Bacteria Cells Programmed to Count

Escherichia coli bacteria may be simple organisms, but scientists have now created ones that can count to three.

The advance by scientists from Boston University and the Massachusetts Institute of Technology could lead to environmental or biological sensors that measure toxins and then self-destruct once their job is done.

"We didn't teach the bacteria to count, we programmed them to count," said James Collins, a professor at Boston University and a co-author on the study, which appeared in a recent issue of the journal Science.

"We can use this new ability as a read-out mechanism or control switch."Scientists programmed the E. coli to count by injecting them with a molecule containing two DNA sequences that behave like switches. One switch turns on a minute-counter. The other switch turns on an hour-counter.

The first switch turns on proteins that physically flip a piece of RNA when the E. coli are exposed to sugar over the course of several minutes.

The second switch turns on proteins that flip a small section of DNA over the course of 10 to 15 hours in response to alternating periods of light and dark.

Both switches can flip only three times -- or count to three. Once they reach that number the DNA switches turn on another engineered protein, called a green fluorescent protein, or GFP, which glows green and lets the scientists know that their bacterial timers worked.

This function allows scientists to detect as bacteria count up -- 1, 2, 3, etc. So, the cells could be used to count the number of times it encounters a particular toxin or drug.

Right now cells, bacteria and otherwise, act as one-and-done detectors. As soon as they detect a particular chemical, it triggers a reaction. This can be helpful for detecting the presence of a chemical, but not useful for measuring the number of times a chemical occurs.

But the timer could also act like a time bomb countdown -- 3, 2, 1. At T-minus-zero, the cell could self-destruct, presumably after it's finished its job. Cells already perform a self-annihilation naturally under other circumstances, such as when they begin to divide too quickly or indefinitely, like they do in cancer. The replications add up and trigger apoptosis, or programmed cell death.Scientists used the tools of synthetic biology to program this new ability into E. coli. The genes that encode for the bacterial counters should be relatively easily transferred to other bacteria.

The real trick, according to Stanford University professor Christina Smolke, another scientist using synthetic biology, is to couple the bacterial counters with other systems that make it easier to register the counts.

"The field of synthetic biology is still trying to develop a framework that can take all these components and stick them together to build a fully functional circuit," said Smolke.

"Overall I'm sure that we would want to count to much higher, but this is a start, it demonstrates a foundation, but there are lots of challenges to come as we start linking these models up."