Kate Adamala has a vision of the future. In this context, biology would replace chemical manufacturing.
“The ultimate success,” says the synthetic biologist, would be that “all the atoms we move around in our economy are moved with biology.”
Adamala and his colleagues at the University of Minnesota in Minneapolis announced a step toward that future on July 1 when the team unveiled SpudCells, synthetic cells which can replicate their DNA and divide several times.
Some people have hailed SpudCells as the first synthetic life. Adamala is not one of them. SpudCells “obviously don’t live,” she says. “They are cells but they are not alive.”
SpudCells are little more than bubbles of fatty membranes containing DNA and proteins borrowed from various viruses and bacteria. Ultimately, these synthetic cells may be able to produce chemicals, fuels and drugs such as antibiotics, Adamala says. SpudCells can’t do that yet.
Unlike natural living cells, SpudCells are not self-sufficient. To function, they need researchers to feed them bubbles filled with protein-producing machines and raw materials. Researchers also need to chemically induce the SpudCells to “grow” – to fuse with the feeding bubbles and take on cargo – and to divide.
Fusion and division depend on proteins encoded by the cells’ DNA. It’s innovation that sets SpudCells apart from previous attempts to build cells from scratch, says physicist Tom Robinson of the University of Edinburgh in Scotland. Robinson and others produced membranes that can divide like cellswhile other groups have successfully replicated DNA in artificial cells. But linking the two in a way that DNA controls growth and division has never been done before, he says.
Robinson was not involved in this work, but he joined Biotic, an international nonprofit research coalition led by Adamala and three other scientists. “We’ve pushed this technology as far as a single lab can push it alone,” says Adamala. “We need collaborators to add their expertise. »
Biotic, short for Biology is Open Technology Inspiring Civilization, Inc., will coordinate and fund research aimed at transforming SpudCells into independent cells. It will also standardize protocols and methods used to construct synthetic cells.
“We’re pretty far from a functional synthetic cell,” Robinson says, “but we’re well on our way.”
build protein. Assembling these massive structures costs natural cells enormous amounts of energy, says biophysicist Jamie Williamson of the Scripps Research Institute in La Jolla, California. “In bacteria, about a third of ribosomes actually make parts of [other] ribosomes so that cells can divide,” says Williamson. “It’s a big challenge for a protocell to take on this task.”No one has yet managed to create functional ribosomes from scratch. “It requires – all biology requires – such precision,” says developmental biologist Douglas Blackiston of Tufts University in Medford, Massachusetts. “Mistakes become catastrophic very, very quickly.”
Natural cells have many levels of quality control to correct errors that synthetic systems typically lack. If bioengineers ever succeed in building ribosomes, they will also need to build cellular maintenance teams to keep the machines running smoothly, Blackiston says.
The systems of natural cells are so intertwined that humans who attempt to build synthetic cells have difficulty imitating them. “It seems like the more we try to micromanage them, the more successful we are,” Blackiston says.
A cleaning system to recognize and degrade spent or damaged proteins is on Adamala’s list of must-have parts for future iterations of SpudCells. The same goes for the cytoskeleton, an internal scaffolding that helps cells organize their interior, maintain their shape, move cargo and splitting DNA during division. It’s important for legacy.
The SpudCells genome is divided into seven DNA circles. For cells to function properly, they must inherit at least one copy of each circle. Without a cytoskeleton to guide division, only about 30% of SpudCells inherited the complete genome in seven parts after five generations, Adamala and colleagues reported in their manuscript, published on bioRxiv.org the day after the announcement and which has not yet been peer-reviewed.
Their insides are also a mess. When the SpudCells merge with the feeder bubbles, “everything comes in and mixes at will. We need to solve this problem,” Adamala says. “We can’t have this gumbo.”
She has big plans for SpudCells – named to evoke the Pioneering Sputnik satellite — over the next 18 months, starting with organizing a meeting of scientists interested in joining Biotic. The coalition is just one of many groups scattered across the United States, United Kingdom, Europe, Asia and elsewhere trying to build synthetic cells from scratch. Many of these efforts use the same tools that helped create SpudCells.
“The work is not finished,” says Adamala. “This isn’t an announcement that feels like a mic drop. ‘We did it. We’re going home.’ It’s an announcement that shows we’ve shown what’s possible.
