Graphic Credit: Bryan Christie Design

 

MIT Technology Review, August 25, 2010  —  Mere months after Kyoto University researchers announced in 2007 that they had discovered how to turn skin cells into induced pluripotent stem cells (iPS cells), Jacob Hanna used these new types of cells to cure mice of sickle-cell anemia, in which a genetic defect causes bone marrow to make defective red blood cells. Hanna, a fellow at the Whitehead Institute, took skin cells from a diseased mouse and reprogrammed them create iPS cells, which behave like embryonic stem cells, readily turning into any cell type in the body. He then corrected the sickle-cell genetic defect and prodded the iPS cells to develop into the type of marrow stem cell that manufactures a mouse’s blood cells. These healthy cells were transplanted back into the mouse, whose immune system accepted them as the animal’s own tissue. The treated mouse began producing healthy red blood cells on its own.

Hanna’s work was a turning point for iPS research, says George Daley, director of the Stem Cell Transplantation Program at Boston’s Children’s Hospital and a professor at Harvard Medical School: “It was a beautiful demonstration of a mouse model of a human disease, and really demonstrated the potential of iPS cells.”

Before iPS cells can be used to treat diseases such as sickle-cell anemia in humans, a lot of work has to be done to make sure they won’t cause adverse side effects and to improve the efficiency of deriving them from skin cells. Hanna is now developing simulations to understand what happens when cells are reprogrammed, and he’s searching for new types of human stem cells that could be easier to turn into adult cells.–Nidhi Subbaraman

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. Graphic Credit: Bryan Christie Design

MIT Technnology Review, August 25, 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, age 29, 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

Visit Dr.Timothy Lu’s lab to see how he destroys biofilms using engineered viruses.