A powerful set of molecular tools helps synthetic biologists to assemble DNA of different sizes, from the gene to the chromosome scale. The yeast Saccharomyces cerevisiae is the focus of a project to synthesize one of the first non-bacterial artificial genomes. Leslie Mitchell had no intention of doing a postdoc. After completing her PhD at the University of Ottawa, she had planned to move to industry. But then a member of her thesis committee, geneticist Jef Boeke, invited her to join his team at Johns Hopkins University in Baltimore, Maryland. Boeke was spearheading an ambitious effort to design and build an entire yeast genome from scratch, known as the Sc2.0 project. It was a once-in-a-lifetime opportunity, and one she just couldn’t refuse. “I just thought that was the coolest way to study biology and really understand it,” she says. “To build it from the ground up.” Eight years later, the Boeke lab (now at New York University’s Langone Medical Center in New York City) and its collaborators in Europe, Asia and Australia are close to producing recoded versions of all 16 Saccharomyces cerevisiae chromosomes, as well as a 17th, artificial, ‘neochromosome’.