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Mimicking living cells: Synthesizing ribosomes

engineer new or novel life forms and biocatalytic ensembles for useful purposes.

The findings of the four-year research project were published June 25 in the journal Molecular Systems Biology.

Comprising 57 parts -- three strands of ribonucleic acid (RNA) and 54 proteins -- ribosomes carry out the translation of messenger RNA into proteins, a core process of the cell. The thousands of proteins per cell, in turn, carry out a vast array of functions, from digestion to the creation of antibodies. Cells require ribosomes to live.

Jewett likens a ribosome to a chef. The ribosome takes the recipe, encoded in DNA, and makes the meal, or a protein. "We want to make brand new chefs, or ribosomes," Jewett said. "Then we can alter ribosomes to do new things for us."

"The ability to make ribosomes in vitro in a process that mimics the way biology does it opens new avenues for the study of ribosome synthesis and assembly, enabling us to better understand and possibly control the translation process," he said. "Our technology also may enable us in the future to rapidly engineer modified ribosomes with new behaviors and functions, a potentially significant advance for the synthetic biology field."

The synthesis process developed by Jewett and Church -- termed "integrated synthesis, assembly and translation" (iSAT) technology -- mimics nature by enabling ribosome synthesis, assembly and function in a single reaction and in the same compartment.

Working with E. coli cells, the researchers combined natural ribosomal proteins with synthetically made ribosomal RNA, which self-assembled in vitro to create semi-synthetic, functional ribosomes.

They confirmed the ribosomes were active by assessing their ability to carry out translation of luciferase, the protein responsible for allowing a firefly to glow. The researchers then showed the ability of iSAT to make a modified ribosome with a point mutation that mediates

Contact: Megan Fellman
Northwestern University

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