The Build-A-Genome (B-A-G) Course was introduced in 2007, and is now offered for up to 20 students each semester and during the summer. To date, about 200 students have completed the course, including students majoring in computer science, biomedical engineering, biology, chemical and bio-molecular engineering, and biophysics. Entering students are interviewed to evaluate their understanding of the Polymerase Chain Reaction (PCR), DNA cloning and sequencing, nucleic acid structure, biopolymer synthesis, and more before acceptance. The students, ranging from high school students to grad students and the occasional postdoc (but >95% undergraduate) master not only methodology, but also fundamentals of molecular and synthetic biology, related computational skills (there is also a specialized computational track in the course), as well as exposure to the economic / entrepreneurial and bioethics sides of synthetic biology. Following a biotechnology “boot-camp,” students are given round-the-clock access to computational and wet-lab resources and are expected to invest 15 to 20 hours per week in this four-credit course. Each student is assigned a segment of the synthetic yeast genome, and must deliver 100% accurate DNA by the end of the semester. This remarkable course, unlike any other in the world, has been called a “cross between a one-room schoolhouse and a biotech company.” See Dymond et al. Genetics, 181: 13-21.
Over seven years the workflow in the B-A-G class has changed to accommodate the needs of the project as well as the decreasing cost of commercial DNA synthesis. The first B-A-G workflow (2007-2012) specified the assembly of ~750bp ‘building blocks’ from overlapping 60-79mer oligonucleotides by polymerase chain assembly. Here, students were assigned 13-15 building blocks, corresponding to ~10,000bp of synthetic DNA, and were asked to submit sequence verified, subcloned constructs at the end of the semester. With the decreasing cost of DNA synthesis, however, the commercial production of synthetic DNA in this size range became more cost effective in late 2012. Thus, the Spring 2013 B-A-G class at Johns Hopkins University undertook a new workflow to build ‘minichunks’, or ~3kb segments of synthetic DNA, from building blocks previously constructed in B-A-G or delivered from a synthesis company. In this workflow, students use ‘in yeasto’ assembly, exploiting the native homologous recombination machinery in yeast for minichunk assembly. The minichunk assembly protocol was developed in collaboration with students of the Tianjin University “B-A-G China” course. Notably, the cost per base pair for minichunk assembly is <10 cents using our protocol (taking into account only the cost of reagents and considering labor to be free!). Now in the spring semester of 2014 B-A-G students at Hopkins are building ~10kb chunks from minichunks, also using yeast homologous recombination as a cloning tool.