Biosynthetic dual-core computer in a living cell

ETH scientists have integrated two processor cores based on CRISPR-Cas9 into human cells. This is a huge step towards creating powerful bio-computers.

Managing gene expression using gene switches based on a model borrowed from the digital world has long been one of the main problems of synthetic biology. The digital method uses logic elements to process input signals, creating circuits in which, for example, the output signal C is created only when the input signals A and B are simultaneously present.

Until now, bioengineers have tried to create such digital circuits using protein gene switches in cells. However, they had serious shortcomings: they were not flexible, they could only understand simple programs and were able to process only one input at a time, for example, a specific molecule. Thus, more complex computational processes in the cell were possible only under specific conditions, unreliable and often failed.
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Even in the digital world, circuits depend on one input in the form of electrons. However, such schemes compensate for this with their speed, executing billions of commands per second. Cells are slower compared to them, but can process 100,000 different molecules per second as input. And yet, past cellular computers did not even come close to exhausting the enormous computational capabilities of a human cell.

Cpu of biological components

A team of researchers led by Martin Fussenegger, a professor of biotechnology and bioengineering in the Department of Biological Sciences and Engineering at ETH Zurich in Basel, has now found a way to use biological components to create a flexible CPU that accepts various programs. The processor, developed by ETH scientists, is based on the modified CRISPR-Cas9 system and can work with any number of inputs in the form of RNA molecules.

A special variant of Cas9 protein forms the core of the processor. In response to the input carried out by the RNA guides, the processor regulates the expression of the gene, which, in turn, produces a certain protein. Through this approach, researchers can program scalable circuits in human cells — for example, digital adders, they consist of two inputs and two outputs, and can add two single-digit binary numbers.

Powerful multi-threaded information processing

The researchers took another step: they created a biological dual-core processor, similar to the digital one, by integrating the two cores into a cell. To do this, they used the components of CRISPR-Cas9 from two different bacteria. Fussenegger was delighted with the result, saying: "We created the first cellular computer with several cores."

This biological computer is not only extremely small, but theoretically it can be increased to any possible size. “Imagine a fabric with billions of cells, each equipped with its own dual-core processor. Such “computational authorities” can theoretically reach computing power that far exceeds the computing power of a digital supercomputer — and uses only a small part of the energy, ”says Fussenegger.

Application in the diagnosis and treatment

A cellular computer can be used to detect biological signals in the body, such as metabolic products or chemical signals, to process them and respond accordingly. With a properly programmed processor, cells can interpret two different biomarkers as input signals. If only biomarker A is present, then the biocomputer responds by forming a diagnostic molecule or pharmaceutical substance. If the biocomputer registers only the biomarker B, it starts the synthesis of another substance. If both biomarkers are present, this triggers a third reaction. Such a system can be used in medicine, for example, in the treatment of cancer.

“We could also integrate feedback,” says Fussenegger. For example, if the biomarker B remains in the body for a longer period of time at a certain concentration, this may indicate cancer metastasis. The bio-computer will produce a chemical aimed at eradicating cancer.

Multi-core processors are possible.

“This cellular computer may seem like a very revolutionary idea, but it’s not so,” emphasizes Fussenegger. He continues: “The human body itself is a big computer. His metabolism uses the computational power of trillions of cells from time immemorial. " These cells constantly receive information from the outside world or from other cells, process the signals and react accordingly - be it chemical signals or the start of metabolic processes. “And unlike the electronic supercomputer, this big computer needs only a piece of bread,” notes Fussenegger.

His new goal is to integrate a multi-core computer structure into a cell. "It will have more computing power than the current dual-core structure."