Synthetic biology allows the building of artificial computational devices inspired in the standard design of electronic circuits by using cellular consortia, including reusable and reprogrammable complex circuits, as shown by Ricard Solé and colleagues. Logic gates for complex Boolean computations can be implemented by engineered yeast cells, which can be combined in multiple ways. Each construct defines a logic function and combining cells and their connections allow building more complex synthetic devices, such a multiplexer or a 1-bit adder with carry. Cellular consortia are an efficient way of engineering complex tasks not easily solvable using single-cell implementations.” Sergi Regot, Javier Macia, et al. “Distributed biological computation with multicellular engineered networks,” Nature, Published online 08 December 2010 [Supplementary Information on Methods; Supplementary Figures].
“Cellular consortia computation is based on the idea that external communication between cells in populations involving either single or multiple cell types would perform functions difficult to be implemented using individual strains. A small library of engineered cell types with restricted connections among them was generated, each cell responding to one/two inputs. The basic two-input and one-output engineered functions include the AND and the inverted IMPLIES (N-IMPLIES), which allow implementing any Boolean function. Moreover, some cells define one-input, one-output function. These cells only respond to an external input and to a single diffusible molecule acting as a wire. Cells can receive signals from other cells (IN) and external sources (E) or just from external sources. Cells can also produce diffusive output molecules.
Most of all possible functions with two and three inputs can be constructed using C = 2–5 different cells. For instance, in response to three inputs, just three cells results in more than 100 functions and exceed 200 using four cell types. With three inputs, over 100 different logical functions can be achieved with only two wires and almost all are obtained with just three to four wires. Reusing cells from AND and NOR circuits three-cell circuits for OR, NAND, XNOR and XOR logic gates were obtained. The approach is adaptable and multiple functions can be constructed from a small library of reusable cells. Once the circuits are turned on, they can maintain maximal signal for periods beyond 9 h in the presence of stimuli. Moreover, the system can be selectively switched off and partially reprogrammed.
A multiplexer MUX2to1 and a 1-bit adder with carry was built in vivo checking the robustness and good performance of the approach. A multiplexer MUX2to1 is a circuit that selects one of different input signals and forwards the selected input into a single output. It can be assembled from just three engineered cell types responding to three input signals and a single wiring molecule, and also using four cell types with two independent wiring molecules. A 1-bit adder with carry is the basic circuit required to build a n-bit adder. It was built by combining XOR and AND gates that respond to the same input with two wiring molecules.
Possible applications in bioengineering and biomedicine will need to address in future work the scalability, strategies for reducing potential crosstalk and the robustness to noise of the new approach. However, the results reported in the paper are very promising.”