Escherichia coli biocomputer solves a maze by sharing work

E. coli thrives in our guts, sometimes to unfortunate effect, and facilitates scientific advances — in DNA, biofuels, and Pfizer’s COVID vaccine, to name a few. Now this multi-talented bacterium has a new trick: it can solve a classic computational maze problem using distributed computing – dividing the necessary computations between different types of genetically modified cells.

This feat is credited with synthetic biology, which aims to outfit biological circuits much like electronic circuits and program cells as easily as computers.

maze experienceThe t is part of what some researchers see as a promising trend in the field: Instead of engineering one type of cell to do all the work, they design multiple types of cells, each with different functions, to get the job done. Working together, these engineered microbes may be able to “compute” and solve problems such as multicellular networks in the wild.

So far, for better or worse, taking full advantage of the design power of biology has eluded and frustrated synthetic biologists. “temper nature Can do this (thinking in the brain), but we “I don’t yet know how to design at this enormous level of complexity using biology,” says Pamela Silver, a synthetic biologist at Harvard University.

study with coli bacteria As maze analysts, led by biophysicist Sangram Bagh at the Sahha Institute of Nuclear Physics in Kolkata, is a simple and fun game problem. But it also serves as a proof of principle for distributed computing between cells, showing how more complex and practical computational problems can be solved in a similar way. If this approach works on larger scales, it could unlock applications for everything from medicine to agriculture to space travel.

“As we move to more complex problems with engineered biological systems, a load distribution like this will be an important capacity to establish,” says David McMillen, a bioengineer at the University of Toronto.

How to build a bacterial maze

get coli bacteria To solve the maze problem involves some ingenuity. Bacteria did not wander into the palace maze of well-manicured hedges. Instead, the bacteria analyzed different maze configurations. Setup: One maze per test tube, with each maze created by a different chemical mixture.

Chemical recipes were extracted from a 2 × 2 grid representing the maze problem. The top left square of the grid is the start of the maze, and the bottom right square is the destination. Each square on the grid can be either an open path or a dead end, resulting in 16 possible mazes.

Bagh and colleagues mathematically translate this problem into a fact table of 1sand 0s, all possible maze configurations are shown. They then assigned these configurations to 16 different combinations of four chemicals. The presence or absence of each chemical corresponds to whether a particular box is open or blocked in the maze.

The team designed multiple sets of coli bacteria Various genetic circuits detected and analyzed these chemicals. Together, the mixed group of bacteria acts as a distributed computer; Each of the different groups of cells performs part of the calculation, chemical information processing, and maze solving.

When conducting the experiment, the researchers put first coli bacteria In 16 test tubes, a different mixture of chemical maze was added into each one, leaving the bacteria to grow. After 48 hours, if the coli bacteria It did not detect any clear path through the maze – that is, if the required chemicals were absent – then the system went dark. If the correct chemical combination is present, the corresponding circuits are ‘turned on’ and the bacteria collectively express fluorescent proteins, in yellow, red, blue or pink, to indicate solutions. “If there’s a pathway or a solution, the bacteria glow,” Bagg says.

Four of the 16 possible maze configurations are shown. The two mazes on the left do not have clear paths from start to destination (due to obstructed/shaded squares), so there is no solution and the system is dark. For the two mazes on the right, there are clear paths (white squares), so coli bacteria Maze solution glows – Bacteria collectively express fluorescent proteins, indicating solutions.

Kathakali Sarkar and Sangram Bagh

What Bug found particularly exciting was that while navigating all 16 mazes, he was coli bacteria It provided physical evidence that only three were solvable. “Calculating this with a mathematical equation is not easy,” says Bagh. “With this experience, you can simply visualize it.”

noble goals

Bagh envisions such a biological computer aiding in cryptography or steganography (the art and science of steganography), which uses mazes to cipher And hide data, respectively. But the implications extend far beyond those applications to the lofty ambitions of synthetic biology.

idea Synthetic Biology It dates back to the 1960s, but the field emerged in concrete terms in the 2000s with the creation of synthetic biological circuits (specifically, a electrical disconnect switch And oscillator) which has made it increasingly possible to program cells to produce desired compounds or to interact intelligently within their environments.

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