New findings shed light on mechanisms controlling the most basic processes of life.
Five years ago, scientists created a single-celled synthetic organism that, with only 473 genes, was the simplest living cell ever known. However, this bacteria-like organism behaved strangely when growing and dividing, producing cells with wildly different shapes and sizes.
Now, scientists have identified seven genes that can be added to tame the cells’ unruly nature, causing them to neatly divide into uniform orbs. This achievement, a collaboration between the J. Craig Venter Institute (JCVI), the National Institute of Standards and Technology (NIST) and the Massachusetts Institute of Technology (MIT) Center for Bits and Atoms, is described in the journal Cell.
Identifying these genes is an important step toward engineering synthetic cells that do useful things. Such cells could act as small factories that produce drugs, foods and fuels; detect disease and produce drugs to treat it while living inside the body; and function as tiny computers.
But to design and build a cell that does exactly what you want it to do, it helps to have a list of essential parts and know-how they fit together.
“We want to understand the fundamental design rules of life,” said Elizabeth Strychalski, a co-author on the study and leader of NIST’s Cellular Engineering Group. “If this cell can help us to discover and understand those rules, then we’re off to the races.”
Scientists at JCVI constructed the first cell with a synthetic genome in 2010. They didn’t build that cell completely from scratch. Instead, they started with cells from a very simple type of bacteria called a mycoplasma. They destroyed the DNA in those cells and replaced it with DNA that was designed on a computer and synthesized in a lab. This was the first organism in the history of life on Earth to have an entirely synthetic genome. They called it JCVI-syn1.0.
Since then, scientists have been working to strip that organism down to its minimum genetic components. The super-simple cell they created five years ago, dubbed JCVI-syn3.0, was perhaps too minimalist. The researchers have now added 19 genes back to this cell, including the seven needed for normal cell division, to create the new variant, JCVI-syn3A. This variant has fewer than 500 genes. To put that number in perspective, the E. coli bacteria that live in your gut have about 4,000 genes. A human cell has around 30,000.
“We want to understand the fundamental design rules of life. If this cell can help us to discover and understand those rules, then we’re off to the races.” — Elizabeth Strychalski, a co-author on the study and leader of NIST’s Cellular Engineering Group
Identifying those seven additional genes took years of painstaking effort by JCVI’s synthetic biology group, led by co-author John Glass. Co-lead author and JCVI scientist Lijie Sun constructed dozens of variant strains by systematically adding and removing genes. She and the other researchers would then observe how those genetic changes affected cell growth and division.
NIST’s role was to measure the resulting changes under a microscope. This was a challenge because the cells had to be alive for observation. Using powerful microscopes to observe dead cells is relatively easy. Imaging live cells is much harder.
Holding these cells in place under a microscope was particularly difficult because they are so small and delicate. A hundred or more would fit inside a single E. coli bacterium. Tiny forces can tear them apart.
To solve this problem, Strychalski and MIT co-authors James Pelletier, Andreas Mershin and Neil Gershenfeld designed a microfluidic chemostat — a sort of mini-aquarium — where the cells could be kept fed and happy under a light microscope. The result was stop-motion video that showed the synthetic cells growing and dividing.
This video shows JCVI-syn3.0 cells — the ones created five years ago — dividing into different shapes and sizes. Some of the cells form filaments. Others appear to not fully separate and line up like beads on a string. Despite the variety, all these cells are genetically identical.
This video shows the new JCVI-Syn3A cells dividing into cells of more uniform shape and size.
These videos and others like them allowed the researchers to observe how their genetic manipulations affected the cell growth and division. If removing a gene disrupted the normal process, they’d put it back and try another.
“Our goal is to know the function of every gene so we can develop a complete model of how a cell works,” Pelletier said.
But that goal has not been reached yet. Of the seven genes added to this organism for normal cell division, scientists know what only two of them do. The roles that the other five play in cell division are not yet known.
“Life is still a black box,” Strychalski said. But with this simplified synthetic cell, scientists are getting a good look at what’s going on inside.
Reference: “Genetic requirements for cell division in a genomically minimal cell” by James F. Pelletier, Lijie Sun, Kim S. Wise, Nacyra Assad-Garcia, Bogumil J. Karas, Thomas J. Deerinck, Mark H. Ellisman, Andreas Mershin, Neil Gershenfeld, Ray-Yuan Chuang, John I. Glass and Elizabeth A. Strychalski, 29 March 2021, Cell.
… I hope the God is watching…
If you’re a deist, then you must assume your god has better things to do than pay attention to Homo sapiens. If you’re a theist, then why are you even reading about science?
Interesting, playing to be God…
Science creation is good if it follow ethical and moral rules… I hope that all those creations do not end up outside the lab, growing alone without control… And as everything, what happen if this knowledge ends up in the wrong hands?… this can destroy what we know as life until today (look what one virus has done in one year)… I hope God is watching them…
Misleading title. They tampered with life and did not “forge” it, which implies creating life from scratch.
I hope this does not turn out to be the Frankenstein that eliminates its creators.
The moment in time has arrived again to ask the question. Just because we can, does it mean we should? Solomons time…. nothing new under the sun, what has been done will be done again. Look to our past to learn, look to our future to live!
Oui, c’est plus de la manipulation que de la création de cellules.
Les apprentis-sorciers doivent maitriser leurs limites !
Are we wasting tax-payer’s money to play God? Why? There is good science and there is bad science. Even science proves the existence of God. Good science does not question the doing, nor try to be better than the Creator of all mankind! God is watching! And we praise Him that He is! The time is near!
Just remember, this is all part of your god’s plan…..stop complaining about it people. Mmmkay
“Strychalski and MIT co-authors James Pelletier, Andreas Mershin and Neil Gershenfeld designed a microfluidic chemostat — a sort of mini-aquarium — where the cells could be kept fed and happy under a light microscope.”
The thought of a mini aquarium for cells to be “happy” is absolutely adorable. Now I can’t stop thinking of a scientist looking through a microscope, speaking to a lump of cells like they’re puppies.
Another fake claim.
Just where did they get the “parts” to assemble this little artificial cells? Did they start with chemicals and synthesize all the parts themselves, which would be astounding, or did they just change and shuffle around existing structures, which is old hat….sigh
Unfortunately, they only manipulates what was already in existence. God says start with your own quark’s etc.
Those claiming this is playing God… you’re an idiot. By your logic then, we shouldn’t be performing CPR, giving diabetic people insulin, or really any life saving procedures or medicines. THIS IS HOW WE GOT THOSE THINGS. BY LEARNING THROUGH SCIENCE. Do us all a favor and don’t breed if you’re honestly that dumb. The article literally said it’s going to help them SAVE people etc.
I’ve always found it ironic how bible-thumpers are willing to embrace concepts like miracles, resurrection, the virgin birth, etc without question yet at the same time they’ll angrily deny ‘miraculous’ tools for curing the sick (stem cells, gene therapy), push back on research for nanomachines that could one day potentially re-animate a deceased loved one and argue against any kind of artificial insemination (arguably the closest thing there is to a virgin birth, especially for women who can’t conceive the normal way). Talk about the ultimate contradiction. Why would an all-powerful, all-knowing creator make us in His image, only to deny us any advancement beyond being stupid, primitive, fearful creatures? That makes zero sense, even in the context of being a religious nutjob like the ones I’m reading here.
I am nowhere near the expertise level of these scientists. But I am a generational Southern Baptist. Continue to seek the origins of life. Carry on…