12 February 2013

Bacterial Computer

Zero with E. coli
A logical storage device based on bacteria has been createdDmitry Malianov, "Newspaper.

ru"A logical storage device based on E. coli has been created.

In other words, it is the first, albeit very simple computer that uses the memory function and computing power of a living cell.

Engineers from the Massachusetts Institute of Technology (MIT) have designed molecular genetic circuits that allow not only to perform logical operations inside bacteria, but also to remember their results, which are recorded in cellular DNA and transmitted to the next generations of organisms. This technology, described in an article in Nature Biotechnology (Piro Siuti, John Yazbek & Timothy K Lu, Synthetic circuits integrating logic and memory in living cells), can be used to create cellular biosensors with memory function, analog-to-digital biointerfaces, as well as for programming stem cells in order to obtain cells of the desired (differentiated) type.

Figure from the MIT press release: Cell circuits remember their history – VM.

A living cell is a miniature molecular computer created by nature itself, capable of both transmitting information to the next generations of its own kind, and performing logical operations in the process of such transmission, as well as adapting to the environment by processing signals coming into it from the outside. Methods of genetic engineering allow manipulating these processes – creating, for example, new organisms with specified properties or using DNA as memory devices, recording non-biological information in them, moreover, such carriers can be both living cells and arrays of artificially synthesized DNA encoding bits according to a particular algorithm.

The computational potential of DNA is also being actively studied: technologies that allow performing basic logical operations using synthetic DNA "in vitro" are being investigated. The next step should be the creation of a full-fledged DNA computer combining the functions of a molecular processor and DNA memory, and the development of MIT for the first time implements such a computer, moreover, not "in vitro", but inside a living unicellular organism that does not lose the ability to reproduce.

Why do we need such technologies? "The main goal of synthetic biology is to create cellular devices capable of processing input signals, making decisions and triggering," the authors of the article define the strategic task of programming living matter very succinctly.

Actually, in living systems, the strategy aimed at retaining, changing and transmitting information has already been implemented in the course of natural evolution. In artificial cells, programmed cells, in addition to natural activity, process information in parallel according to algorithms set from the outside. For this purpose, genes artificially embedded in DNA and various molecular factors are used that turn these genes on and off according to a known scheme.

By taking a combination of factors as an "input", and gene expression, that is, the production of a certain protein by a cell (for example, fluorescent), as an "output", it is possible to program genetically modified cells as logic gates - basic devices that perform elementary logical operations similar to electronic circuits based on field–effect transistors that are used in digital computing cars.

The MIT team improved this technology and created a cellular valve with a memory function that not only performs a logical operation, but also remembers the input signal that triggered the valve.

Take, for example, the simplest cell valve based on E. coli, which implements the logical operation AND (logical "and") by producing a fluorescent protein in response to a combination of two specific input signals. The cellular valve created at MIT will remember these signals once and for all, and protein production will continue even after the signals (stimuli) that triggered this process disappear. How exactly is the memory function implemented, eliminating the need to constantly stimulate the valve cells, which simply remember their logical position in the next generations of cells?

The function of such a memory "gate" is played by a sequence of nucleotides specially placed between the promoter (a section of DNA recognized by RNA polymerase as a reference point for reading information and subsequent transcription of the gene) and the actual sequence encoding the protein. This embedded sequence, called a "terminator", suppresses the transcription of the fluorescence gene, but it, in turn, can be deactivated by a certain recombinase enzyme – a protein that cuts, reverses and recombines sections of DNA. When a certain recombinase enzyme is activated, which occurs only when two different input signals are simultaneously applied, the nucleotide sequence of the terminator site is turned off (rotated 180 degrees), the gene is transcribed, and the bacterium glows, but the terminator can no longer return to its initial position, preventing gene expression in either this or the next generation of E. coli.

In total, the authors of the article studied 90 generations of gate bacteria, and they all remembered the event that triggered the logical operation "and", as well as a number of other logical operations, although the initial signals had already disappeared.

Thus, the history of bacteria (or the condition of the valves, as well as the disappeared signal that caused this condition) can be traced simply by measuring the level of their glow. And even if the bacteria die, the value and history of the valves can be restored by deciphering microbial genomes.

Using this technology, the MIT team implemented 16 logic gates (OR, FALSE, XOR, etc.) with a memory function using modified types of E. coli. Such valves can be used as biosensors tuned to certain molecules, and the output signal of which can be used to judge the presence of certain compounds in the environment.

For example, if such a sensor has two different input signal circuits that affect the level of expression of the fluorescent gene, then at the output we get four signal variations, by which we can judge what kind of effect the sensor was exposed to. Using this approach, it is possible to program bacteria in advance, which in all subsequent generations will respond to certain signals in a strictly defined way, which will allow for more subtle regulation of the production process of medicines or, for example, biofuels. Finally, it is also possible to carefully control the process of differentiation of stem cells into cells of a certain type by means of the computational potential of cells, which, once having memorized the input signal, will repeat in subsequent generations the desired "output", that is, the type of cell.

It is possible that in the future it will also be possible to create artificial ensembles of cells using the maximum possible number of logical operations for processing signals of different types, as well as for memorizing and making decisions.

Portal "Eternal youth" http://vechnayamolodost.ru12.02.2013

Found a typo? Select it and press ctrl + enter Print version