SYNTHETIC cells made by combining components of Mycoplasma bacteria with a chemically synthesised genome can grow and divide into cells of uniform shape and size, just like most natural bacterial cells.

In 2016, researchers led by Craig Venter at the J. Craig Venter Institute in San Diego, California, announced that they had created synthetic “minimal” cells. The genome in each cell contained just 473 key genes thought to be essential for life.

The cells were named JCVI-syn3.0 after the institute and they were able to grow and divide on agar to produce clusters of cells called colonies.

But on closer inspection of the dividing cells at the time, Venter and his colleagues noticed that they weren’t splitting uniformly and evenly to produce identical daughter cells as most natural bacteria do. Instead, they were producing daughter cells of bizarre shapes and sizes.

“[The creators of JCVI-syn3.0] had thrown out all the parts of the genome that they thought were not essential for growth,” says Elizabeth Strychalski at the US National Institute of Standards and Technology. But their definition of what was necessary for growth turned out to be what was needed to make beautiful colonies growing on an agar plate, she says, rather than what was needed to produce cells that divide in a uniform and lifelike way.

By reintroducing various genes into these synthetic bacterial cells and then monitoring how the additions affected cell growth under a microscope, Strychalski and her team were able to pinpoint seven additional genes required to make the cells divide uniformly.

When the researchers added these seven genes to JCVI-syn3.0 to produce a new synthetic cell, they found that this was enough to restore normal, uniform cell division and growth.

Strychalski and her colleagues found that while two of the seven genes were already known to be involved in cell division, five were previously without a known function. “It was surprising,” she says.

“Those five genes were outside the scope of what we had known about,” says James Pelletier at the Massachusetts Institute of Technology, a co-author of the study.

“The minimal cell has many genes of unknown function that, although we have no idea what they do, they are necessary for the cell to live – so that’s an exciting area for future research,” he says.

“[This research] is incredibly important for understanding how life works and what genes are needed to operate cells reliably,” says Drew Endy at Stanford University in California.

“Basic research on minimal cells helps us understand the principles of the phenomena of life, and the evolutionary history of life,” says Kate Adamala at the University of Minnesota in Minneapolis. This is because the minimal cell is a good analogue of the last universal common ancestor of all life on Earth.

The new finding also “brings us closer to engineering fully defined, understood and controllable” live cells, she says. “Free of the complexity of natural live systems, synthetic cells are a tool for both basic research and biotechnology.”

“The potential applications are vast, in agriculture, nutrition, biomedicine and environmental remediation,” says Jef Boeke at New York University. “The ability to correct and refine biological code like this is a crucial step to getting us there.”

Journal reference: Cell, DOI: 10.1016/j.cell.2021.03.008