Research Spotlight
Voilá! New laboratory tool makes proteins vanish faster
By Aditi Risbud
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Turn it up, turn it down and, if you want to, turn it off.
Scientists at the School of Medicine have developed a faster way to temporarily eliminate a targeted protein within a cell. The technique could potentially be used by researchers worldwide.
"We've invented a new technology and want to see scientists use it," said Thomas Wandless, PhD, assistant professor of molecular pharmacology and senior author of the study published in the Sept. 8 issue of Cell. "It enables new experiments and allows researchers to ask questions that they were not able to ask before."
Indeed, a number of laboratories at Stanford and elsewhere have already had success using the new technology.
Biologists often figure out the role a protein plays in the cell by disrupting production of the protein to see what happens. Traditional techniques stop a gene from sending a message to make more protein. This is done by temporarily deactivating the gene itself. That means any protein that already exists lingers in the cell long after the gene is turned off.
The new strategy removes the lag time inherent in other systems. It relies on making a slight alteration in the gene that codes for the particular protein. This altered gene produces the normal protein but with an added region called a destabilization domain. Although this added region doesn't interfere with the normal role of the protein, it does act like a switch to make that protein less stable.
What flicks the switch is a small molecule that scientists add to the cell or deliver in food to laboratory animals. When that small molecule is present, it binds to the destabilization domain and allows the protein to carry out its normal role in the cell. In the absence of this molecule, the destabilizing domain causes the protein to rapidly degrade.
The ability to remove the protein from a cell and then allow it to return means scientists can view the effects of a protein at a specific moment in a cell's life, shedding light on processes such as metabolism or immune response.
"This method reversibly regulates protein function by simply adding or removing a cell-permeable small molecule, and could potentially be used by anyone in the biology community," said Laura Banaszynski, a chemistry graduate student who is the first author of the study.
Benefiting the most from this method are experiments in which the concentration of protein is crucial to its function, or those in which the time scale of the desired experiment is short, Banaszynski said.
For example, if a scientist is studying how a protein functions at a certain point in a cell's life, he or she can remove the small molecule from the cell in a lab dish just for that short amount of time. Studying how the cell responds to suddenly losing that protein can reveal what role the protein normally plays in the cell.
Graduate students Lystranne Maynard-Smith and Lisa Ooi, along with staff researcher Ling-chun Chen are co-authors on this study. The research was funded by the National Institutes of Health.
Aditi Risbud was a science-writing intern in the Office of Communication & Public Affairs at the School of Medicine.
Posted: 09/29/06