E. coli Thrives in our bowels, sometimes with unfortunate effects, and enables scientific advances – in DNA, biofuels, and Pfizer’s Covid vaccine, to name a few. Now the multi-talented bacterium has a new trick: it can solve a classic computational labyrinth problem with distributed computing – by dividing the necessary computations into different types of genetically modified cells.
This great achievement is due to synthetic biology, which aims to build biological circuits similar to electronic circuits and to program cells as easily as computers.
The maze experiment is part of what some researchers see as a promising direction in the field: instead of developing a single type of cell to do all the work, they are designing multiple types of cells, each with different functions, to do the job. Working together, these engineered microbes may be able to “compute” and solve problems that are more like multicellular networks in the wild.
So far it has escaped synthetic biologists, for better or worse, and frustrated to fully exploit the creative power of biology. “nature can do this (think of a brain) but weather don’t yet know how to use biology to create such an overwhelming level of complexity, ”says Pamela Silver, synthetic biologist at Harvard.
The study with E. coliThe labyrinth solvers, directed by the biophysicist Sangram Bagh at the Saha Institute of Nuclear Physics in Kolkata, is a simple and entertaining “toy” problem. But it also serves as a proof of principle for distributed computing between cells and shows how more complex and practical computing problems could be solved in a similar way. If this approach works on a larger scale, it could open up applications that range from pharmaceuticals to agriculture to aerospace.
“If we are solving more complex problems with artificial biological systems, such load distribution will be an important skill to establish,” says David McMillen, a bio-engineer at the University of Toronto.
How to build a bacteria maze
Receive E. coliIt took some ingenuity to solve the maze problem. The bacteria did not migrate through a palace maze of well-cut hedges. Rather, the bacteria analyzed different labyrinth configurations. The structure: one labyrinth per test tube, each labyrinth being created by a different chemical preparation.
The chemical recipes were abstracted from a 2 × 2 grid that depicts the labyrinth 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 blocked path, making 16 possible mazes.
Bagh and his colleagues mathematically translated this problem into a truth table made up of 1 s and 0 s showing all possible maze configurations. Then they mapped these configurations onto 16 different mixtures of four chemicals. The presence or absence of each chemical corresponds to whether a particular square in the maze is open or blocked.
The team developed several sets of E. coli with various genetic circuits that discovered and analyzed these chemicals. Together, the mixed bacterial population functions as a distributed computer; Each of the different cell groups performs part of the calculation, processes the chemical information and solves the maze.
When conducting the experiment, the researchers first identified the E. coli in 16 test tubes, added a different chemical maze preparation to each and let the bacteria grow. After 48 hours if the E. coliDidn’t find a clear path through the maze – that is, if the required chemicals weren’t there – the system remained dark. When the right combination of chemicals was in place, appropriate circuits were “turned on” and the bacteria collectively expressed fluorescent proteins in yellow, red, blue, or pink to indicate solutions. “If there is a way, a solution, the bacteria glow,” says Bagh.
Bagh found it particularly exciting that when rummaging through all 16 mazes theE. coliprovided physical evidence that only three were solvable. “Calculating this with a mathematical equation is not easy,” he says. “With this experiment you can easily visualize it.”
Bagh envisions a biological computer that aids in cryptography, or steganography (the art and science of hiding information) that uses mazes to encrypt and hide data, respectively. But the implications extend beyond these applications to the higher ambitions of synthetic biology.
The idea of synthetic biology dates back to the 1960s, but the field concretely emerged in 2000 with the creation of synthetic biological circuitry (specifically a toggle switch and an oscillator) that increasingly made it possible to program cells to produce or create desired compounds their surroundings react intelligently.