More complex circuits for synthetic biology lead toward engineered cells

The protein–protein and protein–DNA interactions that can lead to crosstalk between gates are shown as red rectangles. (Credit: Tae Seok Moon et al./Nature)

One possible pathway from current technology to advanced nanotechnology that will comprise atomically precise manufacturing implemented by atomically precise machinery is through adaptation and extension of the complex molecular machine systems evolved by biology. Synthetic biology, which engineers new biological systems and function not evolved in nature, is an intermediate stage along this path. An article on KurzweilAI-net describes a recent achievement by MIT scientists in constructing a synthetic genetic circuit that responds to control signals from four molecules without any one molecule interfering with the responses to any other molecules. From “The most complex synthetic biology circuit yet“:

Christopher Voigt, an associate professor of biological engineering at MIT,.and his students have developed circuit components that don’t interfere with one another, allowing them to produce the most complex synthetic circuit ever built.

The circuit integrates four sensors for different molecules. Such circuits could be used in cells to precisely monitor their environments and respond appropriately.

Using genes as interchangeable parts, synthetic biologists design cellular circuits that can perform new functions, such as sensing environmental conditions. However, the complexity that can be achieved in such circuits has been limited by a critical bottleneck: the difficulty in assembling genetic components that don’t interfere with each other.

Unlike electronic circuits on a silicon chip, biological circuits inside a cell cannot be physically isolated from one another. “The cell is sort of a burrito. It has everything mixed together,” says Voigt.

Because all the cellular machinery for reading genes and synthesizing proteins is jumbled together, researchers have to be careful that proteins that control one part of their synthetic circuit don’t hinder other parts of the circuit. …

The pathway consists of three components: an activator, a promoter and a chaperone. A promoter is a region of DNA where proteins bind to initiate transcription of a gene. An activator is one such protein. Some activators also require a chaperone protein before they can bind to DNA to initiate transcription. …

To design synthetic circuits so they can be layered together, their inputs and outputs must mesh. With an electrical circuit, the inputs and outputs are always electricity. With these biological circuits, the inputs and outputs are proteins that control the next circuit (either activators or chaperones). …

The research was published in Nature [abstract]. The authors conclude “This work demonstrates the successful layering of orthogonal logic gates, a design strategy that could enable the construction of large, integrated circuits in single cells.” Certainly there are many steps between engineering cells to optimize their normal outputs to achieve engineered purposes, and engineering cells for entirely novel nanofabrication of materials not normally found in biology, but the more complex the tools that are available, the more opportunities there will be to advance along this path. Whether or not we can go all the way along this path from engineering biology to molecular manufacturing remains to be seen.
—James Lewis, PhD

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