Cells that Like to Count

A pair of engineers at MIT and Boston University have built a series of cascading molecular pathways into cells that allow them to count specific events, which one day might include the number of times a cell divides or exposure to an external compound. They have already engineered two different counters, both relying on the same principle, a molecular chain in which the occurrence of one event is directly dependent on the occurrence of the event before it. Their first counter uses different RNA polymerases, each coded in a series of genes. A stimulus, say a sugar molecule, initiates the production of the first polymerase, which controls the transcription of the next RNA polymerase, which will transcribe the next, assuming the same stimulus appears again. This process is repeated until, at the end of it all, some sort of finish-line indicator like a fluorescent protein would tell that the chain is done. Currently, the team has only built in the ability to count three events, but the number of counts from this RNA polymerase method is only limited by the number of bacterial RNA polymerases in existence. Their second counter uses a DNA invertase enzyme that, when triggered, cuts out a section of DNA, flips it, and reinserts it, thereby ending its own transcription and preparing for the next DNA invertase to be activated.
One practical use of this technology might be to appease those concerned about creating genetically modified cells. A cell, for example, could be programmed to self-destruct by means of this counting system, after say, 100 divisions.
From the MIT News Room:

The team developed two types of cellular counters, both described in the May 29 issue of Science. Though the cellular circuits resemble computer circuits, the researchers are not trying to create tiny living computers…
“Our goal is to build simple design tools that perform some aspect of cellular function,” said Lu…
Because it tracks a specific sequence of stimuli, such a counter could be useful for studying the unfolding of events that occur during embryonic development, said Lu.
Other potential applications include programming cells to act as environmental sensors for pollutants such as arsenic. Engineers would also be able to specify the length of time an input needs to be present to be counted, and the length of time that can fall between two inputs so they are counted as two events instead of one.
They could also design the cells to die after a certain number of cell divisions or night-day cycles.
“There’s a lot of concern about engineered organisms — if you put them in the environment, what will happen?” said Collins, who is also a Howard Hughes Medical Institute investigator. These counters “could serve as a programmed expiration date for engineered organisms.”

Link: Engineered circuits can count cellular events
Image: Graphic showing the sort of cascading dependent pathway that allows the cells to count.