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Why did you decide to focus your research on the ribosome?
GREEN: From a biochemist’s point of view, the ribosome is a beautiful system. You can easily manipulate it to study each of its functions in a detailed way. For example, you can give it an amino acid it needs, and the system will go. If you provide the wrong amino acid, it will stop. It’s also a beautiful machine. You look at it, and it clearly has all these moving parts. It’s stunningly complex.
In your recent paper, you show that the ribosome has a quality control procedure for finding errors during protein translation. Are errors and quality control a theme seen elsewhere in the cell?
GREEN: Yes. In DNA replication, there’s a polymerase that does a quality control step. Except in that case, if a mistake is found when a strand of DNA is being copied, the polymerase has to fix the mistake. In contrast, as our study showed, in protein synthesis, the quality control step doesn’t fix the error. It simply terminates production of the protein.
Why do errors occur at all? Why hasn’t the cell evolved a flawless mechanism for producing proteins?
GREEN: Fidelity costs the cell. It’s as though the cell does a cost-benefit analysis. It could improve its degree of fidelity, but at some point the cell doesn’t want to spend more energy on that.
Another factor is that some degree of inaccuracy can be to a cell’s advantage. Under times of stress, such as when a particular amino acid is in short supply, you might want the ribosome to be able to make a mistake—for instance, to be able to substitute an alternative amino acid for one that isn’t available.
Where would you like to take your research next?
GREEN: We want to understand how events outside of the ribosome control what goes on inside. There are all sorts of conformational rearrangements, or switches, that occur in the ribosome while making a protein. We are starting to find that outside factors “talk” to these switches. Some might say, “Slow down, we have too much protein X.” Or another factor might say, “Speed up, we need more protein Y.”