Scientists 'Boot Up' a Bacterial Cell With a Synthetic Genome

Scientists have developed the first cell controlled by a synthetic genome. They now hope to use this method to probe the basic machinery of life and to engineer bacteria specially designed to solve environmental or energy problems.

Scanning electron micrographs of M. mycoides JCVI-syn1. Samples were post-fixed in osmium tetroxide, dehydrated and critical point dried with CO2 , then visualized using a Hitachi SU6600 scanning electron microscope at 2.0 keV.

The study will be published online by the journal Science, at the Science Express website, on May 20.
The research team, led by Craig Venter of the J. Craig Venter Institute, has already chemically synthesized a bacterial genome, and it has transplanted the genome of one bacterium to another. Now, the scientists have put both methods together, to create what they call a "synthetic cell," although only its genome is synthetic.
"This is the first synthetic cell that's been made, and we call it synthetic because the cell is totally derived from a synthetic chromosome, made with four bottles of chemicals on a chemical synthesizer, starting with information in a computer," said Venter.
"This becomes a very powerful tool for trying to design what we want biology to do. We have a wide range of applications [in mind]," he said.
For example, the researchers are planning to design algae that can capture carbon dioxide and make new hydrocarbons that could go into refineries. They are also working on ways to speed up vaccine production. Making new chemicals or food ingredients and cleaning up water are other possible benefits, according to Venter.
In the Science study, the researchers synthesized the genome of the bacterium M. mycoides and added DNA sequences that "watermark" the genome to distinguish it from a natural one.
Because current machines can only assemble relatively short strings of DNA letters at a time, the researchers inserted the shorter sequences into yeast, whose DNA-repair enzymes linked the strings together. They then transferred the medium-sized strings into E. coli and back into yeast. After three rounds of assembly, the researchers had produced a genome over a million base pairs long.
The scientists then transplanted the synthetic M. mycoides genome into another type of bacteria, Mycoplasm capricolum. The new genome "booted up" the recipient cells. Although fourteen genes were deleted or disrupted in the transplant bacteria, they still looked like normal M. mycoides bacteria and produced only M. mycoides proteins, the authors report.
"This is an important step we think, both scientifically and philosophically. It's certainly changed my views of the definitions of life and how life works," Venter said.
Acknowledging the ethical discussion about synthetic biology research, Venter explained that his team asked for a bioethical review in the late 1990s and has participated in variety of discussions on the topic.
"I think this is the first incidence in science where the extensive bioethical review took place before the experiments were done. It's part of an ongoing process that we've been driving, trying to make sure that the science proceeds in an ethical fashion, that we're being thoughtful about what we do and looking forward to the implications to the future," he said.
This research was funded by Synthetic Genomics, Inc. Three of the authors and the J. Craig Venter Institute hold Synthetic Genomics, Inc. stock. The J. Craig Venter Institute has filed patent applications on some of the techniques described in this paper.

How Ducks Host Influenza Unharmed: Could Findings Shield Humans from Bird Flu Viruses?

A University of Alberta-led research team has discovered an influenza detector gene that could potentially prevent the transmission of the virus to humans.

Mallard duck with fifteen ducklings. Researchers have identified the genetic detector that allows ducks to live, unharmed, as the host of influenza. 

Katharine Magor, a U of A associate professor of biology, has identified the genetic detector that allows ducks to live, unharmed, as the host of influenza. The duck's virus detector gene, called retinoic acid inducible gene -- I, or RIG-I, enables a duck's immune system to contain the virus, which typically spreads from ducks to chickens, where it mutates and can evolve to be a human threat like the H5N1 influenza virus. The first human H5N1 cases were in Hong Kong in 1997. Eighteen people with close contact to chickens became infected and six died.
Magor's research shows chickens do not have a RIG-I gene. A healthy chicken can die within 18 hours after infection, but researchers have successfully transferred the RIG-I gene from ducks to chicken cells. The chicken's defenses against influenza were augmented and RIG-I reduced viral replication by half.
One potential application of this research could affect the worldwide poultry industry by production of an influenza-resistant chicken created by transgenesis.
The work of Katharine Magor, her U of A PhD candidate Megan Barber, and researchers from the United States (Jerry Aldridge and Robert Webster) was published March 22, in the online, early edition of Proceedings from the National Academy of Sciences.

Life on Saturn's Moon Titan: Stand Well Back and Hold Your Nose!

Research by astrobiologist William Bains suggests that if life has evolved on the frozen surface of Saturn's moon, Titan, it would be strange, smelly and explosive compared to life on Earth.

Dr Bains will present his work at the National Astronomy Meeting in Glasgow on April 13.
"Hollywood would have problems with these aliens" says Dr. Bains. "Beam one onto the Starship Enterprise and it would boil and then burst into flames, and the fumes would kill everyone in range. Even a tiny whiff of its breath would smell unbelievably horrible. But I think it is all the more interesting for that reason. Wouldn't it be sad if the most alien things we found in the galaxy were just like us, but blue and with tails?"
Dr Bains, whose research is carried out through Rufus Scientific in Cambridge, UK, and MIT in the USA, is seeking to work out just how extreme the chemistry of life can be. Life on Titan, Saturn's largest moon, represents one of the more bizarre scenarios being studied. Titan is twice as large as our Moon and has a thick atmosphere of frozen, orange smog. At ten times our distance from the Sun, it is a frigid place, with a surface temperature of -180 degrees Celsius. Water is permanently frozen into ice and the only liquid available is liquid methane and ethane, which the Cassini/Huygens mission has shown is present in ponds and lakes on the surface of the moon.
"Life needs a liquid; even the driest desert plant on Earth needs water for its metabolism to work. So, if life were to exist on Titan, it must have blood based on liquid methane, not water. That means its whole chemistry is radically different. The molecules must be made of a wider variety of elements than we use, but put together in smaller molecules. It would also be much more chemically reactive," said Dr Bains.
The solubility of chemicals in liquid methane is very limited, and strongly dependent on molecular weight. With a few exceptions, molecules with more than 6 heavy (non-hydrogen) atoms are essentially insoluble. So a metabolism running in liquid methane will have to be built of smaller molecules than terrestrial biochemistry, which is typically built of modules of around 10 heavy atoms. However you can only build around 3400 molecules from such a small number of atoms if you are limited to the chemistry that terrestrial life uses i.e. carbon, nitrogen, oxygen, and sulphur and phosphorus in very limited chemical contexts.
Dr Bains explained, "Terrestrial life uses about 700 molecules, but to find the right 700 there is reason to suppose that you need to be able to make 10 million or more. The issue is not how many molecules you can make, but whether you can make the collection you need to assemble a metabolism. It is like trying to find bits of wood in a lumber-yard to make a table. In theory you only need 5. But you may have a lumber-yard full of offcuts and still not find exactly the right five that fit together. So you need the potential to make many more molecules than you actually need. Thus the 6-atom chemicals on Titan would have to include much more diverse bond types and probably more diverse elements, including sulphur and phosphorus in much more diverse and (to us) unstable forms, and other elements such as silicon."
Energy is another factor that would affect the type of life that could evolve on Titan. With Sunlight a tenth of a percent as intense on Titan's surface as on the surface of Earth, energy is likely to be in short supply.
"Rapid movement or growth needs a lot of energy, so slow-growing, lichen-like organisms are possible in theory, but velociraptors are pretty much ruled out," said Bains.