We are Denis Malyshev (/u/danmalysh), Kiran Dhami (/u/kdhami), Thomas Lavergne (/u/ThomasLav), Yorke Zhang (/u/yorkezhang), Elie Diner (/u/ediner), Aaron Feldman (/u/AaronFeldman), Brian Lamb (/u/technikat), and Floyd Romesberg (/u/fromesberg), past and present members of the Romesberg Lab that recently published the paper A semi-synthetic organism with an expanded genetic alphabet

The Romesberg lab at The Scripps Research Institute has had a long standing interest in expanding the alphabet of life. All natural biological information is encoded within DNA as sequences of the natural letters, G, C, A, and T (also known as nucleotides). These four letters form two “base pairs:” every time there is a G in one strand, it pairs with a C in the other, and every time there is an A in one strand it pairs with a T in the other, and thus two complementary strands of DNA form the famous double stranded helix. The information encoded in the sequences of the DNA strands is ultimately retrieved as the sequences of amino acids in proteins, which directly or indirectly perform all of a cell’s functions. This way of storing information is the same in all organisms, in fact, as best we can tell, it has always been this way, all the way back to the last common ancestor of all life on earth.

Adding new letters to DNA has proven to be a challenging task: the machinery that replicates DNA, so that it may be passed on to future generations, evolved over billions of years to only recognize the four natural letters. However, over the past decade or so, we have worked to create a new pair of letters (we can call them X and Y for simplicity) that are well recognized by the replication machinery, but only in a test tube. In our recent paper, we figured out how to get X and Y into a bacterial cell, and that once they were in, the cells’ replication machinery recognized them, resulting in the first organism that stably stores increased information in its DNA.

Now that we have cells that store increased information, we are working on getting them to retrieve it in the form of proteins containing unnatural amino acids. Based on the chemical nature of the unnatural amino acids, these proteins could be tailored to have properties that are far outside the scope of natural proteins, and we hope that they might eventually find uses for society, such as new drugs for different diseases.

You can read more about our work at Nature News&Views,The Wall Street JournalThe New York TimesNPR.


May 22nd, 2014

Posted In: innovations

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