Analog-to-digital converters based on DNA
Gene "circuits" allow living cells to perform complex analog and digital calculations
DailyTechInfo based on KurzweilAI materials: Gene circuits in live cells that perform complex analog/digital computations
Researchers from the Massachusetts Institute of Technology have developed a kind of synthetic gene "circuits" in which a combination of analog (continuous) and digital (discrete) computing technologies is implemented. The introduction of such schemes into the genetic code of living cells will allow these cells to perform complex data processing operations and, based on them, perform various programmed actions, for example, to release the appropriate drug when the glucose level drops below a certain set value.
Like electronic circuits, living cells are able to independently perform some calculations in continuous (analog) or discrete (digital) modes. An example of analog "calculations" is the function of the adaptation of eye cells to changes in the level of illumination, and digital – the death (apoptosis) of the cell in response to changes in certain environmental conditions. Scientists have been experimenting with creating artificial computational "circuits" embedded in living cells for a long time, but in most cases scientists manage to implement either only digital or only analog computing methods.
The basis of digital systems is a simple binary code consisting of a sequence of 0 and 1. With this approach, complex computational operations require circuits consisting of a large number of elements performing various basic logical functions – AND, OR, XOR, NOT, NAND, NOR and XNOR. And such schemes are quite difficult to create at the biological level.
Using sections of synthetic DNA, biologists can create circuits that perform functions beyond the above set of basic logical functions. "Most of the work in the field of synthetic biology has been focused on digital computing due to the fact that this approach makes it quite easy to program cells," says Timothy Lu, professor at the Massachusetts Institute of Technology, "The genetic circuits we have developed allow us to measure the levels of "analog" signals, for example, concentration a certain substance. And on the basis of these data, the circuit can perform an action, the result of which can be issued again in analog form, for example, in the form of the amount of the drug being produced, or in digital form – the death of a cell affected by the disease."
New genetic schemes have a rather complex structure. The first mandatory part of them is a "sensor" that measures the concentration of a certain substance or other environmental parameters. The signal from this sensor affects the recombinase gene, which activates or deactivates certain DNA regions, which, in turn, produce either a digital or analog output signal. The closest analogue from the world of electronics of such a chain is a digital comparator.
On the basis of such primitive comparator elements, scientists have created a more complex device, an analog-to-digital converter (ADC), which converts an analog signal into a digital one based on ternary logic. In the future, such devices will be able to detect changes in the concentration of substances in the blood and develop three or more options for action. For example, if the blood glucose level is too high, then cells can produce and release insulin, if the glucose concentration is too low, then cells need to produce glucagon. And if the glucose concentration is normal, then nothing needs to be done.
In the figure from the article Rubens et al. Synthetic mixed-signal computation in living cells (Nature Communications, 2016) is a simpler example: synthesis of a given protein at different concentrations of two signaling substances.
On the left is the percentage of cells expressing green fluorescent protein (GFP) depending on the concentration of hydrogen peroxide in the presence (black squares) and absence (red circles) in the culture medium of anhydrotetracycline (aTc).
On the right is a diagram of the operation of the gene analog-to–digital converter - VM, which provides this mechanism.
Such gene schemes can be embedded not only in cells of normal tissues, turning them into factories for the production of medicines. Exactly the same approach can be used to program cells of the immune system. Having received circuits with sensors of various types, immune cells can analyze oxygen levels and other symptoms of cancer. And, depending on these levels, they will be able to choose one or another method of influencing diseased cells, up to their complete destruction.
Now researchers from the Massachusetts Institute of Technology have organized a company called Synlogic, whose specialists are engaged in designing simple gene circuits that will be embedded in the genetic code of bacteria species useful for the human body. After such an introduction, these bacteria will be able to independently fight diseases and harmful bacteria living in the human intestine. And the first clinical trials of a bacteria-based treatment method will begin within the next year.
Portal "Eternal youth" http://vechnayamolodost.ru 23.06.2016