MIT Engineers Turn Bacteria Into Living Transistors

In conventional electronics, transistors act as switches that control the flow of electrical current. In this MIT-developed biological circuit system, engineered bacterial cells perform a similar function by regulating the movement of small signaling molecules. These chemical signals transmit information between components in synthetic biology circuits.

The researchers developed two types of bacterial transistors along with three additional bacterial strains that function as relays. Together, the five strains create a modular toolkit that can be arranged to build a wide range of biological circuits. In the new study, the team demonstrated circuits capable of adding two or three inputs and routing a single input to a selected destination.

“We built some of the earliest commonly used computer architecture components, and you can use these five strains to build any operation,” said Hamid Doosthosseini PhD ’25, an MIT postdoctoral researcher and lead author of the study.

One potential application is embedding these living circuits in plant leaves or roots. The engineered bacteria could process information about environmental conditions and help plants detect and respond to stresses such as drought, disease, or pest attacks.

Christopher Vogt, chair of the Massachusetts Institute of Technology’s Department of Bioengineering, is the senior author of the paper, which was recently published in Nature Chemical Biology. Former MIT postdoctoral researcher Haorong Chen is also an author.

Engineering bacterial cells to work like transistors

Synthetic biology circuits are typically built by engineering cells to produce interacting proteins and transcription factors. These biological systems can be programmed to detect specific molecules and generate targeted responses.

Although synthetic biology circuits can perform many logical functions, their complexity is often limited. Researchers generally need separate transcription factors for different operations to prevent signals from interfering with one another. Because only a limited number of suitable transcription factors are available, there is a practical limit to how complex a circuit can become inside a single cell. Packing too many circuits into one cell can also overload its protein-production machinery.

The MIT team took a different approach. Instead of placing an entire circuit inside one cell, the researchers engineered individual cells to act as transistor-like components that could be connected in multiple configurations.

For their biological components, the researchers used Pantoea agglomerans, a bacterium commonly found on plant surfaces. They engineered two versions of a bacterial transistor that respond to a molecule called OC6. One version switches on when it detects the molecule, while the other switches off.

Each transistor also detects a second target molecule, OC12. Depending on whether OC12 is present and whether the transistor is active, the bacterial cell produces an output molecule called OHC14.

Connecting living cells into biological circuits

The team engineered three strains of Pantoea agglomerans to serve as repeaters. These cells convert the OHC14 signal into another output that can act as an input for the next transistor. This process allows individual bacterial components to be “wired” together in much the same way as components on an electronic circuit board.

For example, the researchers built a bidirectional switch using two transistors that detect OC12. Depending on a separate control input, the system sends the signal through another relay chain, which passes the information to additional transistors for further processing.

To assemble the circuits, the researchers printed bacterial colonies onto agar plates, which provided a suitable growth medium. Each colony was positioned approximately 5 millimeters from its nearest neighbor. This spacing helped ensure that chemical signals reached only the next colony in the array, allowing information to travel in a controlled direction.

Creating more complex biological computing systems

The researchers demonstrated that the same bacterial transistor can perform different logical operations depending on its position within a circuit. These operations include multi-input gates, OR gates, and implication gates.

By connecting several transistors, the team created a more advanced biological computing system. The circuit can add two signals, process multiple signals at the same time, and function as a demultiplexer. A demultiplexer receives one input signal and routes it to one of several possible destinations based on a separate control signal.

The largest circuit demonstrated in the study contained 24 interconnected bacterial colonies and was designed to add two inputs.

“This study shows that by linking together the simple functions of individual cells, we can arrive at more complex functions,” Vogt says. “Mathematically, there’s nothing you can do on an iPhone that you can’t do with these circuits.”

However, biological circuits operate much more slowly than electronic computers. Each calculation performed by the bacterial system takes approximately eight hours. For biological applications, the researchers say this timescale could still be practical.

“We’re not trying to replace computers, but rather introduce computational control into biology. If you have bacteria in the roots of plants, or if the plants themselves are doing the calculations, performing simple calculations overnight is fast enough compared to the growing season,” Vogt says.

Agricultural applications for living computers

One potential use for these living bacterial circuits is agriculture. If the systems can eventually be placed in plant roots, they could be programmed to detect different types of environmental stress. When the circuit recognizes a specific signal, it could trigger a corresponding response, such as producing a protective compound or activating a defense mechanism.

This research was funded in part by the U.S. Defense Advanced Research Projects Agency and the U.S. Intelligence Advanced Research Projects Activity.