A New Model Organism Could Double the Pace of Biology
Theodor Escherich was studying baby poop when he made the discovery that would set the course for modern biology. In Germany at the time, babies were dying of diarrhea. When Escherich peered through his microscope at bacteria taken from the babies, he saw rod-shaped bacteria that would come to bear his name: Escherichia coli.
That was 1857. Fast forward 150 years and E. coli is a workhorse of modern biology. Early microbiologists discovered that E. coli grew well in the lab, in broths or in plates of agar with even minimal nutrition. And when the genetics revolution came along, geneticists deciphered its small genome—one one-thousandth the size of a human’s—and figured out how to manipulate its DNA. The common lab strains are too tame to give you diarrhea now. Studies using E. coli, from probing the basics of DNA to engineering strains that make antibiotics, would fill shelf upon shelf.
But a new paper from the lab of Harvard genetics pioneer George Church’s offers up an intriguing alternative: The bacterium Vibrio natriegens grows even faster than E. coli. It could cut in half the amount of time geneticists spend on routine experiments. The even more intriguing outcome, says Henry Lee, a postdoctoral researcher in Church’s lab who is working with V. natriegens, is this that study charts a course for taming microbes, taking them from the wild into the lab in months rather than decades. A preprint of the paper, which has not been peer-reviewed, appeared on the bioRxiv repository this month.
V. natriegens comes from the mud of a salt marsh, and it has a reputation as a speedy grower. It doubles in number every 10 minutes—compared to 20 minutes for E. coli in ideal growth conditions. But V. natriegens needs to do more than grow fast to be useful, and that’s where E. coli has the incumbent advantage. “Over the course of a hundred years of intense study, we have a huge amount of information about the organism, more than any other on Earth,” says Adam Arkin, a biologist at the University of California, Berkeley, who was not involved in the study.
For the past four years, Lee has been trying to catch V. natriegens up. He’s scoured the old E. coli literature to see how early microbiologists turned it into a malleable lab organism. “It’s been a very fun, really humbling process,” says Lee. In the beginning, “you don’t know how to make heads or tails of anything.”
For example, Lee had to figure out how to insert foreign genes into V. natriegens, a process that is trivial with E. coli. First, he needed to make a circular piece of DNA, called a plasmid, that could sneak into V. natriegens cells. And he needed to somehow quickly differentiate between V. natriegens colonies that have taken up the plasmid and those that do not. With E. coli, you buy can off-the-shelf plasmid constructs that turn the bacteria one color when the transformation is successful and another when it is not. Lee had to construct the whole plasmid himself.
He eventually got the transformation working, along with two other genetic manipulation techniques: interrupting existing genes in V. natriegens and inactivating them with Crispr. “He proved he has a toehold on most of the genetics, which give us all faith he’ll get it working pretty well,” says Arkin.
Arkin says he’s skeptical V. natriegens itself could supplant E. coli in labs, but interest in working out genetics tools for all kinds of obscure bacteria is only going to continue to grow. E. coli is very good at growing in human bodies. But what if synthetic biologists want to engineer bacteria that can sequester carbon in oceans or ones that keep plants healthy during a drought? Well then you want bacteria that, after millions of years of evolution, are already very good at living in oceans or living soil.
Who knows where the next world-changing microbes will come from. But if scientists have a road map for quickly working out their genetics, it won’t take a century to put them to use next time.
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