Introduction
We are entering a new world, the world of synthetic biology. It could provide more effective therapies, cheaper medicines, easily recyclable new materials, biofuels, bacteria able to degrade toxic substances from the environment.
Synthetic biology is a fast moving field. It is defined as the rational engineering of biology, aiming to design new biological systems. Synthetic biology will advance our knowledge of living organisms and will develop many industrial applications in the area of health, energy, materials, environment and agriculture.
The current achievements of synthetic biology include a diagnosis system able to monitor annually some 400 000 AIDS or hepatitis patients and the synthesis of artemisinin, a highly effective anti-malarial drug.
News - Synthia Project
On May 20, 2010, after 15 years of work and $40 million investment, a 20-person team from the J. Craig Venter Institute created the first artificially controlled bacterial chromosome.
The team replaced the natural genome of Mycoplasma capricolum, a bacterium that can produce pneumonia in goats, by a nearly identical genome but synthesized in the laboratory. This genome is a single chromosome of about 1.155 million base pairs, which had previously been decrypted and the information stored in databases.
From this information, containing the base pair sequence, the artificial chromosome has been synthesized. This was only slightly modified by a "filigrame", which allows to be distinguished from the natural chromosome.
First, more than 1000 sequences of about 1000 base pairs were produced by chemical synthesis. Then, the fragments were assembled in several stages, some of them by biotechnological methods involving the bacterium Escherichia coli or yeast.
After removing the restriction enzymes (proteins that cut DNA) in a natural bacterium Mycoplasma capricolum, the scientists transferred the artificial chromosome into it. It took many attempts to make the synthetic DNA replicate and the natural DNA disappears - probably destroyed by the restriction enzymes of the synthetic DNA. Moreover, these modified cells called "Synthia", have replicated and expanded. They were also able to transcribe their genes into RNA and translate them into proteins. Their structure and behavior are identical to those of natural bacteria.
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Synthia cell colonies (bottom), seen by electron microscopy (top) and their genome map (right). |
However, this is not a synthetic bacterium but only a bacterium controlled by a synthetic genome assembled from fragments of synthesized DNA. The cytoplasm is part of the original host cell. This is equivalent to changing the hard drive of a computer and put in a new operating system.
The next step is to design bacteria controlled by a genome of 2 million base pairs, which allows applications in biotechnology: cells able to synthesize medicines, clean the soil or produce biofuel from non-food biomass.
News - Synchronization of transcriptional regulators of E. Coli
In January 2010 a team of scientists from the University of California at San Diego was able to synchronize the molecular clocks of a colony of bacteria.
Ten years ago, using techniques of synthetic biology, researchers created artificial clocks in individual Escherichia coli bacteria. This time the clocks were not only built but also synchronized in a colony of bacteria.
Bacteria can synchronize the expression of some of their genes by a mechanism called quorum sensing: they communicate with each other by chemical messengers that provide information on the population density of their species or other species, which sometimes allows them to have symbiotic behavior. One of the chemical messengers is acyl-homoserine lactone (AHL), a small molecule that easily diffuses across cell membranes.
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Escherichia coli bacteria (right) were modified to get artificial clocks synchronized (top left) and to highlight their oscillations (bottom left). |
Using components of Vibrio fischeri, a luminescent bacterium of seawater, and Bacillus thuringiensis, that lives in the soil or water, scientists designed a system where the AHL molecule is involved in the expression of two genes: one produces an enzyme that catalyzes the synthesis of AHL, the other another enzyme that degrades the AHL. These loop actions are antagonists, therefore they generate oscillations of the AHL concentration. A third gene expressing a green-fluorescent protein was coupled to this mechanism in order to view these oscillations.
The dual role of the AHL - activation of genes producing the oscillations and messenger between cells - allows clock synchronization in a colony of bacteria, so that all its members "flash" in unison.
This research could help the understanding of sleep-wake cycles and diffusion rates of hormones in the body and find applications for the treatment of sleep disorders and seizures.
Another possibility is to develop cellular implants that can produce specific and precise doses of hormones like insulin or other therapeutic proteins. The patients will no longer have to remember that they must take medication at set times.
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