Bacterial Clock – improved version
Scientists of the branches of the University of California at San Diego, working under the leadership of Jeff Hasty, have created a living clock mechanism - a biological oscillator, which is a colony of genetically modified bacteria that, thanks to the simplest genetic scheme, emit rhythmic synchronized pulses of fluorescent radiation for 50-100 minutes.
In fact, the development is the first synchronized genetic oscillator, the creation of which is a very important achievement of synthetic biology. In the future, based on such an oscillator, it will be possible to create biosensors for the detection of various toxins and systems for the metered administration of drugs.
Oscillators are the most important mechanism of the biological world, determining numerous cyclical processes, ranging from heartbeat and brain waves to circadian rhythms. They are also important control mechanisms of electronic circuits. More than 10 years ago, biologists developed the first artificial version of the biological oscillator, called the "repressilator". (The year 2000, in which the repressilator and the first genetic switch were created, is considered the year of the birth of synthetic biology.) However, the first oscillators lacked accuracy: the rhythm they measured was quickly disrupted, and the frequency and amplitude of the oscillations could not be controlled.
In 2008, Jeff Hasty and his colleagues created the next, more reliable oscillator, which was tuned by changing the temperature of the bacterial culture medium, the concentration of nutrients contained in the medium and specific chemical agents. However, such oscillators were represented by individual cells, since the bacteria did not want to work synchronously. In their new work, the results of which were published in the journal Nature on January 21 in the article "A synchronized quorum of genetic clocks", the authors improved their development by forcing bacteria to work in unison due to the molecular mechanism used by many microorganisms to communicate with each other.
The new oscillator functions due to a complex of two genes that provide both a positive and negative feedback loop. This complex is activated by a signaling compound that simultaneously triggers its own synthesis and the synthesis of a glowing green fluorescent protein. Signaling molecules coming out of the cell trigger the described mechanism in other bacteria of the colony.
Activation of this mechanism also triggers the synthesis of a protein that destroys the signal compound, thereby ensuring a delayed stop of the cycle. Dynamic interactions of various components of the mechanism inside the cell and between neighboring cells provide regularly repeated emissions of a signal compound and a fluorescent protein, which is externally manifested by flashes and attenuation of the glow. According to Martin Fussenegger, a bioengineer from the Swiss Federal Institute of Technology in Zurich, this is practically the same as ensuring the synchronous operation of traffic lights around the world.
Individual frames give a very rough idea of the work of the bacterial clock,
but the whole video is very impressive, take a look.
The authors grow bacterial colonies in microfluidic chips of their own production, which allow changing the cultivation conditions. For example, a change in the rate of nutrient intake inside the chip changes the oscillation period.
Synchronization of the activity of an entire population of microorganisms can be used in a wide range of technologies, ranging from biomedicine to bioenergy. For example, bacterial oscillators can be used to detect toxic substances: the frequency of fluorescent pulses will be proportional to the concentration of the toxin in the environment. Another promising area of use is the introduction into the body of various drugs, such as insulin, the action of which is most effective when administered at certain intervals. In this case, the power or amplitude of the oscillation will be responsible for the dosage of the drug, and the frequency will be responsible for the intervals between injections.
Currently, researchers are observing the pulsating glow of bacterial colonies in a microscope, but they are already working on creating a version of the oscillator, the glow of which will be visible to the naked eye. They also try to increase the duration of the period of synchronous activity of bacteria. In the future, they plan to combine their approaches with those used in the development of earlier versions of genetic oscillators, and transfer the entire technology to other cell types more suitable for various areas of biotechnology.
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of TechnologyReview: A Synchronous Clock Made of Bacteria.
22.01.2010