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Scientists teach bacteria to count

May 29, 11:23 AMScience News ExaminerMeg Marquardt
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A colony of E. coli

 Every so often there is a story in science so bizarre that it is difficult to believe.  Many of these stories are coming out of a field known as synthetic biology, a place where scientists are hard at work creating some of the most wickedly cool devices that will be used to combat disease. The most recent design is a duel batch of counting bacteria created in a lab at Boston University.

 Counting bacteria? It is exactly as it sounds.  These bacteria, E. coli as it happens, have been given synthetic gene networks to recognize discrete events, count them, and respond accordingly. In the most basic form, these synthetic gene networks can tell a bacteria to divide three times and then manufacture a fluorescent protein so it can be observed by the researchers. But this is an almost sentient activity, as though the bacteria is playing a game, counting one-Mississippi, two-Mississippi, three-Mississippi before lighting up with a vivid fluorescent “peek-a-boo!”
 
The possibilities of these bacteria are limitless. The above simulation could be applied to the regulation of drug therapies. They could be used to trace cancer, lighting up with a fluorescent protein after a certain number of stimulations by a chemical signal that marks the growth of cancerous cells. And, perhaps most importantly, they can be programmed to self-destruct at a specific time.
 
"The fundamental application is as a safety mechanism," said Professor James J. Collins of Boston University. "If you've engineered an organism to be released into the environment as a biosensor, or you've engineered an organism to go into your body to deliver a therapeutic, in many cases you want to ensure after a certain period of time that the organism is no longer in the environment or your body." [EurekAlert]
 
The team has created two synthetic gene networks by which the bacteria counts, the Riboregulated Transcriptional Cascade (RTC) and the DNA Invertase Cascade (DIC). RTC “counts by starting and stopping transcription and translation – the process by which a gene's instructions are executed – of a series of genes every time an event occurs.” [EurekAlert] After the third interruption, an order is given for the production of a gene that creates a fluorescent protein, allowing scientists to see when the three events have occurred.
 
The second process, DIC, is far more complicated. Instead of simply interrupting transcription, the first event that occurs causes the manufacturing of a protein that “cannibalistically snips its own gene out of the network, flips it over and sticks it back in. Once the gene is backwards, it can no longer be transcribed – but an extra snippet of DNA the researchers attached to its tail acts as a bookmark, showing protein-making machinery where to resume work. Each successive flip-over counts another event, and the fluorescing protein is activated after the third one.” [EurekAlert]
 
Because these synthetic networks function in such different way, the counting bacteria can be used for wildly different applications. RTC works much faster than DIC, meaning they could be used to observe both short- and long-term events that take place in the body.  And since it is in bacteria, scientists could use whole armies for their investigations.
 
Ari Friedland, a graduate student in Collins' lab and a co-author of the paper, said "Consider computing – what does one transistor do for you? Not that much, but if you pack a few thousand onto a chip, then you really have some power. These are fundamental biocomputing devices." [EurekAlert]

 

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