SpudCell is the first synthetic cell system built from non-living components to complete a full cell cycle Orion Venero, Adamala Lab
The “SpudCell” is being proclaimed by its creators as a major advance in synthetic biology. Some of this hype is justified – yes, it’s a cell, but perhaps not quite what one could call a living cell. It has 36 genes that allow it to copy DNA and replicate in a primitive way, but it needs a lot of outside help and fails after five or so divisions. That is, however, much more than any other team has achieved, so it is arguably the greatest feat of bioengineering to date.
Created by at the University of Missouri and her colleagues, the team is now making the SpudCell project open-source so it can be developed further and even made capable of dividing indefinitely. Here’s what you need to know:
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What is the SpudCell?
It’s a step towards creating a minimal lifeform whose functions are fully understood. Previous attempts involved deleting genes from bacterial cells whose genomes are small to start with. For instance, in 2016 a bacterium with 901 genes was stripped down so it had just 493 genes. Adamala’s team did things the other way round, starting with just 36 genes. These mostly come from E. coli bacteria but there are also some from phage viruses that infect bacteria and one for a fluorescent protein from jellyfish to help make the cells visible.
So, is it a lifeform?
No. It can do some of the things that living cells do, such as replicating its genes and dividing, but it doesn’t do them well, and it needs a lot of outside help just to do them badly. For instance, the researchers have demonstrated evolution in the sense that when they introduced a beneficial mutation, those cells did better. But the mutation had to be introduced deliberately rather than occurring spontaneously. “I think I would be satisfied with calling it living if it’s replicating indefinitely and if it’s capable of Darwinian evolution,” says Adamala.
Can we really call it a synthetic cell, then?
That depends on how you define things. It is a synthetic cell in the sense that it’s been put together in a lab and does some of the things a cell does. But it’s been put together using parts of existing cells – mainly those 36 genes – rather than being created entirely from scratch. It could be thought of as an extremely stripped down E. coli with a few additions from other viruses, bacteria and jellyfish.
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How was it assembled?
The researchers engineered the 36 genes into seven circular pieces of DNA. They made lots of copies of them and put them into a solution containing all the other things the cells need, like the building blocks of DNA and proteins, and fatty molecules that spontaneously form cell-like bubbles. Some of these bubbles ended up with all seven parts of the genome.
The cells are then kept alive by two of the genes coding for proteins that form pores in the membrane, allowing some small molecules to enter. Larger molecules are supplied in the form of small bubbles that fuse with the cells. So the cell is supplied fed with all the building blocks of life, because it can’t make any itself.
How do the cells divide?
The team added large proteins to the solution that bind to one of the protein pores that protrude from the membrane. These jostle for space and cause the membrane to bend, says Adamala, which can result in part of the SpudCell budding off and forming a separate bubble of its own. It’s not an equal division into two parts, and the resulting cells have a random selection of the circular bits of DNA, so many lack the full sets of genes.
Why not just put all the genes on one piece of DNA?
This would be better to ensure daughter cells get all of the genes but it’s very hard to work with such large pieces of DNA, Adamala says. “Once we have a genome we’re happy with, it definitely has to go on a single large [piece].”
SpudCell, with it’s red membrane stained with a lipid dye Orion Venero, Adamala Lab
Why do the cells stop doing anything after about five rounds of division?
The team doesn’t know for sure, but the cells are not capable of making their own protein-making factories, or ribosomes. They have to be supplied with them. “We’re speculating that it is because of the failure of the ribosomes [that the cells stop dividing],” Adamala says. So once the cells can make their own ribosomes, they may be able to keep dividing indefinitely. “I think it is achievable very soon.”
This is all very impressive, but why create SpudCell in the first place?
“We want to be able to make all petrochemicals with living biology, so we can basically move away from oil for all the climate and societal benefits,” Adamala says. Virtually all of the chemicals we depend on, from plastics to pesticides, are derived from oil and gas. Many of these chemicals are toxic, she says, and would kill normal cells that made them. But synthetic cells could be designed to tolerate them.
Could it ever be dangerous?
No. It’s a bed-ridden Frankenstein’s monster that has to be spoon-fed. There’s no danger of it running amok. And even if it really can be brought fully to life, it’s unlikely to be able to survive outside a lab or factory. Existing bacteria are a far greater threat.
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