Team:XMU-China/Project

It’s an inspiring story about how some oscillation bacteria synchronized via two levels of communication method and formed their own glee: synchronized oscillation. Finally, they got a chance to perform on stages—microfluidics. Our wiki followed every effort they made and would give you the most detailed report of this star-making process.

Forming the Glee

To be a good glee, first it needs a good song. The most intriguing song on earth is called OSCILLATION. If you look about, you will find it ubiquitous and extremely useful. After we taught each member this song, we need to help them sing it together, so oscillation became SYNCHRONIZED OSCILLATION. Thus how we form a glee!

Oscillation: The Magic Song of World

Once upon the time, there was a magic song called oscillation, it permeated every corner of the world. It regulated nearly everything on the earth. The interaction of moon and ocean generated the magnificent tide oscillation, and the biological process that displays a 24-hour oscillation inside human body.

Fig. 1-1 The Tides depend on several factors, including where the sun and moon are relative to the Earth	Fig. 1-2 The circadian clock inside human body

Fig. 1-3 Helium-Neon laser demonstration at the Kastler-Brossel Laboratory at Paris VI: Pierre et Marie

Besides, oscillation also plays an important part in signal transition. Take lasers for example, which are known for their intensity and can be focused to a tight spot over long distance. These characteristics all owe to their spatial coherent in the frequency of the light source.

Oscillation in Bacteria

Synthetic biologists have done a lot of work to teach bacteria to sing this oscillation song by building artificial genetic circuit inside them, since oscillations can lead to fantastic applications and benefit our everyday life. Besides regulation and signal transmission, oscillations in living organisms can also react to its growing environment, which probably will activate the trigger of oscillation inside cells and generate oscillation signals. From collected signals we can tell how an environment factor influences the cells behavior, and in turn the environment factor can be indicated by the signals. Furthermore, if we interpret these kinds of oscillation signals like 1010 in binary system, then we could even make an electronic environmental factor detector, using signals from environment as an input, and numbers on computer screen as output (Fig. 1-4).

Fig. 1-4 How to make a signal converter

Here is the progress of artificial synthetic biological oscillations have made.
In the first generation of oscillation, three transcriptional repressor systems that are not part of any natural biological clock are used to build an oscillating network, termed the repressilator, in Escherichia coli (Fig. 1-5). The network periodically induces the synthesis of green fluorescent protein as a readout of its state in individual cells. However, plasmids can hardly pass from generation to generation and this artificial clock is not robust enough and always displays noisy behavior.

Fig. 1-5 The first generation oscillator, known as repressor

Scientists constructed the second generation oscillator rapidly. This improved oscillator is fast, robust and persistent; with tunable oscillatory periods as fast as 13 min (Fig.1-6). The oscillator is designed using a previously modeled network architecture comprising linked positive and negative feedback loops. But this circuit could only monitor oscillations in individual cells through multiple cycles, which means the song is still limited to single individual.

Fig. 1-6 2nd generation of oscillation consists of positive and negative feedback loops

Thinking that singing alone is lonely, scientists introduce quorum sensing to connect isolated cells and let them sing together, and technically it's called synchronized oscillation. The synchronization effect of quorum sensing, however, is limited to over tens of micrometer (Fig.1-7). If the synchronized colony could be enlarged, then the oscillation signal will be much stronger and steadier. Longer ranged synchronized oscillation is realized by a gas-phase redox signal H₂O₂ to the third generation circuit, which could achieve the communication among colonies at over millimeter scales and became the fourth generation. Oh yeah, finally our bacteria can sing the same oscillation at the same time, so they decided to form their own glee!

Fig.1-7 3rd generation involved in quorum sensing

That's how our little E. coli friend formed their glee, a long but cheerful story. Thanks to hardworking synthetic biologists. Let's go and see how this fourth generation oscillation glee functions inside in THREE PLASMIDS!

Reference
1. http://en.wikipedia.org/wiki/Oscillation
2. Elowitz M. B. & Leibler S. A synthetic oscillatory network of transcriptional regulators. Nature 403, 335-338 (2000)
3. Stricker J. et al. A fast, robust and tunable synthetic gene oscillator. Nature 456, 516-519 (2008)
4. Danino T., Mondrago´n-Palomino O., Tsimring L. & Hasty J. A synchronized quorum of genetic clocks. Nature 463, 326-330 (2010)