The winner of the 2012 competition for the best collaborative publication was announced on May 7, as part of the lead-up to the Spring Research Festival sponsored by the National Interagency Confederation for Biological Research (NICBR) and the National Cancer Institute at Frederick on May 8 and 9.
By Nancy Parrish, Staff Writer
The winning paper was selected from five entries for best publication resulting from collaborative research between
two or more NICBR partners based on the Fort Detrick campus. The partner agencies include the U.S. Army Medical
Research and Materiel Command and U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID); National
Institute of Allergy and Infectious Diseases; National Cancer Institute; U.S. Department of Agriculture; National
Biodefense Analysis and Countermeasures Center; Centers for Disease Control and Prevention; Naval Medical Research
Center; and U.S. Food and Drug Administration.
The paper focuses on a potential therapeutic agent against Staphylococcal enterotoxin B (SEB), a deadly toxin
by Staphylococcus aureus, which has been associated with severe—even fatal—food poisoning. Exposure to SEB, according
to the paper, can trigger an exaggerated immune system response, often leading to toxic shock syndrome associated
with organ failure and death.
The study was the result of a collaboration that began at the 2010 Spring Research Festival, when David Waugh,
Ph.D., senior investigator, Macromolecular Crystallography Laboratory, NCI at Frederick, opened discussions with
Kamal Saikh, Ph.D. principal investigator, Integrated Toxicology Division, USAMRIID, about the research presented
in Saikh’s poster. Waugh said that he realized “Saikh’s research could be enhanced and extended by employing biophysical
methods such as NMR [nuclear magnetic resonance] and X-ray crystallography to study the interactions of small
molecules with proteins that propagate signals in the innate immune response pathway.”
Those discussions led to research that focused on MyD88, a gene involved in the body’s immune response. The researchers
produced a synthetic compound based on MyD88 that was introduced into mice either before or after SEB exposure.
The effect was to reduce the level of immune response to the toxin and, in fact, protected the mice from getting
toxic shock syndrome.
Waugh’s laboratory, which focuses on high-throughput protein expression and purification, and structural biology,
produced the recombinant MyD88 protein for the studies, including samples enriched with the stable isotope 15N
for the NMR experiments conducted by the laboratory of Julius Rebeck, Ph.D., at The Skaggs Institute for Chemical
Biology, The Scripps Research Institute. Sun Ping, Ph.D., a visiting fellow in Waugh’s lab did the hands-on work
for the project.
Saikh’s laboratory led the investigation.
Both researchers believe that the promising results of their study would not have been possible without the collaboration
fostered by NICBR. “It enabled us to make an impact on the rapidly developing field of innate immunity, where
complex signaling cascades are being uncovered,” Waugh said. This type of research “is not something we would
normally do in my lab,” he added.
Saikh felt the collaboration enabled his research to progress toward developing therapeutic agents to treat SEB.
“Currently, no licensed treatments are available for SEB intoxication,” he said. “Our work, combined with the
work of Dr. Waugh’s group, enabled us to identify and validate a target-based potential lead candidate for the
treatment of SEB.”
Waugh appreciates the chance to collaborate with other NICBR agencies. These collaborations, he said, present “an
opportunity to participate in biomedical research that is not being conducted at my own institute, but which interests
me nonetheless.” Further, he said that “in an environment in which resources for biomedical research in my own
institute (NCI) have been reduced to an unprecedented low point, and with additional budget cuts all but certain,
collaborations like this one are essential for us to be able to continue to conduct meaningful scientific research.”
Other interagency collaborations his laboratory is involved in include studies of Venezuelan equine encephalitis
virus and human protein tyrosine phosphatases involved in cancer and host response to infectious agents. Both
studies are collaborations with USAMRIID.
View the full publication:
Therapeutic Inhibition of Pro-Inflammatory Signaling and Toxicity to Staphylococcal Enterotoxin B by a Synthetic Dimeric BB-Loop Mimetic of MyD88