GRANITE program to aid in development of new TB fighting methods

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A Rutgers-Camden professor is using his expertise in computer science to aid in the development of new methods to fight tuberculosis.

Desmond Lun, an associate professor of computer science, has received $36,589 from a Lockheed Martin contract administered by the National Institutes of Health for his work with GRANITE (Genetic Regulatory Analysis of Networks Investigational Tool Environment), a software platform designed to simulate the behavior of living cells.

The role of Lun's lab in the funded project is to use the GRANITE program to make predictions about the behavior of Mycobacterium tuberculosis, the bacterium that causes tuberculosis.

Tuberculosis bacteria usually attack the lungs, but also can attack other parts of the body such as the kidneys, spine, and brain. If not treated properly, tuberculosis can be fatal, according to the Centers for Disease Control and prevention.

"There are drugs that fight tuberculosis, but as is often the case with bacterial diseases, it develops immunities to these drugs," Lun says. "There's quite a search going on for new drugs and researchers are now looking at an area of the organism known as central metabolism. We want to disrupt the process of how the organism takes the nutrients of its environment, breaks them down, and uses them to grow."

Lun is using the GRANITE program, developed by defense contractor Lockheed Martin under the auspices of the Office of Cyber Infrastructure and Computational Biology at NIAID/NIH, to simulate disruption of the bacteria's metabolism.

"We're looking for things that may kill the organism," he says.

The computer simulation can give researchers answers and new insight into the process much faster than it would take to grow a tuberculosis bacteria culture and test various ways to disrupt its metabolism.

"Doing these experiments is very difficult and you want to test potential targets quickly, which isn't possible," Lun says. "Tuberculosis is a very slow-growing organism. It takes weeks to months to grow a culture, so if you want to test a genetic change, then that's the timeframe you're looking at. By using a computer simulation, you can pick out, say, the 10 most promising ways out of 100 to alter the organism. That saves a lot of time and money."

Lun, who has also researched how to alter the genetic makeup of E. coli to produce biodiesel fuel derived from fatty acids, says predicting how an organism behaves with a computer simulation can also be applied to other microbes.

The tuberculosis research is part of a much larger endeavor to capture the rules that govern how biological systems behave.

"This is only the first step," Lun says. "Who knows where it will go? It's a very exciting project to be a part of."

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