Dual-processor cellular computers
CRISPR was used to create cellular computers
Lina Medvedeva, XX2 century
Researchers from the Swiss Higher Technical School of Zurich (Eidgenössische Technische Hochschule Zürich) integrated two processors based on CRISPR-Cas9 technology into human cells. This is a huge step towards the creation of powerful biocomputers.
The control of gene expression by switching, based on a model from digital reality, has long been one of the main tasks of synthetic biology. In digital technologies, so-called logic gates are used to process incoming signals, that is, circuits are created where the output signal C is produced only when the input signals A and B are simultaneously present.
Today, with the help of biotechnologies, they are trying to build similar digital circuits using protein switches of genes in cells. However, they have some serious drawbacks: they are inflexible, can only make a simple software decision and process only one incoming signal at a time, for example, a specific molecule in metabolism. More complex computational processes in cells are possible only under certain conditions, they are unreliable and often fail.
Even in the digital world, the operation of the chain depends on a single input in the form of electrons. However, digital circuits compensate for this with speed, executing up to a billion commands per second. Cells are slower in comparison, but they can process up to 100,000 different metabolic molecules per second as input. And yet the previous cellular computers did not even come close to using the huge metabolic capabilities of the human cell.
A group of researchers led by Martin Fussenegger has found a way to use biological components to create a flexible processor core, or central processing unit (CPU), which can be programmed in various ways. This processor is based on a modified CRISPR-Cas9 system. It can work with any amount of input data in the form of RNA molecules (known as RNA conductors).
Article by Kim et al. A CRISPR/Cas9-based central processing unit to program complex logic computing in human cells is published in the journal PNAS.
The processor core is formed by a special kind of Cas9 protein. In response to the input signal coming from the sequences of RNA conductors, the central processor regulates the expression of a specific gene, from which, in turn, a certain protein is obtained. With this approach, researchers can program circuits of different scales in human cells. For example, digital half-sums consisting of two inputs and two outputs, adding two single-digit binary numbers.
The researchers went even further – they created a biological dual-core processor similar to an electronic one by integrating two cores into the cell. To do this, they used CRISPR-Cas9 components from two different bacteria. Fussenegger says: "We have created the first cellular computer with multiple processors."
This biological computer is extremely small, but, theoretically, it can be scaled to any conceivable size.
"Imagine a micro-tissue with billions of cells, each of which is equipped with a dual-core processor. Such a "computing body" can achieve computing power far exceeding that of a digital supercomputer using only a little energy," says Fussenegger.
With the help of a cellular computer, it will be possible to detect biological signals in the body, for example, certain metabolic products or informational RNAs. It could process the signals and react accordingly. With a properly programmed processor, cells can interpret two different biomarkers as an input signal. If only biomarker A is present, the biocomputer will form a diagnostic molecule or pharmaceutical substance. If only biomarker B is registered, it will start the production of another substance. If both biomarkers are present, this will trigger a third reaction. Such a system can find application in medicine, for example, in the treatment of cancer.
"We will be able to integrate feedback into this system," says Fussenegger. For example, if biomarker B remains in the body for a long period of time at a certain concentration, this may indicate cancer metastases. The biocomputer will then produce a chemical intended for treatment.
"A cellular computer may seem like a revolutionary idea, but it's not," Fussenegger emphasizes. – The human body itself is a big computer. Since time immemorial, metabolism has relied on the computing power of trillions of cells." These cells constantly receive information from the outside world or from other cells, process signals and react accordingly – they produce informational RNAs or start the metabolic process.
"Unlike a technical supercomputer, this huge computer only needs a small piece of bread to generate energy," Fussenegger notes.
The next goal is to integrate a multicore computer structure into a cell. "This would give even more computing power than the current dual–core structure," he concludes.
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