Escherichia coli biocomputer solves the maze through shared work

Escherichia coli thrives in our intestines and sometimes has unfortunate effects. It promotes scientific progress-DNA, biofuels and Pfizer’s new crown vaccine, to name a few. Now, this versatile bacteria has a new trick: it can use distributed computing to solve the classic computational maze problem-dividing the necessary calculations between different types of genetically engineered cells.

This ingenious feat is attributed to synthetic biology, which aims to assemble biological circuits like electronic circuits and program cells as easily as computers.

Maze experimentThis is part of what some researchers think is a promising direction in the field: instead of designing a single type of cell to do all the work, they design multiple types of cells, each with a different function, to do the job. Through collaborative work, these modified microorganisms may be able to “calculate” and solve problems that are more like multicellular networks in the wild.

So far, for better or worse, synthetic biologists have failed to make full use of the design capabilities of biology, and it has also made them feel frustrated. “nature It can be done (think about the brain), but US I don’t know how to use biology to design at such a complex level,” said Pamela Silver, a synthetic biologist at Harvard University.

The research and Escherichia coli The maze solver led by biophysicist Sangram Bagh of the Saha Institute of Nuclear Physics in Calcutta is a simple and interesting toy problem. But it can also be used as a proof of principle for distributed computing between units, showing how to solve more complex and practical computing problems in a similar way. If this method works on a larger scale, it can unlock all applications from pharmaceuticals to agriculture to space travel.

“As we begin to use engineered biological systems to solve more complex problems, distributing loads like this will become an important capability,” said David Macmillan, a bioengineer at the University of Toronto.

How to make a bacterial maze

get Escherichia coli Solving the maze problem requires some ingenuity. Bacteria did not wander in the palace labyrinth of carefully manicured hedges. Instead, bacteria analyzed various maze configurations. Setting: One maze for each test tube, each maze is generated by a different chemical mixture.

The chemical formula is abstracted from the 2 × 2 grid that represents the maze problem. The square in the upper left corner of the grid is the starting point of the maze, and the square in the lower right corner is the destination. Each square on the grid can be an open path or blocked, resulting in 16 possible mazes.

Bagh and his colleagues mathematically transformed this problem into a truth table 1sand 0s, display all possible maze configurations. Then they mapped these configurations to 16 different mixtures of four chemicals. The presence or absence of each chemical substance corresponds to whether a specific square in the maze is open or closed.

The team designed multiple sets Escherichia coli Different gene circuits are used to detect and analyze these chemicals. The mixed populations of bacteria act together as a distributed computer; each of the different cell groups performs partial calculations, processes chemical information, and solves maze problems.

When conducting experiments, the researchers first Escherichia coli In 16 test tubes, add a different chemical maze mixture to each test tube to allow bacteria to continue to grow. After 48 hours, if Escherichia coli No clear path through the maze is detected—that is, if there are no necessary chemicals—the system will remain dark. If the correct chemical combination exists, the corresponding circuit will be “turned on” and the bacteria will collectively express yellow, red, blue, or pink fluorescent proteins to indicate a solution. “If there is a path and a solution, the bacteria will glow,” Bagh said.

Four of the 16 possible maze configurations are shown. The two mazes on the left do not have a clear path from the start to the end (due to the block being blocked/shaded), so there is no solution and the system is dark.For the two mazes on the right, there are clear paths (white squares), so Escherichia coli The maze solver glows-bacteria co-express fluorescent proteins to indicate the solution.


What Bagh found particularly exciting is that when traversing all 16 mazes, Escherichia coli Provided physical evidence that only three are solvable. “Calculating this with mathematical equations is not easy,” Bagh said. “Through this experiment, you can visualize it very simply.”

Ambitious goal

Bagh envisions such a biological computer to contribute to cryptography or steganography (the art and science of hiding information), which uses a maze to encryption with hide Data, respectively. But its impact is not limited to these applications, it also involves higher ambitions in synthetic biology.

Thoughts Synthetic biology Can be traced back to the 1960s, but the field was developed with synthetic biological circuits in 2000 (especially Toggle Switches with Oscillator) This makes it more and more possible to program cells to produce desired compounds or to react intelligently in their environment.

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