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Organic blobs built in lab may be small step towards synthetic life

Microscopic organic blobs created from scratch could provide clues about how biological cells formed spontaneously on early Earth – and further efforts to generate synthetic life
vesicles
Artificially coloured images of organic blobs created in the lab
Ahanjit Bhattacharya

A new way to make simple organic bubbles could provide fresh clues about how biological cells formed spontaneously on early Earth – and help efforts to generate synthetic life.

Protocells, the ancient ancestors of life today, may have been little more than simple, spherical compartments, enclosed by membranes and containing water and the molecules of life. But how these compartments – or “vesicles” – came about is a mystery.

It is the ultimate “chicken and egg paradox”, says at the University of California, San Diego. The membranes found in modern cells self-assemble in water from molecules called lipids. But in all modern life forms, the proteins that generate lipids only work when embedded in a membrane. In other words, you need a membrane to make a membrane.

Now, Devaraj’s research group has found a way around this constraint. “We basically just [place] some small molecules and DNA into a solution, and out come vesicles that are protein decorated,” says Devaraj.

To perform this trick, the researchers relied on a 20-year-old technology developed to encourage naked DNA, removed from its cell, to still function and generate proteins. The approach involves placing the DNA in a solution with only the basic ingredients needed to translate a genetic code into a protein: 35 or so proteins, a dash of magnesium, a sprinkling of amino acids and other small molecules, plus a few ribosomes – the molecular “machines” inside cells where proteins are synthesised.

Devaraj’s group modified this system to generate one protein needed to create synthetic lipids and a second that can bind to the surface of the vesicles. When they add lipid precursors to the solution, vesicles form spontaneously in solution, and the second protein attaches to the outside of the membrane. This is the first time anyone has used this cell-free, DNA translation system to create a synthetic vesicle from scratch.

“To create them from scratch is really exciting,” says at the University of Oxford, who wasn’t involved in the research. “It’s just building down the complexity even more to simple starting materials.”

That said, the system Devaraj and his colleagues used is still far too complex – and a few billion years too evolved – to mimic the emergence of the very first protocells on early Earth, according to at the University of California, Santa Cruz.

“The first membranes were simply mixtures of fatty acids and fatty alcohols,” says Deamer. “You don’t need phospholipid membranes. That’s an evolutionary step up the complexity scale.”

Devaraj agrees. He says that future versions of vesicles like those he and his colleagues have developed will be more useful for learning about living organisms in the deep past and today, rather than for understanding the origin of cellular life. “How is it that life can organise these molecules in a way that leads to these emergent phenomena like self-reproduction and self-repair and evolution?” he says.

Booth says that any insights from these studies into the origin and organisation of life as we know it may also help in the efforts to generate synthetic life. “If you can make vesicles, then you can think about making them make more vesicles. In which case, you can make things which are more life-like, synthetically,” he says.

Devaraj says this is one of the real goals of his research. “Ultimately, that’s what we’re trying to strive toward. Can you take a known set of parts and assemble them spontaneously in a way that leads to a life-like artificial cell?”

Although this might not help us solve the mystery of how, when or where life appeared, it might help us understand in a little more detail exactly what life needs to emerge and gain complexity. “I think that’s what life has done, right? Across the billions of years,” says Devaraj. “It’s become more and more complicated.”

Journal of the American Chemical Society

Topics: DNA / origins of life