At this moment, the naturally occurring biological weapon, anthrax, lies dormant all over the world in the form of spores, waiting for the right time and an unlucky host to strike. Within hours of infecting a foraging herbivore or its human handler, the spores spring to life and begin a frenzy of replication and proliferation, wreaking intercellular havoc, most likely resulting in death. And at the University’s newly created Biodefense Proteomics Research Center, researcher Phillip Hanna is looking for ways to disable the bacterium at these earliest stages of infection.
The center, directed by Hanna, was created with a $5.9 million grant last month, from the National Institutes of Allergy and Infectious Disease, part of the National Institutes of Health. Of the seven new centers created by NIAID, the University, along with the Scripps Research Institute in La Jolla, Calif., is charged with investigating the deadly anthrax pathogen.
The goals of this center will be twofold: To discover what Hanna calls the “choke points” – or critical moments – in the early development of Bacillus anthracis, the spore-forming bacterium that causes anthrax, and to disseminate this information efficiently to other scientists studying the pathogen.
Nicholas Bergman, co-director of the center and faculty member in the University’s department of bioinformatics, will principally be involved in mining the information for “interesting patterns,” which will be no easy task.
“Our research should really increase the data we have available,” Bergman said. Emphasizing the cooperative nature of studying the deadly bacterium, Bergman’s goal will be to analyze the data and make it “available to others in academia and industry who are better able to take individual leads to the next step.”
The University will be taking a unique approach to understanding the biology of anthrax. “The combination of proteomics and genomics, applied together toward the same problem, has allowed us to take some huge strides toward understanding … big processes like spore formation,” Bergman said. “(The University) plays a pretty dominant role in anthrax research nationwide.”
While genomics focuses on sequencing the genome, or cataloguing the genetic code of an organism, proteomics is the considerably messier study of proteins and their action in cells. While genes code for amino acids that become the building blocks of proteins, the proteins themselves combine and recombine into a dizzying array of possibilities.
Hanna said, defining which of the about 6,000 anthrax genes give the bacterium such lethal success will enable researchers to find “specific molecules … for vaccines, antibiotic drugs and diagnostics.”
Hanna is working on a hunch: That figuring out which proteins are active in the earliest stages of anthrax infection will allow researchers to shut those mechanisms down and thereby stop the budding spores dead in their tracks.
“We hypothesize the best time to intervene medically is the early, establishment stages of anthrax,” Hanna said.
Also under investigation is how the long-dormant anthrax spore can reanimate itself so quickly once inside a suitable host. In a matter of hours, the germ gathers nutrients, produces toxins and starts manufacturing proteins that enable it to elude the body’s immune mechanisms. According to the Centers for Disease Control and Prevention, anthrax spores are found naturally in soil, most commonly in agricultural and developing regions of the world.
Earlier this year, however, Hanna and his team took a sample of soil from a bank on the Huron River back to his lab and found that anthrax was able to go through complete growth cycles in it.
Hanna emphasized that “this does not mean this actually happens in nature, where the competition for food is fierce” as opposed to the ideal growing conditions in the lab, although “there is the possibility.”
In the lab, Hanna works with a less harmful or defanged version of B. anthracis called the Sterne strain, a live animal vaccine approved by the U.S. Department of Agriculture. Two large, circular chunks of DNA called plasmids are needed by the bacteria to remain virulent. One is the source of its toxicity and the other creates a “slimy outer coat covering the growing anthrax” and protects it from immune-system attack, Hanna said. The Sterne strain lacks the plasmid necessary to produce the outer coating.
In addition to working with a safer strain of anthrax, Hanna scrupulously maintains safe conditions in working with the lethal pathogen. “We will perform no work that we cannot do safely,” Hanna said. Oversight from the CDC, NIH, the University’s Biosafety Committee, the Department of Occupational Safety and Environmental Health, and the Department of Public Safety, all abide by the same standards.
Outside of the lab, however, “the problem is that there are so many unguarded, natural sources where someone could get B. anthracis,” Bergman said. The ultimate goal is to develop an effective vaccine to prevent anthrax outbreaks, and then to develop drugs to treat the infections that do occur.
Said Bergman, “I’m not sure anthrax will ever disappear as a threat, but we can certainly make it easier to deal with.”