29 March 2013

Biotransistor for biocomputers

A DNA-protein analog of a transistor has been created

Kirill Stasevich, CompulentaThe idea of creating a "biological computer" in which logical operations would be performed in a cell using biological macromolecules has been occupying scientists for a long time.

And recently, significant progress has been achieved here. However, existing DNA-RNA-protein "microcircuits" can perform only one specific task – for example, to include a specific gene in response to a specific signal, while they are not able to give a signal of different strength.

Researchers from Stanford University Medical School (USA) have tried to improve existing "molecular calculators". They tried to make a transistor analog out of biomolecules. A classical transistor has two entry points (emitter and collector), between which the main flow of electrons goes, and there is an additional input (base), to which an additional current is supplied and through which the strength of the main one can be adjusted. The current supplied to the control input can be very small, but at the same time significantly change the main current.


The range of the signal available to the DNA transistor, depending on the input data (red – maximum, blue – minimum).
On the left is the theoretically expected gradation, on the right is what happened in practice. (Fig. of the authors of the work.)

In Drew Andy's lab, they undertook to make something similar, but from DNA and proteins. The components were: DNA, the enzyme RNA polymerase, which synthesizes RNA on a DNA template, and integrase enzymes, which can insert pieces of DNA into each other. DNA became the "body" of the transistor, and RNA polymerase molecules became the running electrons. The enzyme sat on the DNA and began to move, synthesizing RNA; thus, the ends of the DNA were like an emitter and collector. But integrase worked as a base: this enzyme determined how many RNA polymerase molecules would go through DNA.

In order for integrase to control the molecular "current", a special nucleotide sequence-terminator- was inserted into the middle of DNA, which inhibited RNA polymerases and forced them to descend from DNA. Integrase could invert this fragment, that is, cut and paste it back, only backwards. As a result, the terminator sequence disappeared (since the current of RNA polymerases went through DNA only in one direction), and a full-fledged mRNA was obtained.

A gene for a green fluorescent protein was recorded in the DNA, so that when the integrase reversed the terminator sequence, the cell began to glow green. This "transcriptor", as the authors of the work call it (a transistor based on transcription), can be adapted to perform logical operations: the integrase controlling the current executes Boolean operators (AND and OR), on which the work of machine logic is based.

It is easy to notice that this study, the results of which are published in the journal Science (Bonnet et al., Amplifying Genetic Logic Gates), is very similar to the work carried out at the Massachusetts Institute of Technology (USA). The difference is that MIT used a similar scheme with a modification of the sequence in DNA to record the result of a specific logical operation in memory, and Stanford scientists solved a slightly different task: they wanted to make a system that can perform different operations and at the same time allow you to adjust the strength of the signal. Researchers have shown how to achieve this: for example, a cell can contain a whole complex of transistor transcriptors with different fluorescent signals, which will receive signals from different sources. On the other hand, there may be many copies of the same transistor at the disposal of the control integrases, and the signal intensity (the intensity of protein production) will depend on how many copies the enzyme allows (or prohibits) its synthesis.

Prepared based on the materials of the Stanford University Medical School:
Biological transistor enables computing within living cells, study says.

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