Students, Henry Ma and Abena Apaw, on how they go about building a synthetic yeast genome
Henry Ma, a JHU junior,
majoring in biomedical
engineering and public health
A few years ago, Hopkins researchers began synthesizing the genome of Saccharomyces cerevisiae, aka Baker’s yeast, a popular model organism in biology. This yeast genome comprises 12 million nucleotides, or genetic letters, strung together in a particular order. To complete this task, the scientists began the “Build-a-Genome” course, offered at the Hopkins Homewood campus each semester. Henry Ma, a Hopkins junior majoring in biomedical engineering and public health studies, and Abena Apaw, a junior at Baltimore’s Polytechnic High School, are two of the students taking the popular course this semester.
What is the format of the Build-a-Genome?
MA: We began with a month-long boot camp to learn the molecular biology techniques. After that, we come into the lab on our own time to work on our assigned portion of the genome.
Dr. Boeke, one of the course instructors, has created artificial subdivisions of the genome called building blocks. Each building block is 750 base pairs long. Each student is assigned 15 to 19 building blocks to produce over the course of the semester.
Abena Apaw, a junior at
Baltimore's Polytechnic High
So what do you physically do?
MA: There is a software program that breaks down each building block into a sequence of oligonucleotides. An oligonucleotide is a short piece of synthetic single-stranded DNA, about 70 base pairs long, that can be purchased ready-made from a biotech company.
We receive the oligonucleotides in 96-well laboratory plates. Each well contains a different oligonucleotide. Then we begin to put the pieces together in the right order. To do this, we use the fact that each nucleotide has a chemical partner; adenine goes with thymine, and cytosine goes with guanine. The DNA helix is made up of two strands of complementary nucleotides. To begin to make a building block, we take two oligonucleotides that complement each other at portions of their sequence, and mix them with an enzyme to help them bind together. Then we find another oligonucleotide and continue to build the sequence.
It’s sort of like Legos. One Lego—or oligonucleotide—will overlap another, which will overlap another until you have a long line of connected Legos that look something like steps. Then we add an enzyme called Taq polymerase that makes a lot more of the synthetic DNA.
What is the most important thing you’ve learned in the course?
APAW: I think I’ve learned a lot about being very thorough, meticulous and cautious about what I’m doing—like making sure that when I’m pipetting, I pipette exactly the right [volume of fluid].
I’ve also learned patience. In fact, some of the building blocks do not work. Instead of redoing them, it’s best to move on to the next stage. And then you can go back and see what you can do to get it to work later.
Is that frustrating?
MA: To me, the most interesting part is when something goes wrong. For instance, a person who works next to me couldn’t get one sequence to work. It just wouldn’t come out to be the right length. The piece of DNA was so fragile. It broke whenever he’d pipette it. The piece turned out to be a telomere end, the tip of the chromosome, which is an especially fragile region.
Would you like to continue doing research? Can you see yourself working on yeast again?
APAW: The course has strengthened my interested in research. I’m mostly interested in human genetics, but I’m open to other areas. I have enjoyed analyzing data and drawing conclusions. The course and synthesis project has also shown me a part of research I do not like, which is the procedure itself; it can be very lengthy.
MA: Previously, I considered dropping research in favor of focusing completely on medicine. I have to say, this course rekindled my interest in research, with respect to the applications of using genetic information to achieve new cures for infectious diseases.