E.coli thrives in our stomachs, sometimes to our dismay. It also facilitates scientific advancements--in DNA and biofuels and Pfizer's covid vaccination, just to name a few. This multitalented bacterium now has a new trick. It can solve the classic computational maze problem by using distributed computing, which divides up the calculations between different genetically engineered cells.
This is synthetic biology's credit for this remarkable feat. It aims to program cells and rig biological circuitry as easy as computers.
Researchers consider the maze experiment part of a promising trend in the field. Instead of focusing on one type of cell, they create multiple cells with different functions to accomplish the same task. These engineered microbes may be able to work together and solve problems in a way that is more similar to multicellular networks found in nature.
Synthetic biologists have been frustrated and unable to harness biology's design power. Pamela Silver, a Harvard synthetic biologist, says that nature can do it (think of a brain), but that we don't know how to design biology at such an overwhelming complexity.
It is a fun and simple toy problem that Sangram Bagh, a biophysicist at the Saha Institute of Nuclear Physics, Kolkata, has conducted with E. coli. It also serves to demonstrate how distributed computing among cells can solve more difficult and practical computational problems in a similar manner. This approach could be used to unlock many applications, including space travel and pharmaceuticals.
David McMillen, a University of Toronto bioengineer, says, "As we progress into solving more complicated problems with engineered biologic systems, spreading out load like this will be an important capability to establish."
How to create a bacterial maze
It took some creativity to get E. coli into the maze. The bacteria did not wander through a maze of well-pruned hedges. Instead, the bacteria examined different maze configurations. Each maze was created by a different chemical combination.
A 2 x 2-grid representing the maze problem was used to extract the chemical recipes. The maze's start point is in the grid's top left corner. The destination is in the bottom right corner. There are 16 possible mazes for each square of the grid. Each square can be an open path or blocked.
Bagh and his coworkers mathematically converted this problem into a truthtable composed of 1s or 0s. This table shows all possible maze configurations. They then mapped the configurations onto 16 different combinations of four chemicals. Each chemical's presence or absence determines whether a square is blocked or open in the maze.
Multiple sets of E. coli were engineered by the team with different genetic circuits to detect and analyze those chemicals. The mixed bacteria population functions as a distributed computer. Each set of cells does part of the computation and processes the chemical information.
The researchers started the experiment by putting the E. coli into 16 test tubes. Next, they added a chemical-maze combination to each tube and allowed the bacteria grow. If the E.coli could not find a clear path through the maze, the system would remain dark for 48 hours. The correct chemical combination turned on the circuits and bacteria collectively produced fluorescent proteins in yellow, red or blue to indicate the solution. Bagh says, "If there's a path, there's a solution, then the bacteria glow."
These are four of the 16 possible maze configurations. Due to obstructed/shaded areas, the mazes on the left don't have clear paths to their destination. The system is also dark. The mazes to the right have clear paths (white squares), so E.coli maze solver glows. This is because the bacteria collectively produce fluorescent proteins that indicate the solutions. KATHAKALI SARKAR and SANGRAM BAGH
Bagh was particularly impressed by the fact that, after churning through 16 mazes of E. coli, he could prove that only three were solvable. Bagh said that it was difficult to calculate this using a mathematical equation. This experiment will help you visualize it.
High goals
Bagh imagines such a computer as a biological computer that can be used to help in cryptography and steganography, which are the art and science behind hiding information. They use mazes to encrypt or conceal data. The implications go beyond synthetic biology's higher ambitions.
Although synthetic biology was first proposed in the 1960s, it became a reality with the invention of synthetic biological circuits (specifically a toggle switch, an oscillator), which made it possible to program cells to make desired compounds and react intelligently within their environment.
