Build-a-Genome course: Recruiting an army of undergraduates to synthesize yeast genome

Professors in colleges and universities strive to promptly bring new techniques to undergraduate classrooms. While the theory and concepts readily become part of the curriculum, the practical laboratory classes do not get much focus beyond a few protocol-based exercises. Only undergraduate students who are lucky enough to obtain internships in a research laboratory can learn and master different techniques. Jef Boeke, who is Professor in the Department of Biochemistry and Molecular Pharmacology and Director of the Institute of Systems Genetics at New York University, developed an undergraduate-level intensive laboratory course to teach practical aspects of molecular biology, synthetic biology, and bioinformatics, allowing students to perform extensive research in a class setting.

Build-a-Genome (BAG) course 

Boeke studied transposable elements in yeast and mammalian cells. Along the way, he decided to synthesize transposon DNA from scratch. “I was impressed with the power of being able to do that, which led me to synthesize first a synthetic chromosome arm and eventually the entire yeast genome with people around the world,” he describes. Using this first synthetic eukaryotic genome project, Boeke developed a unique laboratory component for his class that allowed students to contribute to this mammoth research endeavor.

“We built the genome from scratch, starting with oligonucleotides to entire genomes worth of synthetic chromosomes, piece by piece. In the early phases, we involved a lot of undergraduate students,” he explains. For Boeke, the course had two essential components. “One was to use the manpower needed to build such an enormous genome. The other was that it’s a fantastic way to teach molecular biology and genetics to undergraduate students, for whom it was new. They were doing original research as part of a course, learning about how to do a PCR reaction,” he shares. Because students were synthesizing genome fragments that were never created before, they faced several setbacks and performed extensive troubleshooting. This integral component of the course provided an authentic research experience to students.

Eventually, the course evolved as the technologies advanced. In the early years, students would generate 750 base pairs (bp) of synthetic fragments using PCR reactions on overlapping oligos. They would run gels to get clean bands and regularly present their observations in lab meetings. However, as the cost of synthesizing synthetic DNA fragments rapidly decreased, the course shifted from fundamental molecular biology in E. coli to yeast genetics. “The students started assembling medium-sized DNA pieces into bigger pieces using homologous recombination in yeast. After successfully running the course for 20 years and using work from undergraduate students, they are now helping combine sixteen fully man-made synthetic chromosomes and put them into a single strain,” says Boeke.

“Running the course wasn’t always easy,” describes Patrick Cai, Professor of Synthetic Genomics at the Manchester Institute of Biotechnology and former course instructor. “Boeke was running the course on a very limited budget, so we did a lot of work ourselves. One night, he drove his pickup truck and two of us moved all the chairs across the campus to a new course location. He was that dedicated and serious about the course,” says Cai.

With Boeke’s steadfast commitment and exceptional planning, the course eventually culminated in a global research and teaching consortium. Researchers from across the globe came to Boeke’s laboratory and learned teaching modules to build their parallel courses. “For example, Yingjin Yuan, Professor of Biochemical Engineering at Tianjin University, came to us and we helped him set up this course in China. He and colleagues focused on turning the course into a production machine and developed a landmark project by finishing one whole synthetic yeast chromosome in just a year,” says Boeke.

Teaching how to teach

Boeke involved his graduate students and postdoctoral researchers in teaching the course. According to Lisa Scheifele, Associate Professor in the Department of Biology at Loyola University Maryland, “The number of postdoctoral fellows and graduate students who have been empowered to learn the art of teaching, mentoring students, and developing course structure and content is notable and impressive.” She adds, “Boeke has been incredibly supportive of trainees who wanted to include a significant teaching aspect in their future careers. The Build-a-Genome course was my first teaching experience that ‘lit the fire’ for a future career where I’ve been able to blend teaching and cutting-edge research as we have done in Build-a-Genome.” Plus, the fact that this course inspired several of Boeke’s trainees in pivoting to a teaching career is something he’s quite proud of.

Harnessing the power of designer yeast

The synthetic yeast genome built through this innovative laboratory course offered a major paradigm shift in genetics and biotechnology, showcasing how to design and assemble synthetic DNA at scale. These synthetic chromosomes further facilitate testing genome fundamentals traditionally difficult to dissect in laboratory yeast strains. “Our knowledge about yeast genetics is largely based on our observation of the natural yeast genomes, which sometimes can be difficult to study. The synthetic yeast genome allows us to engineer the genomes to address societal challenges,” explains Cai. For example, Boeke made a bold choice to remove all the tRNA genes from the synthetic chromosomes and put them all on a new chromosome, allowing researchers to engineer it independently of all the other chromosomes. Now, Cai is testing yeast strains with tRNAs adapted to human codon usage to better express human proteins that can in turn be used in therapeutic applications to increase product yield.

Join us in congratulating Jef Boeke, who received the Elizabeth W. Jones Award for Excellence in Education, on behalf of Build-A-Genome, at The Allied Genetics Conference 2024 in Metro Washington, DC. And congratulations to the Build-a-Genome team whose members include Jessica Dymond of In-Q-Tel; Lisa Z. Scheifele of Loyola University Maryland; Eric Cooper of Hartwick College; Robert Newman of North Carolina Agricultural and Technical State University; Franziska Sandmeier of Colorado State University, Pueblo; Yu (Jeremy) Zhao of NYU Langone Health; Stephanie Lauer of St. Thomas Aquinas College; and Raquel Ordoñez of NYU Langone Health.

2024 GSA Awards Seminar Series

On May 28, at 1:00 p.m. EDT, Jef Boeke, who is receiving this award on behalf of Build-a-Genome, will describe how the course teaches students fundamental principles of genetics and how to perform, interpret, and troubleshoot an experiment when the outcome is unknown. Additionally, he’ll touch on the history of the course and the resultant Network of Build-a-Genome courses, how it has affected students and instructors, and the course’s impact on the overarching International Sc2.0 project. Save the date and register here.

Sejal Davla, PhD, is a neuroscientist, science writer, and data scientist with expertise in research in a variety of life sciences. She has more than a decade of experience studying the brain by using cutting-edge methodologies in microscopy, molecular biology, genetics, and biochemistry, and is a motivated storyteller and science communicator.