Synthetic Biology facility at the MRC Laboratory of Molecular Biology

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Living cells have genes made of DNA. DNA is a molecule comprising a string of bases of four different types, and the sequence of these bases in a gene directs the synthesis of a particular protein, which consists of a string of amino acids of twenty different types. Three bases encode one amino acid, this code being read by a cellular machine, the ribosome, which makes the protein. Some triplets do not encode amino acids, but act as stop signals. It is possible to engineer cells such that one of these stop triplets instead encodes a synthetic amino acid, which can have novel chemical properties. Genes can be chemically synthesised with any sequence, so by introducing the appropriate triplet proteins can be specified that have novel properties, such as an enzyme that can be turned on by light. Synthetic biology also allows the creation of new kinds of ribosome in bacteria, engineered to translate only particular synthetic genes, which can read four bases at a time instead of three, thus significantly expanding the range of new amino acids that can be encoded. This technology not only makes possible a wide range of experiments to study the functions of cells and organisms, but also allows the production of novel proteins for therapeutic or other use, such as antibodies with drugs attached at specific sites. Ultimately, such engineering could produce entirely new encoded polymers with many potential uses.DNA too can be altered in novel ways. By engineering the enzymes that copy DNA, it is possible to produce, in the test tube, "XNA" molecules that retain the double helical structure of DNA but are made from chemically different precursors, and hence have a different chemical structure that is resistant to natural and chemical degradation, and can have other novel properties. By making billions of variants of a short sequence of bases, one can select molecules that have a desirable property, such as inhibiting an enzyme or catalysing a reaction, copy them into DNA, and identify the particular sequence. These molecules can be chemically synthesised, and used as potential drugs or for many other purposes.The development of these technologies depends on the synthesis of novel DNA sequences and genes, and many sophisticated forms of analysis including mass spectrometry and advanced microscopy to determine the properties of the novel proteins and XNA molecules that result, and their effects on cells and organisms. This award will provide the advanced equipment required to automate gene synthesis, engineer new functions, and test the many different applications of the new technology.