Seeing the shimmer of biology in action  pg. 6

"Being able to image the biological event is critical in studies of drug development.  The advantage here is that bioluminescence imaging can be done in vivo and repeatedly in the same animal, which gets you better data."
E. Duco Jansen, Ph.D., associate professor of Biomedical Engineering at Vanderbilt.
Photo by Anne Rayner
And as with the luminescent tumor cells, the glowing islets offer a model system for evaluating new pharmaceutical interventions. Suppose, Jansen says, that a drug company has a new immunosuppressant drug candidate. That company can use the transplanted islet model and bioluminescence imaging to quickly assess the drug candidate’s efficacy.

“Being able to screen compounds in live animals, with a relatively high throughput readout, is critical for pharmaceutical companies,” Jansen says. “If a drug candidate can be eliminated from the pipeline earlier because of in vivo molecular imaging, that translates into huge cost savings. And likewise, if a candidate can make it to the market sooner, that means millions of dollars of added revenue. Drug companies are very interested in these small animal in vivo molecular imaging approaches.”

Watching the blaze of inflammation

Bioluminescence imaging changed the way Timothy S. Blackwell, M.D., associate professor of Medicine at Vanderbilt, thinks about lung inflammation and injury. In addition to tracking cells and bacterial pathogens, Blackwell’s group has been following gene expression in the context of inflammation.

To do this, the team engineered a “transgenic” mouse that contains the firefly luciferase gene, linked to a stretch of DNA that responds to a transcription factor—a protein that controls the expression of other genes—called NF-kappa-B. When NF-kappa-B is active in cells, it turns on the production of luciferase and the cells light up. NF-kappa-B is an important mediator of inflammatory processes.

In some of their first studies with these transgenic reporter mice, the investigators studied short-term versus long-term infusions of endotoxin, “with the idea of trying to figure out the parameters of inflammatory signaling that lead to lung injury—was it dose, timing, duration, cellular distribution—those sorts of things,” Blackwell says.

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