MIT researchers have engineered bacteria that can function as transistors, allowing the team to create living "circuit boards" that can be printed onto a growth medium in a Petri dish.
In electrical circuits, transistors function as switches that can turn current on or off. In the biological circuits that the researchers have created, bacterial switches control the flow of small molecules, which send signals to downstream circuit components.
The research team designed two different transistors, along with three bacterial strains that relay information between the transistors, giving them the building blocks they need to design nearly any type of circuit. In a new study, they used these cells to create circuits that can add two or three inputs, or send one input to a specific location in the circuit.
"We've built some initial computer architecture components that are commonly used, but any operation can be built with these five strains," says Hamid Doosthosseini PhD '25, an MIT postdoc and the lead author of the new study.
Using this approach, the researchers hope to develop circuits that one day could coat plant leaves or roots, where they could compute to sense and respond to environmental conditions such as drought or attack by pests.
Christopher Voigt, head of MIT's Department of Biological Engineering, is the senior author of the paper, which was recently published in Nature Chemical Biology . Former MIT postdoc Haorong Chen is also an author of the paper.
Cells as transistors
When designing synthetic biology circuits, researchers typically engineer cells to express proteins and transcription factors that interact to perform a task such as sensing a target molecule, which then triggers production of a specific output.
These simple circuits can perform various logic functions, but they must use unique transcription factors to avoid crosstalk within the circuit. There is a limited number of transcription factors that can be used for these circuits, which limits the overall complexity that can be achieved in a single cell. Additionally, putting too many circuits in one cell can overburden the cell's protein production machinery.
In the new paper, the researchers took a different approach: Instead of building an entire circuit into one cell, they designed cells that could act as transistors. These transistors can then be combined in different ways to create a variety of circuits.
To create the transistors, the researchers chose a bacterium called Pantoea agglomerans, which commonly grows on surfaces, including plants. Using these cells, they made two types of transistors that can be switched on or off by a molecule called OC-6. One of the transistors is switched on by this input, and the other is switched off. Each transistor also detects the presence of a target molecule, in this case, OC-12. Depending on whether that molecule is present, and whether the switch is active, the transistors produce an output molecule known as OHC-14.
The researchers also used three strains of Pantoea agglomerans to create relays, which translate the OHC-14 signal into an output that can be fed into another transistor. Using these relay strains, the researchers can "wire" the transistors together, just like an electronic circuit board.
For example, they could create a bidirectional switch with two transistors that sense OC-12, and then send that information to different relay strains based on a switch input, ultimately feeding into other transistors that further process the signal.
The researchers created their circuits by printing colonies of bacteria onto plates containing agar, a growth medium. Each colony is printed about 5 millimeters from the nearest one. This allows the signals to travel only to the nearest colony, which then relays them to the next one, so information flows only in one direction.
Credit: Courtesy of the researchers
Complex calculations
In this paper, the researchers demonstrated a transistor that can perform several types of logic operations depending on its location in the circuit layout, including "multi-input," "or," and "imply" gates. They also combined the transistors to create more complex circuits that can add up two signals, process more signals simultaneously, or function as a demultiplexer - a circuit that takes one incoming signal and sends it to one of several possible destinations, depending on a control signal.
The largest of these circuits, which adds two inputs together, contains 24 bacterial colonies wired together.
"This work shows that we can get toward more complicated functions by linking up simpler functions in individual cells," Voigt says. "Computationally, there's nothing that your iPhone can do that these circuits couldn't do."
Circuits made from these cells take about eight hours to perform each calculation, much longer than a computer circuit. But, for biological applications, that is a reasonable amount of time, the researchers say.
"We're not trying to replace computers, but rather put computational control into biology. If you have bacteria on the root of a plant, or the plant itself is doing the computing, running a simple calculation overnight is fast enough relative to a growth season," Voigt says.
If developed for use in agriculture, this type of circuit could be applied to the roots of plants to detect different types of stress. Once a particular input is detected, it would trigger a response such as synthesizing a fungicide.
The research was funded, in part, by the U.S. Defense Advanced Research Projects Agency and by the U.S. Intelligence Advanced Research Projects Activity.
