Although scientists may not have come close to cataloging all the different kinds of life on the planet, genetics pioneer Craig Venter is pressing ahead with his plans to create biology version 2.0. Venter is at the forefront of the new field of synthetic biology, in which scientists try to create all new organisms out of their component genetic parts: “We’re moving from reading the genetic code to writing it” [Pittsburgh Post-Gazette], Venter has said. Now, he and his colleagues have taken the next step towards synthetic life.
In a study published in Science, the researchers explain how they took the genome from the bacterium Mycoplasma mycoides and transferred it to a yeast cell, where established genetic engineering techniques allow for easier tinkering. After altering the genome in several key ways, they transplanted it into the hollowed out shell of a different bacterial species, Mycoplasma capricolum. The breakthrough came when the altered genome “booted up” and began instructing its host bacterium to produce colonies of M. mycoides.
That success will help researchers overcome a stubborn obstacle that has prevented the creation of a made-from-scratch life form. Last year, Venter’s team created a synthetic bacterial genome by stitching together pieces of synthesized DNA. To build a synthetic organism, however, researchers will have to transplant that synthetic genome into a cell and have it successfully reboot the cell. But that last step has proved problematic. The synthetic genome was assembled in yeast, which means it lacked some of the molecular markings characteristic of bacteria. Researchers discovered that without those markings, the host bacterium viewed the transplanted genome as a foreign invader and destroyed it [Technology Review]. In the new study, the researchers added chemical markings called methyl tags to the M. mycoides genome while it was in the yeast cell, permitting the genome to sneak past the host bacterium’s defenses.
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How life evolved from a mix of chemicals on the young planet Earth is one of science’s most enduring mysteries, which biochemists are attempting to solve by recreating the earliest building blocks of life in the laboratory.
Earth’s biology is based on DNA, which carries all an organism’s genetic information in a molecule that takes the shape of a spiraling ladder. RNA, the molecule that facilitates protein manufacturing, has a simpler shape–it’s a single strand, as opposed to DNA’s double strand–leading some biologists to propose the RNA world hypothesis in which RNA evolved first and eventually gave rise to DNA. But trying to imagine the assembly of RNA from its chemical components poses its own problems. How could RNA, which encodes proteins, first form, when proteins are needed for [its] synthesis? Now, scientists report that they’ve cooked up molecular hybrids of proteins and nucleic acids that skirt the dreaded paradox [ScienceNOW Daily News].
The hybrids they created could resemble the precursors to RNA, researchers report in Science. “It’s the pre-RNA world. There’s a hypothesis that says RNA is so complicated, it couldn’t have arisen de novo” — from scratch — “on early Earth,” said study co-author Luke Leman…. “So you need some more primitive genetic system that nature fiddled around with and finally decided to evolve into RNA” [Wired.com].
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In a masterful work of “DNA origami,” researchers have created a nanoscale DNA “box” which can be opened with DNA “keys”. One day, such structures could be filled with drugs, injected into the blood, and then unlocked when and where the drugs are required [New Scientist]. Researchers say the boxes could also be used as minuscule environmental sensors that open or close in response to a stimulus, or as the logic gates of a DNA-based computer.
To accomplish this feat, described in a paper in Nature, researchers exploited the fact that complementary DNA bases–the fundamental building blocks of DNA’s double helix–attach to each other. To design the box, the researchers developed a computer program to generate a continuous single-stranded DNA sequence that, along with smaller DNA fragments that act as staples, would self-assemble into the desired shape. The sequence was devised with many complementary regions so that it would automatically fold into six roughly square accordion-like sheets–the sides of the box–based on DNA’s natural tendency to pair into double strands. The DNA staples, also driven by the pairing of complementary sequences, stitched the sheets’ edges together to form a hollow cube with a hinged lid [Technology Review]. The final product was a box that measured 42 by 36 by 36 nanometers, and had a cavity big enough to hold enzymes or virus particles.
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In an important step towards creating synthetic life forms, genetics pioneer George Church has produced a man-made version of the part of the cell that turns out proteins, which carry out the business of life. “If you going to make synthetic life that is anything like current life … you have got to have this … biological machine,” Church told reporters in a telephone briefing. And it can have important industrial uses, especially for manufacturing drugs and proteins not found in nature [Reuters].
Church’s team built a functional ribosome from scratch, molecule by molecule. Ribosomes are molecular machines that read strands of RNA and translate the genetic code into proteins. They are exquisitely complex, and previous attempts to reconstitute a ribosome from its constituent parts – dozens of proteins along with several molecules of RNA – yielded poorly functional ribosomes, and even then succeeded only when researchers resorted to “strange conditions” that did not recapitulate the environment of a living cell, Church said [Nature blog]. Next, the researchers want to produce man-made ribosomes that can replicate themselves.
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In an important step towards the creation of artificial life, scientists in Florida announced this week they have created a synthetic form of DNA that, with a catalyst, can replicate itself. The breakthrough moves biochemist Steven A. Benner closer to achieving what he calls “Darwinian evolution in a test tube” [Seed Magazine].
Benner’s artificial genetic system comprises four nucleotides—building blocks of DNA—seen in humans, plus eight extra nucleotides he created by altering the human versions. He got the synthetic DNA to reproduce using the polymerase chain reaction, a common tool of molecular biology whereby an enzyme triggers the duplication of genetic material; natural DNA, in contrast, can replicate on its own. Once the synthetic form can self-replicate, said Benner, “then it’s artificial life” [LiveScience].
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Researchers have created a “biocomputer” out of strands of RNA inside a living yeast cell, and demonstrated that it can be programmed to respond to conditions within the cell by taking specific actions. Like the most basic computers, the RNA device operates on a simple system of Boolean logic—it can be programmed to respond to the commands AND, OR, NAND and NOR.
The invention could have a wide range of applications, researchers say. Bio-computers might eventually serve as brains for producing biofuels from cells, for example, or to control “smart drugs” that medicate only under certain conditions. For example, a smart drug could sample a cellular environment and trigger a self-destruct sequence if disease is detected, [study coauthor Christina] Smolke said [National Geographic News].
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