The Synthetic Yeast Genome Project - Sc2.0

Webinar: "Building a Synthetic Eukaryotic Genome" webinar presented by Sc2.0 investigator Leslie Mitchell, Ph.D.

Watch the archived webinar to learn more about the Synthetic Yeast Genome project and how you can design and engineer genes, pathways and even chromosomes using software and experimental infrastructure developed by Sc2.0.

Why build a synthetic genome? Starting from scratch gives you a chance to design the genome with valuable new features you want, and get rid of evolutionary hangers-on that you don't need. Sc2.0 aims to make chromosomes:

  • Stronger by ditching destabilizing transposons;
  • Leaner by removing sequences that appear to be 'junk';
  • More agile, through SCRaMbLE, a built-in inducible diversity generator that will accelerate the development of yeast strains optimized for practical uses, such as industrial fermentation of agricultural products into biofuels or producing medically important enzymes.

The Sc2.0 Project, led by Dr. Jef Boeke at the Johns Hopkins University, is the first attempt to synthesize a eukaryotic cell genome, that of Saccharomyces cerevisiae. The goal of the Sc2.0 Project is to synthesize the entire yeast genome - about 6,000 genes - with a built-in diversity generator that will enable researchers to discover how yeast, as a model organism, deals with genetic change and how genomes might be improved to create more robust organisms. This project lays the foundation for future work to design genomes for specific purposes, such as creating new medications or biofuels.

To facilitate gene rearrangement and genome minimization, Boeke and colleagues designed the Synthetic Chromosome Recombination and Modification by LoxP-mediated Evolution (SCRaMbLE) system. More than 5000 loxP sites will be introduced in the final genome, so that pulsatile Cre expression can create innumerable unique deletions and rearrangements. Viable genomes can be sequenced and many variant yeast strains can be studied to deduce the limits of chromosome structure, minimal eukaryotic genome structures, and gene/feature adjacency rules in genomes.

In 2011, the first designer yeast chromosome arm, synIXR, was successfully synthesized and shown to support robust yeast cell growth. To construct the remainder of the synthetic genome, incorporating SCRaMbLE and other designer features, requires DNA synthesis on an unprecedented scale. To this end, in 2012 GenScript synthesized 17 DNA fragments, each ~10 kb in length to become part of synthetic yeast chromosome VI. GenScript is proud to be a contributing partner in the Sc2.0 International Consortium whose goal is to build a designer synthetic eukaryotic genome.

Sc2.0 recently achieved a critical milestone with the completion of synthesis of the first functional eukaryotic chromosome in yeast.

  • See the Sc2.0 official webpage:  http://syntheticyeast.org/.
  • GenScript is the only commercial entity to be invited to participate in this large-scale project, and will contribute a part of Chromosome 6. See all collaborators.
  • GenScript Press Release: GenScript to Synthesize Parts of World's First Designer Yeast Genome.
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