For the first time, scientists have discovered what makes the cell’s tiny protein-making machines run — and have built their own molecular gadget. They created a ribosome, the factory for proteins within the cell, inside a living cell, where it worked just like its natural counterpart, according to a report in the journal Nature. This finding means it may soon be possible to harness these little machines to produce more complex proteins, perhaps — one day — for use in medicine.
But the scientists did something even more remarkable: they changed the structure of the protein factories themselves. In nature, ribosomes are split in halves, which float around separately inside the cell until it’s time to produce a protein. To keep the lab-made ribosome from linking up with the naturally occurring ones — which would kill the cell — the scientists tethered the two halves together.
Keys to the protein-making factory
This change in ribosome structure may have accounted for the attempt’s success — scientists have tried to produce them in the past. They’re crucial structures in the cell; if DNA is a blueprint, the ribosomes are the carpenters. Making one from scratch might give researchers the ability to make any number of proteins easily, and in large quantities. But until now, no one has been able to make a whole ribosome within a living cell.
"A lot of people consider the ribosome to be the chef of translation and so one of the things we’re curious to know now is if you have the ability to make specialized chefs, chefs that make different types of cuisines," says Michael Jewett, synthetic biologist at Northwestern University and a co-author of the study. These ribosomes could be tailored to only make a certain type of molecule, one that a ribosome has never made before — or one that can be used to mass produce a new drug.
This "sets the stage for the production of entirely new classes of exotic [molecules]."
"Overall, the authors have surmounted a major barrier in constructing fully synthetic and customizable ribosomes," and in doing so, "they've laid the foundation for dramatic alterations of the ribosome not previously seen," says Karissa Sanbonmatsu, a ribosome researcher at Los Alamos National Laboratory who didn’t work on the study. Farren Isaacs, a cellular biologist at Yale University, agrees. The study is "a key advance," that "sets the stage for the production of entirely new classes of exotic [molecules]."
Despite this high praise, the final design remains flawed. Cells that only have the artificial ribosome, called Ribo-T, grow two times slower than cells with normal ribosomes, says Alexander Mankin, a molecular biologist at the University of Illinois at Chicago and a co-author of the study. "Our tethered ribosome is good, but not as good as ‘normal’ ribosome" — at least "not yet." After all, normal ribosomes are the product of several billion years of evolution, "and our Ribo-T is only one year old!" Mankin says.
"Our Ribo-T is only one year old!"
But the point of engineering a protein factory isn’t to improve the naturally occurring version, anyway. If Ribo-T falls short when making regular cellular proteins, but can still be repurposed to make a specific therapeutic protein, "we would be very happy," Mankin says.
No one seems to know what the next steps are. "How do you imagine producing new types of materials as evolvable, living matter? What does that look like? We don’t know," Jewett says. "I think that’s part of the fun, frankly — we don’t know where it is going to lead to."