A genetic system developed by researchers at the Hebrew University of Jerusalem allows cells to process several signals simultaneously, choose a response based on the combination of signals, and even alert to an abnormal condition. In the future, the approach may be used to develop therapeutic cells that will recognize signs of disease and activate targeted treatment.
Researchers fromThe Hebrew University Developed an artificial genetic system that allowshuman cells Perform complex logical operations and make decisions based on several biological signals simultaneously. The system does not turn the cell into an electronic computer, but it mimics within the cell some of the basic operations performed by digital circuits.
The study, published in the journal Nature Communications., was conducted by doctoral student Keren Roas and Dr. Lior Nissim. The researchers built artificial genetic systems inside human cells that are capable of absorbing information, processing it, and activating genes according to a predetermined program.
According to the researchers, one of the main advantages of the method is the ability to perform complex calculations using a relatively small number of steps and genetic components. Reducing the number of steps is important because in biological systems, each additional step can reduce the accuracy and reliability of the response.
A cell that receives several signals and decides how to respond
One goal of synthetic biology is to create cells that can be programmed to perform specific tasks. For example, imagine a cell that recognizes several signals indicating the presence of a cancerous tumor, but only triggers a therapeutic response when all the appropriate conditions are met.
In previous systems, each additional logical operation sometimes required the construction of an additional genetic layer. As the number of layers increases, the signal can weaken, the response time increases, and the system becomes more sensitive to errors.
"Our new approach allows cells to execute complex programs using a much smaller number of calculations and genetic components," said Dr. Nissim. According to him, the method may enable the construction of more advanced biological systems without compromising their function.
The researchers relied on a process called splicing RNA In the crossover – RNA trans-splicing. In this process, separate parts of RNA molecules can be joined together inside the cell and used to create an active genetic message.
They combined the splicing mechanism with natural and artificial control elements that they designed. The elements act as a kind of biological processors: they receive signals, examine whether a certain combination of conditions is met, and then activate a pre-selected gene.
Full connector and multiplexer inside a compartment
To demonstrate the system's capabilities, the researchers built biological devices that are equivalent to familiar components from the world of digital electronics.
One of them was Full connector – full adder. This is a basic logic circuit that adds binary digits and also takes into account the carry obtained from a previous addition operation. Such circuits are used as building blocks in the calculation units of processors.
In the biological version, the signals are not electrical currents but molecules and processes within the cell. The result is not displayed as a number on a screen, but is expressed in the activation of genes and the production of proteins.
The researchers also built a biological version of Multiplexer – multiplexer. In an electronic component, a multiplexer selects one signal from several possible signals and passes it on according to a control signal. In a biological system, a cell chooses between several genetic responses depending on the input it receives.
To monitor the systems' activity, the researchers used fluorescent proteins that glow in different colors. Each color provided a signal that a particular genetic pathway was activated.
Fault condition warning mechanism
The system also included a mechanism designed to detect abnormal input combinations or overload conditions. When the cell detected such a condition, it would generate a special warning signal.
In a future therapeutic system, a similar mechanism could serve as a kind of safety layer. Instead of continuing to trigger an inappropriate response, the cell could stop the action, activate a defense mechanism, or signal that there is a malfunction.
Safety mechanisms are especially important when designing cells for medical use. A wrong response could cause a therapeutic cell to act in healthy tissue or produce an unwanted amount of an active substance.
Towards smart therapeutic cells
One of the long-term goals of the research is to develop Therapeutic cells That they can monitor their environment and only act when they identify a precise combination of disease markers.
Such a cell could, for example, simultaneously check for the presence of several proteins or chemical signals. Only if they all match the pattern characteristic of a cancer cell will it activate a therapeutic agent. This would make it possible, at least in principle, to minimize damage to healthy cells.
As a demonstration of a therapeutic possibility, the researchers programmed cells to produce Interleukin 15, or IL-15. It is an immune system signaling protein that is capable of stimulating the activity of cells involved in the anti-tumor response.
IL-15 production could illustrate how a programmed cell might release an active substance only after it has detected a specific combination of signals. However, this is still an experimental system, not a treatment that could be used in humans.
Before programmed cells can be implemented in the body, it will be necessary to test the stability of the systems over time, the error rate, their effect on the cell, and the risk of unwanted activation.
The research joins a broader effort to transform living cells into programmable systems. Unlike an electronic processor, a cell changes, divides, and responds to a complex environment. Precisely for this reason, it may in the future serve as a therapeutic system capable of sensing the body's condition and responding at the appropriate place and time.
Questions and Answers
What did the researchers develop? An artificial genetic system that allows human cells to process several biological signals and choose a response according to a predetermined program.
Have cells really become computers? No. They are not electronic computers, but the genetic systems within them perform logical operations similar to those of digital circuits.
what is RNA splicing In a crossover? A process in which separate parts of RNA molecules join together within the cell to form an active genetic message.
What computational components were built? A full adder, which performs a binary addition operation, and a multiplexer, which selects one signal from several options.
How did the researchers know which response was triggered? They used fluorescent proteins that glow in different colors and signal the activation of genetic pathways.
What is the safety mechanism in the system? When the cell detects an abnormal signal combination or overload, it generates a warning signal.
What is the possible medical application? Therapeutic cells that can identify a combination of disease markers and release therapeutic material only in the appropriate tissue.
Is the method ready for human treatment? No. This is basic and experimental research, and many tests of efficacy, stability, and safety are required.
More on the subject on the science website
- AI designs “genetic circuits” on a massive scale — and faster than possible manually
- What is the relationship between bacteria and neural networks?
- Researchers have developed a synthetic cell that produces anti-cancer drugs inside the tumor
- Development of an integrated circuit from bacteria
- Rewiring genetic switches
