You’ve probably seen this in recent news: a group of Japanese scientists have engineered bacteria that can solve a 4×4 grid version of Sudoku.  What most of the on-line articles don’t mention is that this group consisted of undergraduate students from the University of Tokyo.  This project was their entry in the International Genetically Engineered Machine (iGEM) competition, which challenges to students to make biological systems that operate inside living cells.

Escherichia coli can adopt unique characteristics through mutation or incorporation of genetic material from another organism (the existence of different strains is why E.coli can both harmlessly live in your intestine and give you food poisoning).  The UT-Tokyo team engineered 16 different strains of E.coli that produce colonies of 4 possible colors; these colors, which are the result of fluorescent proteins being produced, are the equivalent to the numbers 1-4 on a 4×4 Sudoku grid.  The following clip explains the biochemistry behind making the Sudoku-solving E.coli.

Confused by all the jargon? Let me try to explain with an analogy. Each of the 16 strains has DNA that codes for all of the 4 fluorescent proteins that express red, yellow, green, or blue. This is the equivalent of how each square in a 4×4 puzzle can be any of number from 1-4.

However, Suduoku puzzles already have some of the numbers written in. Likewise, the team has prepared a few E.coli strains that already express a single color (they’re known as being differentiated).  These bacteria send out signals in the form of enzymes called RNA recombinases that tell the nearby undifferentiated bacteria what color protein they can NOT produce. This is done through viruses that have been engineered into the differentiated E.coli. The team collects the virus and uses them to infect the “detection” E.coli.

The RNA recombinases are like the rules of Sudoku, and the detection E.coli are like the answers you write in (versus the supplied answers/differentiated E.coli. When you’re solving Sudoku, you see the pre-assigned numbers and known that the rules prohibit the other boxes in the same grid, row, and column to be that number. The viruses infect the detection bacteria on plate, sending the RNA recombinases to do their job. The enzymes cut out the portion of the RNA “message” for three of the proteins coded by the DNA (basic biology lesson: DNA codes RNA, which codes protein that is expressed by the organism).

Think of this as a process of elimination. Once the message for three of proteins have been removed, there is another message that tells the bacteria to express the remaining fluorescent protein. This happens right before your eyes, as different colored E.coli colonies grow on a plate that has the 4×4 grid mapped out.

Listening to: “Promise on Christmas” by Nana Mizuki