Scientists develop synthetic cell that grows and divides uniformly

Scientists have identified seven genes that can be added to a single-celled synthetic organism, causing them to neatly divide into uniform orbs. The study was conducted by researchers from the J Craig Venter Institute (JCVI), the National Institute of Standards and Technology (NIST) and MIT, all US. 

According to the researchers, identifying these genes is an important step towards engineering synthetic cells that 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.

“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. 

Scientists at JCVI constructed the first cell with a synthetic genome in 2010. To build this cell, 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 synthesised in a lab. The cell was called JCVI-syn1.0.

Since then, scientists have been working to strip the organism down to its minimum genetic components. The super-simple cell they created five years ago, dubbed JCVI-syn3.0, was minimal. 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. 

A photo showing cells of the synthetic organism JCVI-syn3A growing and dividing under a light microscope, from a research collaboration between the JCVI, the NIST and MIT’s Center for Bits and Atoms. The scale bar represents 50 micrometers [credit: E Strychalski, NIST and J Pelletier, MIT].

Identifying those seven additional genes took years. The team constructed dozens of variant strains by systematically adding and removing genes. The researchers would then observe how those genetic changes affected cell growth and division, eventually identifying the right ones. 

The team say that holding these cells in place under a microscope to observe them was particularly difficult because they are so small and delicate. To solve this problem, the researchers designed a microfluidic chemostat – a sort of mini-aquarium – where the cells could be kept fed under a light microscope. The result was stop-motion video that showed the synthetic cells growing and dividing.

One video showed JCVI-syn3.0 cells dividing into different shapes and sizes. Some of the cells formed filaments. Others appeared to not fully separate and line up like beads on a string. Despite the variety, all the cells in that video were genetically identical. Another video showed 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 would 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,” said co-author James Pelletier from MIT. 

The results were published in Cell.