seaweeds
use to battle enemies—and that may provide a wealth of potential new
Using a novel analytical process, researchers at the Georgia
Institute of Technology found that the complex anti-fungal molecules are not
distributed evenly across the seaweed surfaces, but instead appear to be concentrated
at specific locations—possibly where an injury increases the risk of fungal
A Georgia Tech scientist reported on the class of compounds,
known as bromophycolides, at the annual meeting of the American Association for
the Advancement of Science (AAAS). The research, supported by the National
Institutes of Health, is part of a long-term study of chemical signaling among
organisms that are part of coral reef communities.
“The language of chemistry in the natural world has been
around for billions of years, and it is crucial for the survival of these
species,” said Julia Kubanek, an associate professor in Georgia Tech’s School of Biology
and School of Chemistry and Biochemistry. “We can
co-opt these chemical processes for human benefit in the form of new treatments
for diseases that affect us.”
More than a million people die each year from malaria, which
is caused by the parasite Plasmodium falciparum. The parasite has
developed resistance to many anti-malarial drugs and has begun to show resistance
to artemisinin—today’s most important anti-malarial drug. The stakes are high
because half the world’s population is at risk for the disease.
A researcher holds a sample of the seaweed Callophycus serratus, which is being studied for potential anti-malarial compounds on its surfaces. Credit: Paige Stout
“These molecules are promising leads for the treatment of
malaria, and they operate through an interesting mechanism that we are
studying,” Kubanek explained. “There are only a couple of drugs left that are
effective against malaria in all areas of the world, so we are hopeful that
these molecules will continue to show promise as we develop them further as
In laboratory studies led by Georgia Tech student Paige
Stout from Kubanek’s lab—and in collaboration with California scientists—the
lead molecule has shown promising activity against malaria, and the next step
will be to test it in a mouse model of the disease. As with other potential
drug compounds, however, the likelihood that this molecule will have just the
right chemistry to be useful in humans is relatively small.
Other Georgia Tech researchers have begun research on
synthesizing the compound in the laboratory. Beyond producing quantities
sufficient for testing, laboratory synthesis may be able to modify the compound
to improve its activity—or to lessen any side effects. Ultimately, yeast or
another microorganism may be able to be modified genetically to grow large
amounts of bromophycolide.
The researchers found the anti-fungal compounds associated
with light-colored patches on the surface of the Callophycus serratus
seaweed using a new analytical technique known as desorption electrospray
ionization mass spectrometry (DESI-MS). The technique was developed in the
laboratory of Facundo Fernandez, an associate professor in Georgia Tech’s School of Chemistry and Biochemistry. DESI-MS
allowed researchers for the first time to study the unique chemical activity
taking place on the surfaces of the seaweeds.
As part of the project, Georgia Tech scientists have been
cataloging and analyzing natural compounds from more than 800 species found in
the waters surrounding the Fiji
Islands. They were
interested in Callophycus serratus because it seemed particularly
adept at fighting off microbial infections.
Julia Kubanek and Facundo Fernandez, both associate professors at the Georgia Institute of Technology, hold a molecular model of a potential anti-malarial drug under study. Credit: Gary Meek
Using the DESI-MS technique, researchers Leonard Nyadong and
Asiri Galhena analyzed samples of the seaweed and found groups of potent
anti-fungal compounds. In laboratory testing, graduate student Amy Lane found that
these bromophycolide compounds effectively inhibited the growth of Lindra
thalassiae, a common marine fungus.
“The alga is marshalling its defenses and displaying them in
a way that blocks the entry points for microbes that might invade and cause
disease,” Kubanek said. “Seaweeds don’t have immune responses like humans do.
But instead, they have some chemical compounds in their tissues to protect
Though all the seaweed they studied was from a single
species, the researchers were surprised to find two distinct groups of
anti-fungal chemicals. From one seaweed sub-population, dubbed the “bushy” type
for its appearance, 23 different anti-fungal compounds were identified. In a
second group of seaweed, the researchers found 10 different anti-fungal
compounds—all different from the ones seen in the first group.
In the DESI-MS technique, a charged stream of polar solvent
is directed at the surface of a sample under study at ambient pressure and
temperature. The spray desorbs molecules, which are then ionized and delivered
to the mass spectrometer for analysis.
“Our collaborative team of researchers from the Department
of Biomedical Engineering and the College
of Sciences has worked within the
Center at Georgia Tech to
better understand the mechanisms of chemical defenses in marine organisms,”
said Fernandez. “This is an example of cross-cutting interdisciplinary research
that characterizes our institute.”
Kubanek is hopeful that other useful compounds will emerge
from the study of signaling compounds in the coral reef community.
“In the natural world, we have seaweed that is making these
molecules and we have fungi that are trying to colonize, infect and perhaps use
the seaweed as a substrate for its own growth,” Kubanek said. “The seaweed uses
these molecules to try to prevent the fungus from doing this, so there is an
interaction between the seaweed and the fungus. These molecules function like
words in a language, communicating between the seaweed and the fungus.”