Genetically Engineered Machines? They’re Already Here
At UCLA’s Molecular Biology Institute, we met with synthetic-biology students who work with DNA’s four nucleotide bases just as computer programmers manipulate code.
By S.C. Stuart
As soon as DNA was sequenced, it was just a matter of time before scientists started rearranging the genetic code to build synthetic lifeforms. These genetically engineered machines (GEMs) can become anything from cells transformed into biofuel to synthetic drugs. In this emerging field, synthetic biologists work with DNA’s four nucleotide bases just as computer programmers manipulate code.
PCMag visited UCLA’s Molecular Biology Institute to interview four early-career scientists who are engaged in molecular cloning experiments and to meet their newly created glowing bacterial colonies.
In the lab, Grace Bower, Alan Chen, Winnie Liu, and Timothy Yu were surrounded by traditional instruments, such as glass test tubes and adjustable gas Bunsen burners as well as the latest high-end life-sciences equipment and monitors charting progress. On the shelves above were bottles full of the food their bacteria samples live on (Difco LB Broth, Dextrose Anhydrous, and Bacto Yeast, in case you were curious).
In October, the group will travel to Boston alongside 6,000 other students from around the world for iGEM 2018, where they will present joint research.
“Our project is working with Vibrio natriegens (V. nat), a marine bacterium, which is isolated from salt marsh mud, as a new molecular chassis. But further genetic tools must be developed before its full potential can be reached,” said Bower, a second-year Microbiology, Immunology, and Molecular Genetics major.
“As the biotech field moves from the lab into industry, we need more options than just E. coli, which dominates as the primary microbial model simply because it is the most researched and convenient, and we know how it works,” she explained.
“But there are trade-offs in terms of how fast E. coli grows or how economically it utilizes various biosynthesis pathways such as insulin production or PHB bioplastic generation, incubation temperature, issues with particular substrates, and so on. So industry is asking us scientists to find new source materials quick enough to keep up with demand and lower consumer cost,” added Liu, a second-year Molecular, Cellular, and Developmental Biology major minoring in Biomedical Research.
At the moment, E. coli takes up to two days to grow, but V. nat takes half that time for increased protein expression. So it provides a more efficient and better view to analyze in the lab.
“V. nat grows really fast,” Chen, a fourth-year Neuroscience major, pointed out. “Which makes it very attractive for industry purposes. It has a lot of value as a new chassis organism. We’re not trying to replace E. coli but add to the range of bacterial strains and species that we can use.
“There is an incredibly diverse set of biosynthesis pathways that one can optimize in E. coli then transfer to V. nat for mass production of pharmaceuticals to environmentally friendly materials, and much more.”
“There are many ways to manipulate genetic elements and it’s exciting that some of the graduate students we collaborate with have developed a novel method of quantifying the gene expression of thousands of different DNA sequences in a single assay,” said Yu, a second-year Bioengineering major. “We’re harnessing that method to create a toolbox of characterized promoters in V. nat, so if someone would like to use it as a host organism to perform a difficult process in metabolic engineering such as fine-tuning a metabolic pathway to produce insulin or synthesizing a drug, they can do so at incredibly optimal efficiencies.”
The team doesn’t store the original samples of bacteria, just elements of its modified DNA genetic form.
“We record what we call a dynamic range, or a list of the promoters, in that ‘This DNA sequence is really strong, this one isn’t.’ So when someone else comes along to build a plasmid [a genetic structure in a cell that can replicate independently of the chromosomes, typically a small circular DNA strand in the cytoplasm of a bacterium], they can go to our characterized library of gene sequences, find the optimum promoter for their experiment, and put that in,” Bower said.
“When we get a plasmid we really like,” added Chen, “we can store it at minus 80 degrees for a very long time in a glycerol stock. Then it’s very stable, so if you want to access it later, it’s still viable.”
In fact, there’s a thriving “bacteria exchange program” between labs, where genetically modified components are stored in secure environments.
“We would like to publish peer-reviewed papers online,” added Liu, “so other scientists can use our work. But what’s cool about competing in iGEM is that other students get early stage exposure to a range of inspirational ideas, and might expand on those while they’re still in school as part of their graduate studies at a later date.”
UCLA created its first iGEM team back in 2012, but it didn’t start competing at the national level until 2015 with the Silk Genetics project, which won a gold medal. The project was an important breakthrough because the genetically engineered silk could be used in medical scenarios, such as sutures and implants, because it elicits a low immune response and is biodegradable.
Chen is the only member of the current iGEM team to have competed before at a national level and was part of a prior award-winning team.
“We took a project called Protein Cages to iGEM in 2016,” said Chen. “and won four gold medals, in several categories, for our work on self-disassembling protein cages, which could be used for targeted drug delivery and would then dismantle themselves inside the body once they reached a blood clot.”
These are no mere student projects. UCLA’s iGEM has already attracted industry support, including financing from IDT (Integrated DNA Technologies), a significant player in CRISPR gene editing. The iGEM team is expanding the frontiers of scientific knowledge, despite their biological youth.
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Originally published at www.pcmag.com.
