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Siebel Scholar Timothy Lu Named Top Innovator Under 35

ARTICLE BY: Carl Zimmer

Technology Review, TR35

October 15th 2010

At Harvard Medical School, many of Timothy Lu's patients were being attacked by carpets of microbial goo. They had "really bad infections," Lu says. "Patients with cystic fibrosis, people getting infections in their catheters. All caused by biofilms."


Lu, who is now an assistant professor at MIT, began researching how to destroy biofilms. But unlike those who had previously attacked the problem, he took advantage of the new tools of synthetic biology. He engineered a type of virus, known as a phage, to destroy biofilms and sabotage their defenses against antibiotics. His accomplishment could produce synthetic biology's first big commercial success by attacking the biofilms that infest industrial equipment.


When bacteria settle on a surface, they spew out molecules that bind the entire population together and cover it in a protective shield. Bacteria in these biofilms are up to 500 times more resistant to antibiotics than free-floating microbes are. Normally, viruses have a hard time penetrating the dense layers of a biofilm. But Lu stumbled across an enzyme produced by oral bacteria that can break up biofilms. He inserted the gene for the enzyme into a phage called T7 so that when the virus infects a microbe, it makes as much of the enzyme as possible.


When the engineered T7 is unleashed on a biofilm, it invades the top layer of bacteria. These bacteria soon burst open, spilling out enzymes and new phages. Aided by the enzyme, the viruses then penetrate the next layer of bacteria, repeating the cycle until the biofilm is destroyed. Lu and his colleagues have also found other ways to turn phages into effective weapons against biofilms, such as creating versions that can shut down the genes that bacteria use to defend themselves against antibiotics.


Last year Lu cofounded Novophage (now called Ascendia Biotechnology) to develop commercial applications for the phages. The company is initially concentrating on biofilms that Lu says can corrode water pipes and block heat transfer in heating and cooling systems, decreasing energy efficiency by up to 80 percent. Conventional industrial attempts to deal with biofilms have involved scrubbing pipes, applying chemicals, or exposing the films to ultraviolet light, but these treatments are not very effective, can damage piping, and are toxic to humans and the environment. A small injection of phages into a water pipe, however, could clean an entire system, with the phages replicating themselves as they consume the biofilm. --Carl Zimmer


The bane of biofilms: Bacteria bound together in a protective matrix tend to resist viral attack. But Lu's virus produces an enzyme that breaks up these biofilms. When it infects the bacteria on the biofilm's surface, they burst and release viruses that infect those underneath, soon exposing even deeply embedded bacteria to infection.
Credit: Bryan Christie Design


Read the original article, including a video of Timothy's lab: