2009 Hamilton Award Lectureship
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2009 Hamilton Award – An Expanding Genetic Code
In this 2009 Hamilton Award Lecture, Professor Peter G. Schultz of The Scripps Research Institute (TSRI) describes his group's pioneering work on unnatural amino acid mutagenesis. The story begins with the observation that, on the one hand, through natural selection, Nature has settled upon about 20 amino acids as suitable building blocks for proteins. On the other, synthetic organic chemists have the power to synthesize many "non-proteinogenic" amino acids in the laboratory, and equip these with a variety of useful functional groups, as molecular beacons, binding handles, molecular switches, etc. Schultz and his co-workers have successfully re-engineered protein synthesis so that such non-proteinogenic amino acids can be surgically inserted into specific positions in native proteins, thereby creating a powerful tool for synthetic biology. The talk goes on to explain how this has been accomplished by engineering into the cell an orthogonal tRNA-synthetase-suppressor tRNA pair, to charge and incorporate the unnatural amino acid(s) of interest. Useful applications of this enabling technology are delineated, from protein tagging with artificial fluorophores, to the installation of metal-binding sites, to the study of post-translational modification (e.g. phosphorylation, sulfation) to the study of signal transduction via photo-switching (photocaged serines, photo-induced protein cleavage).
