Synthetic Cell With Less Than 500 Genes Successfully Grows And Divides Normally

In a collaborative effort, scientists have created a simple synthetic cell that grows and neatly divides into uniform orbs, replicating some aspects of normal cell division and providing new insights into what genes are fundamental to growth and cell division at a single cellular level.

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“We want to understand the fundamental design rules of life,” said Dr Elizabeth Strychalski, co-author of the study, in a statement. “If this cell can help us to discover and understand those rules, then we’re off to the races.”

Describing their work in the journal Cell, scientists built on previous research from 5 years ago where they created the world's simplest single-celled synthetic organism, called JCVI-syn3.0. It contained only 473 genes – the smallest amount of genes for any known living organism at the time. However, back then, this bacteria-like organism didn't behave like a normal cell would – in fact, it grew and divided into cells of all different shapes and sizes and wasn't really stable.

Now, scientists have been able to get JCVI-syn3.0 cells to grow and divide normally by adding back 19 genes, 7 of which are important for cellular division. After adding the genes back, the newly created cell line JCVI-syn3A behaved much more similar to a normal single-celled organism. Just to put the achievement into context, "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." the press release explained.

A time-lapse video showing cells of the synthetic organism JCVI-syn3A growing and dividing under a light microscope, from a research collaboration between the J. Craig Venter Institute, the National Institute of Standards and Technology, and the Massachusetts Institute of Technology Center for Bits and Atoms. The scale bar represents 50 micrometers.​

To understand which genes were important to put back to restore normal growth and division to the JCVI-syn3.0 cells, the researchers added back one gene at a time to the cell line and then observed the morphological changes under a microscope. If the gene disrupted the normal cell growth and division, they would remove it and try another gene until they found the combination that worked.

Considering this, it was painstaking work by the researchers that uncovered the correct combination of genes required for JCVI-syn3A . Interestingly, the research did uncover that out of the 7 genes related to the cellular division that were added back, only two genes had previously defined functions – the other 5 genes' direct function in the cell division process remains unclear.

Hence the JCVI-syn3A model opens up a new avenue to study single genes in synthetic organisms to uncover their most basic properties.

“Our goal is to know the function of every gene so we can develop a complete model of how a cell works,” co-author of the study, James Pelletier concluded on their research.

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