06 October 2008

A new achievement in bacterial training

A hundred years after Pavlov's dog first started salivating at the sound of a bell, scientists claim that in a similar way it is possible to "train out" single-celled organisms, for example, bacteria. The difference lies in the fact that bacteria will use molecular mechanisms instead of complex complexes of neurons to "memorize" associations of two stimuli.

In 1945, the Canadian neurophysiologist Donald Hebb explained the phenomenon of conditioned reflex and other variants of associative learning by the fact that a physical relationship is formed between neurons simultaneously generating signals, which is amplified by repeated simultaneous activation of cells. As a result, when exposed to one of the signals, neurons of both types begin to generate nerve impulses, and the associations between the two stimuli become stronger the more often they act simultaneously.

Bacteria and other unicellular organisms do not have nerve cells and synapses, but there is a possibility that they are also capable of learning. In the 70s, Todd Hennessey experimented with unicellular pond inhabitants – infusoria-shoes. He subjected them to an electric current, accompanied by the sound of a bell. As a result, the infusoria began to float away from the sound source even in the absence of electric shock. Other researchers have not been able to reproduce these results, and the intriguing possibility of training single-celled organisms remains unconfirmed.

In an article published in the October issue of the Journal of the Royal Society Interface, an international group of researchers from Germany, Holland and the United Kingdom proposes a method of "training" bacteria – but not by developing conditioned reflexes in them, but using genetic engineering. According to the head of the study, Crisantha Fernando, this approach makes it possible to turn bacteria into a kind of "sentinels" of the body, constantly in a state of readiness to recognize danger signs and respond to them.

The authors have developed a cellular circuit consisting of several genes and their promoters and producing proteins (transcription factors) that activate and inactivate each other like relays in an electrical circuit. The theoretical circuit proposed by them consists of three functional genes. Two of them – A and B – synthesize proteins pA and pB, reacting with other transcription factors – iA and iB – in order to activate the third gene – C.

The products of the activity of the pA and pB genes will be stored in the cell for a long time and act as a kind of memory. Their concentrations are equivalent to the number of synapses in the Pavlov dog model. Only when interacting with these molecules, iA and iB can have their inherent effects. If researchers pair iA and iB, the bacteria begin to react to iB, whereas previously they only reacted to iA. This means that the bacteria have "learned" to react to iB.

Experts in this field consider the proposed approach conceptually complex at first glance, but quite viable on closer examination.

The model is based on the assumption that a chemical-genetic chain can be created and implanted into a bacterium, for example, into an E. coli. According to the authors, changes induced in bacteria can persist during the 30-minute life cycle of E.coli. This will make the changes heritable, which is especially important for the use of "trained" bacteria in medicine.

The authors plan to "train" bacteria to recognize chemical processes associated with danger in the body. Such a "live indicator" can be configured in such a way that the synthesis of a signaling protein begins in response to the appearance of molecules in the body that are characteristic of the undesirable effects of drugs or indicate the presence of malignant tumors.

Work with genetically modified, externally controlled bacteria has been going on for years. The possibility of creating biosensors from "trained" bacteria using genetic engineering should give rise to a new direction of work in this field of research.

Portal "Eternal Youth" http://vechnayamolodost.ru / based on the materials of Technology Rewiev – Teaching Bacteria to Behave 

06.10.2008

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