Thursday, September 6, 2012
Students Use New Technology to Sequence Genomes
Reading the instructions encoded within our DNA holds the promise of a better understanding of health, disease and life itself, and presents one of the newest and most exciting challenges for career biologists. Carnegie Mellon’s Department of Biological Sciences is preparing students to meet this challenge. As part of the Howard Hughes Medical Institute-funded Phage Genomics Research course, first-year students are getting hands-on experience in reading the genomes of viruses that infect bacteria, known as bacteriophages (phages for short), using one of the newest and most promising technologies available.
Last year’s class was the first to use Life Technologies’ Ion Personal Genome Machine (PGM). The PGM uses the semiconductor-based Ion Torrent DNA sequencing technology invented by CMU alumnus and entrepreneur Jonathan Rothberg (E’85).“Our goal is to get students doing science as early as possible and to expose them to the latest ideas, latest research and latest technologies. The use of Ion Torrent in the Phage Genomics course is a great example of the kind of excitement that can be generated when these all come together. I predict that giving first year undergraduates this kind of experience will be a transformative event in their college career.” said Nathan Urban, Frederick A. Schwertz Distinguished Professor of Life Sciences and Head of the Department of Biological Sciences.
While the first students to use the PGM are just beginning their sophomore years, they think Urban’s prediction rings true.
“It was awe-inspiring to use such new technology, especially since we were first-years,” said computational biology major Rene Francolini (S ’15). “This is something you could only get at Carnegie Mellon, and that’s what makes this school so unique.”
“It was a great opportunity to be able to do real research in the lab,” added chemistry and physics major Lauren O’Neil (S ’15). “I recently read an article about Ion Torrent and I felt knowledgeable. I realized that cutting-edge research isn’t miles beyond my dreams. I thought if I could do this as a first year, everything else seems possible.”
The Ion Torrent chip also is used in Life Technologies’ Ion Proton Sequencer, which has been heralded for its ability to sequence the 3 billion base pairs in a person’s DNA in one day for $1,000. The smaller PGM is ideal for the sequencing the DNA of less complex organisms like phages or bacteria, which contain up to a few million base pairs, or for sequencing selected regions of more complex genomes.
“As first year students, they were totally inexperienced. We didn’t know if it was possible for them to sequence the genome of a phage,” said associate professor of Biological Sciences Javier Lopez. “But, with the PGM we had a fantastic result. Every student was able to sequence, assemble and annotate a genome.”
In the Phage Genomics Research course, taught by Lopez, Associate Professor of Biological Sciences Jonathan Jarvik and Assistant Teaching Professor Maggie Braun, the students isolate a bacteriophage from soil samples taken from around the country. They then characterize their phage’s structure using electron microscopy and clone its DNA. The DNA is digested into manageable fragments about 100 to 200 base pairs in length. The fragments are incorporated into tiny microscopic beads and a solution containing the beads is loaded on to the Ion Torrent semiconductor chip. Each bead settles into one of the more than one million microscopic wells etched into the chip. When the chip is fed into the PGM, the DNA sequence is copied by enzymes. As this happens, the PGM can identify each base pair in the sequence by detecting a subtle change in pH. The data are fed into a computer and assembled into a sequenced genome that the students can read. They compare the genomes of their phages with previously cataloged phages to look for differences that may play a role in their phage’s function.
Before the PGM, sequencing the genome of the phages was difficult, time-consuming and expensive. Each year, the class could select only one phage to sequence, and the sequencing would be done by an off-site service. But even with these limitations the students were able make important discoveries about how phages behaved and evolved – some of their findings have been published in journals and presented at scientific meetings. Now with the PGM, each of the 16 students can sequence the genetic material of their own phage.
“Now that we can read the genomes of more phages, we expect to find many more interesting and unexpected things,” said Lopez.
By: Jocelyn Duffy, firstname.lastname@example.org, 412-268-9982