Institute for Systems Genetics
NYU Langone Medical Center
Host: Dr. Songtao Jia
Title: "Building synthetic chromosomes from scratch"
Abstract: Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. They have also enabled the construction of novel genetic pathways and genomic elements, furthering our understanding of systems-level phenomena. Our current understanding of genomics is solidly within the experimental phase, yet genome engineering is in its infancy. The synthetic yeast genome project, Sc2.0 is well on its way with several of the first synthetic Saccharomyces cerevisiae chromosomes completed. Undergraduate students provide a workforce for synthesis and assembly for some of these chromosomes, though a wide variety of assembly schemes are employed by the various groups building chromosomes. The synthetic genome features several systemic modifications, including TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, tRNA genes, transposons and silent mating loci as well as strategically placed loxPsym sites to enable genome scrambling using an inducible evolution system termed SCRaMbLE (Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution). SCRaMbLE can be used as a novel method of mutagenesis, capable of generating complex genotypes and a variety of phenotypes. The fully synthetic yeast genome will open the door to a new type of combinatorial genetics based on variations in gene content and copy number, rather than base changes. We also describe supernumerary designer “neochromosomes” that add new functionalities to cells such as humanized pathways.
Dymond et al. Synthetic chromosome arms function in yeast and generate phenotypic diversity by design. Nature, 477:471-6. 2011.
Annaluru et al. Total synthesis of a functional designer eukaryotic chromosome. Science. 2014 344:55-8. 2014.