Catching Lightning in a Petri Dish

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What time is it? Maybe the E. coli in your intestines will tell you some day. Scientists at the University of California at San Diego have created a "clock" made of genetically engineered bacteria. The bacteria rhythmically flash blue light like a bulb on a string of Christmas tree lights. While stopwatches in your GI tract may never happen (which might be a good thing), artificial biological oscillators like the light show in a Petri dish in San Diego may be used in the future to make time-sensitive drug delivery devices and to help understand many of the natural timepieces that underlie both normal physiology and some diseases.

As reported last week in Nature and The New Scientist, the San Diego team built their biochemical clock by placing three genes under control of the chemical AHL.  These genes coded for three proteins- one that makes more AHL, a blue fluorescent protein, and a protein that acts as a "circuit breaker," shutting off production of the other genes and destroying AHL.

As the bacterial cells grew, they slowly secreted more AHL, driving the production of these three genes. At first, levels of the AHL-producing protein increased rapidly, leading to a vicious cycle of AHL production. However, this also increased expression of the circuit breaker protein, which blocked the creation of more AHL and destroyed the AHL already in the cell. Once all of the circuit breaker protein was gone, AHL levels could increase, starting the cycle all over again. Production of the blue fluorescent protein was linked to the level of AHL in the cell, so the blue glow of the cells rose and fell in synch with the AHL cycle.

Although it may seem like having a microscope slide full of bacteria blinking blue wouldn't have any use besides making lab life more colorful for the San Diego team, this study represents a major advance for genetic engineering and may have practical benefits. While genetically modified bacteria have been made to flash on and off, no other study has managed to synchronize the behavior of a whole population of cells. Synched-up groups of cells might be used implants for diabetics to mimic the way the pancreas periodically pumps insulin. Other biological systems, perhaps most notably the nervous system, depend on rhythmic behavior, and building artificial biological clocks may help us understand the function and pathology of natural clocks.

- blog authored by John Froberg

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