Synthetic biologists prepare to leap through the looking glass

At a meeting last weekend featuring Harvard University’s Origins of Life Initiative, synthetic biologist/systems biologist/sequencing guru/technobiology polymath George Church announced that his lab had taken an important step towards the creation of synthetic life by assembling a functional ribosome.

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.

In addition to applications in synthetic biology, creating a synthetic ribosome could improve industrial methods for making proteins without relying on cells. Having a tailor-made ribosome could also make it easier to chemically label proteins in situations where researchers don’t want to label the entire cell and all proteins in it.

And for Church, making a ribosome is a critical step in one of his pet projects: creating a “mirror image cell" by altering the stereochemistry of the molecules within.


In a mirror image cell, proteins that would normally be made of left-handed amino acids would instead contain right-handed amino acids, and may no longer be subject to degradation by enzymes found in the natural environment. (To read more on Church’s scheme, check out this transcript and video of a 2007 meeting in which he discusses the project. And for a discussion on the safety aspects of mirror cells, check out Bloomberg’s article on the ribosome work.)

Church’s lab hasn’t yet tried to create mirror image proteins. Michael Jewett, a postdoc in the lab, began with ribosomes isolated from living bacteria, broke those ribosomes down into their separate pieces, and then found conditions in which those pieces would spontaneously reassemble into ribosomes. So far he’s only tried one variation on the natural mix: substituting a new RNA molecule for one of the ones found in the original ribosome, and coaxing the ribosome into making a fluorescent protein called luciferase.

Jumping through the looking glass is still a few steps down the line, but Church feels that his lab is well on its way. “This is not a mirror cell yet,” he said. “But even though it’s just a milestone and there are many other steps to do … we’ve completed what I had thought would be two of the hardest steps.”

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