Radical genome recoding paves way for new era in the manipulation of

first_imgThere’s a lot of hyperbole in science journalism, or at least a tendency to state every finding in its most extreme possible form, so let’s be clear: the following story is incredible, a fundamental step forward for the human animal and its ability to control the environment in which it lives.This isn’t an over-blown test tube victory unlikely to generalize to humans; this is a proof of concept for a whole new era in the manipulation of life. In two concurrent studies published last week in the journal Science, researchers recoded the genomes of e. coli colonies to begin to use building blocks never before seen by living things.Proteins, the main functional units of the cell, are made of up of various combinations of 20 basic amino acids. Since DNA uses a four-letter system to code for these amino acids, basic math can show us why life was forced to use DNA words (or “codons”) three letters in length: One letter can code for four different states, two letters for (4*4 = 16) different states, and three letters for (4*4*4 = 64) different states. Two letters isn’t quite enough, but three provides many more possible words than the 20 we technically require.The genetic code. Notice how many amino acids can arise from more than one 3-letter codon.As a result the body has what are called “degenerate codons,” meaning that two different codons could both lead to the same final amino acid. In the first of these two studies, researchers replaced the codon UAG, which normally acts as a “STOP” signal that marks the end of protein synthesis, with the codon UAA. UAA serves the same STOP function as UAG, which basically means that the researchers can remove the STOP functionality from UAG codons without harming the cell. They have freed up one out of the cell’s 64 words with little or no impact on that cell’s ability to survive.These genetically recoded organisms (or GROs) now have a word free — but there’s no need to stop at just one. The second of the two studies looked to test the bacteria’s ability to soak up multiple recodings, choosing 13 different codons to replace with degenerate versions. The results were incredible, as even with 24% of the relevant DNA replaced, the proteins of interest were still made without trouble. That’s a full fifth of the protein vocabulary now open for some alternate use, and the possibilities are nearly endless.Non-Standard Amino Acids (NSAAs) can now be incorporated into proteins by inserting new instances of the hijacked codons. In the first study, any time the researchers inserted the former STOP codon UAG, the cell incorporated their new UAG NSAA into the growing strand. This means they’ve expanded the protein alphabet from 20 amino acids to 21. Beyond any possible uses for this extra building block, it turns out that such changes to biochemistry can have benefits in and of themselves.Radical recoding boiled down to its bare essentials.Even just a single codon replacement made the colony of the first study much more resistant to viral infection. Viruses generally work by hijacking a cell’s machinery to make more copies of the virus, and so their life cycle depends on finding predictable genetic mechanisms with which to work. Changing the meaning of codons and substituting NSAAs fundamentally hampers the main mechanism of viral replication. This could make industrial bacterial colonies, which will only become more important as time goes on, all but invulnerable to the sorts of catastrophic viral invasions that currently keep industrial biologists awake at night.The NSAAs themselves could allow amazing new advances, as well. More durable versions of amino acids, or novel stabilizing molecules, could lead to drugs that survive longer in the body, or which have much longer expiration dates than today’s versions. Totally new lock-and-key molecules could be added to make sure a drug can’t be delivered to the wrong part of the body. Stretches of a suicide molecule could let scientists destroy just a single type of engineered protein at will.This is the first time we have managed to successfully monkey with the genetic code itself, completely redefine a DNA word across an entire genome. It’s an important step forward for synthetic biology, and a powerful research method that is certain to prompt many a Geek article still to come.last_img read more

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