Cell-based biocomputing is a novel technique that uses cellular processes to perform computations. Such micron-scale biocomputers could overcome many of the energy, cost and technological limitations of conventional microprocessor-based computers, but the technology is still very much in its infancy. One of the key challenges is the creation of cell-based systems that can solve complex computational problems.
Now a research team from the Saha Institute of Nuclear Physics in India has used genetically modified bacteria to create a cell-based biocomputer with problem-solving capabilities. The researchers created 14 engineered bacterial cells, each of which functioned as a modular and configurable system. They demonstrated that by mixing and matching appropriate modules, the resulting multicellular system could solve nine yes/no computational decision problems and one optimization problem.
The cellular system, described in Nature Chemical Biology, can identify prime numbers, check whether a given letter is a vowel, and even determine the maximum number of pizza or pie slices obtained from a specific number of straight cuts. Here, senior author Sangram Bagh explains the study’s aims and findings.
How does cell-based computing work?
Living cells use computation to carry out biological tasks. For instance, our brain’s neurons communicate and compute to make decisions; and in the event of an external attack, our immune cells collaborate, compute and make judgements. The development of synthetic biology opens up new avenues for engineering live cells to carry out human-designed computation.
The fusion of biology and computer science has resulted in the development of living cell-based biocomputers to solve computational problems. Here, living cells are engineered to use as circuits and components to build biocomputers. Lately, researchers have been manipulating living cells to find solutions for maze and graph colouring puzzles.
Why did you employ bacteria to perform the computations?
Bacteria are single-cell organisms, 2–5 µm in size, with fast replication times (about 30 min). They can survive in many conditions and require minimum energy, thus they provide an ideal chassis for building micron-scale computer technology. We chose to use Escherichia coli, as it has been studied in detail and is easy to manipulate, making it a logical choice to build a biocomputer.
How did you engineer the bacteria to solve problems?
We built synthetic gene regulatory networks in bacteria in such a way that each bacterium worked as an artificial neuro-synapse. In this way, 14 genetically engineered bacteria were created, each acting like an artificial neuron, which we named “bactoneurons”. When these bactoneurons are mixed in a liquid culture in a test tube, they create an artificial neural network that can solve computational problems. The “LEGO-like” system incorporates 14 engineered cells (the “LEGO blocks”) that you can mix and match to build one of 12 specific problem solvers on demand.
How do the bacteria report their answers?
We pose problems to the bacteria in a chemical space using a binary system. The bacteria were questioned by adding (“one”) or not adding (“zero”) four specific chemicals. The bacterial artificial neural network analysed the data and responded by producing different fluorescent proteins. For example, when we asked if three is a prime number, in response to this question, the bacteria glowed green to print “yes”. Similarly, when we asked if four was a prime number, the bacteria glowed red and said “no”.
How could such a biocomputer be used in real-world applications?
Bacteria are tiny organisms, about one-twentieth the diameter of a human hair. It is not possible to make a silicon computer so small. Making such a small computer with bacteria will open a new horizon in microscale computer technology. Its use will extend from new medical technology and material technology to space technology.
For example, one may imagine a set of engineered bacteria or other cells within the human body taking decisions and acting upon a particular disease state, based on multiple biochemical and physiological cues.
Scientists have proposed using synthetically engineered organisms to help in situ resource utilization to build a human research base on Mars. However, it may not be possible to instruct each of the organisms remotely to perform a specific task based on local conditions. Now, one can imagine the tiny engineered organisms working as a biocomputer, interacting with each other, and taking autonomous decisions on action without any human intervention.
The importance of this work in basic science is also immense. We know that recognizing prime numbers or vowels can only be done by humans or computers – but now genetically engineered bacteria are doing the same. Such observations raise new questions about the meaning of “intelligence” and offer some insight on the biochemical nature and the origin of intelligence.
What are you planning to do next?
We would like to build more complex biocomputers to perform more complex computation tasks with multitasking capability. The ultimate goal is to build artificially intelligent bacteria.
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