The National Institutes of Health has awarded Associate Professor James Galagan (BME) and collaborators a grant to study the bacteria that cause tuberculosis. The team’s research efforts could lead to the development of more effective drugs and detection methods to combat the disease.
The research team will use systems biology – an approach that studies the function of a whole organism rather than picking it apart to examine individual genes or proteins — to investigate the inner workings of the bacteria Mycobacterium tuberculosis.
“We’re tackling the problem from an engineering approach, trying to understand how the system works. By taking a comprehensive view of how an organism causes a disease, you’re in a better position to develop drugs, diagnostics and vaccines,” Galagan said. “You have to know your enemy if you want to fight it.”
The National Institute of Allergy and Infectious Disease (NIAID), part of the NIH, awarded the $19.8 million five-year grant to co-principal investigators Galagan and Gary Schoolnik, an infectious disease microbiologist at Stanford University. It is one of four research projects recently awarded a total of $68.7 million from NIAID that will use systems biology approaches to study diseases including salmonella, influenza and severe acute respiratory syndrome (SARS).
“These new projects promise to deepen our fundamental understanding of the complex molecular processes of microbes and their interactions with the host, including how molecular-level events lead to the initiation and progression of disease,” said Anthony S. Fauci, director of NIAID.
“James Galagan is among the best of this new breed of scientists who have one foot in the experimental lab and the other in the world of computer algorithms,” said Professor Mark Klempner, director of BU’s National Emerging Infectious Disease Laboratories (NEIDL) where Galagan has a joint appointment and will perform some of his research. “We now have the ability to generate huge amounts of data in a single experiment and James is among the few people with an idea about how to make sense of that data; with this award he can use that expertise to unravel the secrets of tuberculosis.”
More than 14 million people have been diagnosed with tuberculosis (TB) worldwide, and up to one-third of the world’s population may have a latent, non-symptomatic form of TB infection, according to World Health Organization statistics.
The WHO has had TB in its sights for years, but the disease has proven a tenacious opponent. The organization has seen the number of new cases of TB stabilize and begin to gradually decline since a 2003 peak, according to a 2008 World Health Organization report. However, a blip upward in incidence occurred from 9.1 million new cases in 2005 to 9.2 million in 2006. The disease also killed 1.7 million in 2006. TB is particularly prevalent in Africa and Asia. It is difficult to treat thoroughly because the bacteria have developed drug resistance and patients must take a cocktail of three or four drugs for six to nine months. Diagnosis and treatment need to improve to make a meaningful impact on controlling TB, according to the WHO report.
Clues to better treating TB may come from its ability to exist for years in individuals who may not even know they have it.
“These latent carriers can go on to develop active TB, especially if they become immunocompromised,” Galagan said, which particularly occurs in Africa where TB patients are often co-infected with AIDS. “We think that the state TB is in during latency may be a factor as to why it is so hard to treat. There’s surprisingly little known about this area of TB circuitry.”
Galagan works on computer models that can help understand how TB genes interact with each other and the how metabolic network of the bacterial cell works — revealing how turning a gene turning on or off affects construction of a protein or shutdown of a metabolic pathway. Continually refining their computational models with additional laboratory data, Galagan and Schoolnik hope to learn how TB survives years of latency and which pathways the bacteria turn on or off to transitions from a latent to an active state. Such findings could unveil new drug targets to make TB less likely to develop, or prevent the bacteria from developing resistance to older drugs.
Galagan and Schoolnik will work with a team of several accomplished laboratory and computational TB researchers for the project including investigators at Brigham & Women’s Hospital and the Max Planck Institute in Germany.
Galagan joined the College of Engineering this year as associate professor of biomedical engineering and as an associate director for Systems Biology at the new NEIDL. He comes to BU from Harvard and MIT’s Broad Institute in Cambridge, where he retains his position as the associate director for microbial genome analysis.
“Boston has this amazing landscape for research and has the tremendous resource of the NEIDL. It’s an amazing place to be doing this sort of work because we have all the components in place,” said Galagan.
“James is an astounding example of how collaboration here in our community, between the College of Engineering and the NEIDL, can achieve meaningful scientific advances that address the pressing public health challenges facing the global community,” said Klempner.