The U-M team, led by Rehemtulla and Brian D. Ross, Ph.D., professor of radiology and co-director of the center, reports they have discovered a way to turn the light "off" until a drug causes a cell to start dying.
They did this by attaching luciferase to another protein, a portion of the receptor for the hormone estrogen. The estrogen receptor, or ER, is known to squelch the action of attached proteins, such as luciferase's light-releasing chemical reaction.
Then, they added a "switch" that could turn the luciferase on -- but only when the cell was in the self-destruction process called apoptosis.
The ability to make images of apoptosis in real time could help pharmaceutical companies and academic researchers screen new drugs rapidly, for all types of diseases that are characterized by over-growing cells or cells that die too soon.
For example, scientists are studying drugs that can keep brain cells from dying after a stroke, a process that occurs through apoptosis and can cause permanent disability. Conversely, cancers and blood disorders that stem from over production of certain cell types are often treated with drugs aimed at killing extra cells.
But the U-M team believes its technique could also help with drug discovery and testing in diseases where other molecular mechanisms besides apoptosis are involved.
The team's discovery hinges on the ability to turn the luciferase glow off until a cell process occurs. They developed this "light switch" by inserting a tiny section of protein between the luciferase and the estrogen receptor (ER) protein. Called DEVD, the section is known to be targeted for cutting by an enzyme called caspase-3 -- the key agent that sets off apoptosis. Because caspase-3 is most active when cells are dying, the team felt that it
'"/>
Contact: Kara Gavin
umhsmedia@umich.edu
734-764-2220
University of Michigan Health System
17-Dec-2002