In The Field

Minimal life: Engineering the simplest life

On the first day’s afternoon at the NSF workshop on “minimal life”, discussants took an engineering approach to understanding the simplest forms of life. Here, engineers are sort of the “cheaters” of the group — unlike the other scientists, they get to understand the minimum required for life by looking at things that are simpler than what naturally occur in nature.

Clyde Hutchison of the J Craig Venter Institute said the ultimate goal of his work was “a complete description of biological systems in terms of the laws of chemistry and physics.” While physicists have the hydrogen atom as their simple model organism, biologists must use minimal cells. He’s not talking about chunky, complicated yeast — his cell of choice is Mycoplasma genitalium, the smallest cell that can be grown independently in the labroatory, and its 580 kb genome, the smallest known genome of any bacterium capable of independent life, he says. And even that’s not little enough for his fancy: he wants to see how much of it he can trim away and still have the tiny thing function.

“Are there cells that can live in the lab that are significantly simpler than cells that exist in nature?” he asks.


His basic strategy is to first synthesize and assemble the entire chromosome, then start hacking away and sticking the trimmed down versions in Mycoplasma cytoplasms to see if they still grow. So far he’s working on getting the recipient cells to accept the synthetic genome — a tricky feat because the genome is synthesized in yeast, and it’s difficult to get it out intact. But he’s been able to get the system to work using naked whole genomic DNA as the donor and another bacterial cell as the recipient, “putting us well along the way of making a synthetic cell”.

Tom Knight of MIT, a leader in synthetic biology, was up next, and talked about engineering organisms from the smallest number of simple parts. He spoke of the necessity of standardized parts for engineering, and specifically of the Biobricks project that he helped found.

His strategy seems similar to Hutchison’s — start with a simple organism and systematically take stuff out until it breaks. He chose “an organism which absolutely no one cares about”, he said — Mesoplasma florum, commonly found in insect guts. The bacterium has a genome less than 800 kb long and an impressive lack of functionality: It can’t make any of its own amino acids or cofactors, or carry out the citric acid cycle. Basically all it does it make and break down proteins. So far he’s sequenced the genome and is currently developing “genome engineering tools” like custom transposons.

Next came Sheref Mansy of the University of Trento, in Italy, with perhaps the most minimalistic, bottom-up approach. If you want to create the simplest replicating cells, forget proteins and phospholipids (the primary components of our cell membranes). Last year, he was able to create a protocell that replicated its DNA using only four components: fatty acids to make the membrane, and DNA template, primer and activated nucleotides. There are many limitations to his protocell, such as the inability to use support the function of proteins, but it seems pretty exciting to get even these properties from such a barren bag of chemicals.

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