Mimicking living cells: Synthesizing ribosomes

June 29, 2013

Synthetic biology researchers at Northwestern University, working with partners at Harvard Medical School, have for the first time synthesized ribosomes—cell structures responsible for generating all proteins and enzymes in our bodies—from scratch in a test tube.

Others have previously tried to synthesize from their constituent parts, but the efforts have yielded poorly functional ribosomes under conditions that do not replicate the environment of a living cell. In addition, attempts to combine ribosome synthesis and assembly in a single process have failed for decades.

Michael C. Jewett, a synthetic biologist at Northwestern, George M. Church, a geneticist at Harvard Medical School, and colleagues recently took another approach: they mimicked the natural synthesis of a ribosome, allowing of a cell to help facilitate the man-made construction.

The technology could lead to the discovery of new antibiotics targeting ribosome assembly; an advanced understanding of how ribosomes form and function; and the creation of tailor-made ribosomes to produce new proteins with exotic functions that would be difficult, if not impossible, to make in living organisms.

"We can mimic nature and create ribosomes the way nature has evolved to do it, where all the processes are co-activated at the same time," said Jewett, who led the research along with Church. "Our approach is a one-pot synthesis scheme in which we toss genes encoding ribosomal RNA, natural ribosomal proteins, and additional enzymes of an E. coli cell together in a test tube, and this leads to the construction of a ribosome."

Jewett is an assistant professor of chemical and biological engineering at Northwestern's McCormick School of Engineering and Applied Science.

The in vitro construction of ribosomes, as demonstrated in this study, is of great interest to the field, which seeks to transform the ability to 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 resistance to the antibiotic clindamycin.

The researchers next want to synthesize all 57 ribosome parts, including the 54 proteins.

"I'm really excited about where we are," Jewett said. "This study is an important step along the way to synthesizing a complete ribosome. We will continue to push this work forward."

Jewett and Church, a professor of genetics at Harvard Medical School, are authors of the paper, titled "In Vitro Integration of Ribosomal RNA Synthesis, Ribosome Assembly, and Translation." Other authors are Brian R. Fritz and Laura E. Timmerman, graduate students in chemical and biological engineering at Northwestern.

The work was carried out at both Northwestern University and Harvard Medical School.

Explore further: Scientists identify critical 'quality control' for cell growth

Related Stories

Superbugs may have a soft spot, after all

February 26, 2013

The overuse of antibiotics has created strains of bacteria resistant to medication, making the diseases they cause difficult to treat, or even deadly. But now a research team at the University of Rochester has identified ...

Team discovers how a protein finds its way

April 29, 2013

(Phys.org) —Proteins, the workhorses of the body, can have more than one function, but they often need to be very specific in their action or they create cellular havoc, possibly leading to disease.

Study reveals key step in protein synthesis

June 27, 2013

Scientists at the University of California, Santa Cruz, have trapped the ribosome, a protein-building molecular machine essential to all life, in a key transitional state that has long eluded researchers. Now, for the first ...

This image could lead to better antibiotics

June 28, 2013

(Phys.org) —This may look like a tangle of squiggly lines, but you're actually looking at a molecular machine called a ribosome. Its job is to translate DNA sequences into proteins, the workhorse compounds that sustain ...

Recommended for you

Genomes uncover life's early history

August 24, 2015

A University of Manchester scientist is part of a team which has carried out one of the biggest ever analyses of genomes on life of all forms.

Rare nautilus sighted for the first time in three decades

August 25, 2015

In early August, biologist Peter Ward returned from the South Pacific with news that he encountered an old friend, one he hadn't seen in over three decades. The University of Washington professor had seen what he considers ...

Why a mutant rice called Big Grain1 yields such big grains

August 24, 2015

(Phys.org)—Rice is one of the most important staple crops grown by humans—very possibly the most important in history. With 4.3 billion inhabitants, Asia is home to 60 percent of the world's population, so it's unsurprising ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.