Genome engineering: writing a better genome

At first glance, the undergraduate biology curriculum at the Johns Hopkins University doesn't look all that different from other biology programs. All the usual suspects are on the schedule: General Biology and Cell Biology, Virology and Genetics, Immunology and Biochemistry. But down at the bottom of that list is something that you don't see every day — Biology 420: Build-a-Genome. While the course might sound like the molecular equivalent of a certain mall-based ursine construction boutique, Build-a-Genome is serious science. The practical portion of the course involves reconstructing a yeast chromosome, base by base, from chemical building blocks. It's part of a larger research effort known as Synthetic Yeast 2.0 (Sc2.0), a project that seeks to reconstruct and redesign the entire yeast genome, all 12 million nucleotides of it. Sc, or Saccharomyces cerevisiae, " has an ancient industrial relationship with humans which is alive and well today in the form not just of bread and beer but pharmaceuticals like artemisinin, biofuels, and lots of other specialty items, " notes Jef Boeke, a yeast geneticist and director of the High-who leads the Sc2.0 effort. Boeke and his colleagues, computational biologist Joel Bader and molecular biologist Srinivasan Chandrasegaran, realized that, useful as brewers' yeast is, it could potentially be made even more so, biotechnologically speaking. Boeke and his team decided to give it a try. Very quickly, though, they realized there was a problem: The yeast genome is big, and DNA synthesis is slow. " While I was waiting 11 months for my DNA to be delivered by Codon Devices, I was wondering, how am I going to make the other 99% of the genome? At this rate I'll be dead long before I get there, " recalls Boeke. " And then it hit me — we have all these undergrad students across town who were looking for a research experience, and we could give them an excellent one. " Enter Build-a-Genome. Each semester 15-20 students — mostly undergrads but also the occasional high school student, graduate student, and even professor — take charge of their own 10,000-nucleotide slice of S. cerevisiae chromosome III, building up chunks of synthetic material from smaller 750-base pair fragments. " Students were remarkably efficient in the synthesis of these building blocks, and the first pass of the entire ~280 kb synthetic chromosome III sequence was achieved in one academic year (one summer session, two semesters, and …