Jason Chin, MRC and Cambridge University
"Repgoramming the Genetic Code"
In the cell, DNA is copied to messenger RNA, and triplet codons (64) in the messenger RNA are decoded - in the process of translation - to synthesize polymers of the natural 20 amino acids. This process (DNA-RNA-protein) describes the central dogma of molecular biology and is conserved in terrestrial life. We are interested in re-writing the central dogma to create organisms that synthesize proteins containing unnatural amino acids and polymers composed of monomer building blocks beyond the 20 natural amino acids. This seminar will discuss our invention and synthetic evolution of new 'orthogonal' translational components (including ribosomes and aminoacyl-tRNA synthetases) and the assembly of these components into an ‘orthogonal translation pathway’ to address the major challenges in re-writing the central dogma of biology.
Dr. Chin will discuss the application of the approaches developed for incorporating unnatural amino acids into proteins. He will describe i) the development and application of approaches to genetically install post-translational modificationsincluding ubiquitnation, acetylation and methylation into proteins, and the application of these approaches to obtain new insight into biological regulation, ii) approaches to photo-control protein function, including catalytic activity, in mammalian cells and the development of a strategy to dissect the contributions of elementary steps and feedback regulation to signalling cascades, iii) the development of rapid methods for site-specifically labelling proteins in cells with small molecule fluorophores for live cell imaging, and iv) the extension of genetic code expansion approaches from E.coli to yeast to mammalian cells and, most recently, to whole animals (C.elegans and D. melanogaster), with the goal of applying the tools we have developed for manipulating and imaging processes in cell culture to processes best studies at the level of whole organisms.
