A Brigham Young University researcher is melding his expertise in evolutionary biology with physicians at medical powerhouse Johns Hopkins University to track the transmittal of a stubborn infectious disease.
The National Institutes of Health awarded the collaborative team $2.6 million over five years to apply new methods to the study of gonorrhea, which is treatable by simple antibiotics but persists in urban centers such as Hopkins' home, Baltimore.
Instead of the traditional approach to reconstructing the spread of sexually transmitted diseases -- interviews with patients about their sexual histories -- the new study seeks genetic clues embedded in the bacteria themselves that could tip off doctors to the concentrations of particularly potent strains and possibilities for vaccination.
"Instead of examining patients and gauging symptoms, we're examining the bacteria that are causing their symptoms," said Keith Crandall, a BYU biology professor. "We can overlay the genetic data we develop with geographic information about the patients and track the spread of the disease."
Using computer programs his research teams have developed to study the evolution of the virus that causes AIDS, Crandall will analyze a dozen genes from each sample of the germ that causes gonorrhea. He and his counterparts at Johns Hopkins will look for differences in the genetic sequences in order to identify patterns of transmission and possible reasons for the continued success of the disease.
With some 10,000 samples gathered over 20 years by Jonathan Zenilman, a Johns Hopkins epidemiologist, the project will comprise one of the largest population genetics studies ever undertaken. The DNA sequencing is supervised by Raphael Viscidi, the study's principal investigator and a Hopkins researcher, who e-mails to Crandall long lists of letters that symbolize the bacteria genes.
The BYU biologist then runs the data through complex computer programs he developed, which have been recognized in "Science," "Nature" and other journals, to account for the changes of organisms' genetic codes inherent in the reproductive process.
The research team is particularly interested in testing a theory that a group of people who are more resistant to common strains of the gonorrhea bacteria may be harboring more genetically diverse and therefore more potent strains, which are more effective at infecting people outside this core group.
"They're individuals who maintain the epidemic in the population by frequently becoming infected, and then they occasionally spread the infection to other individuals who are considered part of peripheral populations," said Viscidi.
Once core clusters are identified, interventions could possibly be designed to be more effective at reaching these key groups.
"A long-term focus of this grant is to see whether the genetic information can allow us to understand the spread of the organism through the population," said Viscidi. "If we're able to do that, then we can devise public health strategies for interrupting epidemics."
Another aspect of the new study is the incorporation of a new approach to comparing DNA sequences that puts many more genes under the scientists' figurative microscope than previous methods. Crandall's team selects bigger chunks of the bacterium's genome to examine.
BYU students working on the project, like Aaron Madsen, who has been supported by grants from the university and its Cancer Research Center designed to encourage undergraduate research, are seeking to standardize which patches of DNA are analyzed. Therefore, scientists studying similar bacteria, such as the one that causes meningitis, will also be able to benefit from their results.
Additionally, Crandall plans to study a particular gene in the gonorrhea bacteria that interacts with the human immune system. The gene is key for vaccine development, a process in which Crandall is already involved through his work with the California company VaxGen, which is in the final stage of testing a preventive HIV/AIDS vaccine.
"Our first priority is to understand how gonorrhea spreads through a community," said Crandall. "We also want to know how this bacterial population is evolving drug resistance so that down the road we can contribute to possible new treatments and vaccines."
