Researchers at Rice University have published an unique approach to label individual proteins. Their creation has applications that can be used to track proteins at different time points, which is useful to observe instances of appearing and disappearing proteins at different cell cycle stages and to track individual protein expression.
Jonathan Silberg, a synthetic biologist on the team, believes that this technique will help researchers understand diseases better.
“Proteins are the business side of the cell,” Silberg said. “They provide structure and do a lot of the signaling within a cell. They give rise to a lot of the complexity we observe. In the future, our technique could help people understand the details of a disease by providing snapshots of proteins synthesized in specific cells at different times during development and allowing comparisons of healthy and diseased cells.”
In the cell, protein synthesis occurs through a complex process called translation. During this process, the nucleotide sequence of a mRNA (messenger RNA) is translated into an amino acid sequence of a protein. Though there are numerous proteins that are essential for translation to occur, one of them, the ribosome, provides the basic machinery for translation. The ribosome’s most notable function is to catalyze the linking of amino acids, specified by the mRNA, to form a protein. The amino acids are brought to the ribosome by transfer RNA (tRNA) molecules.
Emily Thomas led a team of scientists that improved upon prior publications to attach non interfering artificial amino acids (aAA) to tRNA. These noncanonical, not normally synthesized in the body, amino acids can be used as tags to track expression of the protein. The team’s breakthrough, was the discovery of a tRNA synthetase that only fuses the aAA to the tRNA in the presence of a chemical.
Thomas and her team used azidonorleucine (AnI), a derivative of norleucine, as their aAA to tag proteins in E. Coli. The aAA would only fuse to the tRNA if the tRNA synthetase was activated by a specific chemical. In the absence of that chemical, tRNA synthetase was not able to tag the protein. Synthetic biologists like to think of this as an engineered switch that is controlled like a computer program’s “AND gate.” The tRNA’s switch is turned “ON” in the presence of the chemical. In the “ON” condition, scientists are able to track expression of the protein.Thomas views this technique as a “protein spy.” “It spies on what proteins are being made inside the cell,” she said. “Current technologies just spy on everything, but I want to be more specific. I want more control over when I turn my spy on or off, so I can track only the cells I’m interested in.”
The technique provides scientists with a new tool to follow protein translation. The researchers discovery enables scientists to better detect cellular changes by spying on proteins and detect changes that underlie diseases. Silberg described the new discovery as “far out,” and compared their findings to exploring Mars.
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