The Ellington lab is attempting to develop novel synthetic organisms based on altering the translation apparatus and developing modular nucleic acid software. Translation engineering centers on the introduction of novel amino acids into proteins that have the capability to base-pair, and is being pursued using a variety of techniques, including directed evolution, computational design, and high-throughput synthesis. This latter capacity is abetted by a Gene Synthesis Facility capable of producing multiple kilobases of DNA per week. In parallel, DNA circuits based on strand exchange reactions and capable of executing embedded algorithms are being developed, using tools such as aptamers and DNA nanotechnology. The first application of these circuits will be in point-of-care diagnostics, but eventually these circuits should form the basis of a new, modular cellular operating system. We anticipate this operating system should also prove useful in cell-to-cell communication and drug delivery in organisms, and are actively pursuing in vivo studies. In order to enhance both engineering translation and installing DNA circuitry into cells, we have developed tools to directly synthesize operons, enable facile horizontal transfer, and edit genomes, and are interested in how such tools can be used to engineer cellular consortiums, including biofilms.
