Small Molecules Light Up Gene Expression

The first small molecules that induce localized light-activated gene expression in large proportions of treated living cells are now available (ACS Chem. Biol., DOI: 10.1021/cb9002305). Scientists have developed several small molecules that induce cellular gene expression in response to light. The induced gene expression can then be detected by light microscopy. But the rate of induced gene-expression has been limited, with detectable responses in only a small fraction of treated cells, and no biological responses to the induced expression have been demonstrated. Now, Daniel J. Sauers and coworkers in John T. Koh’s group at the University of Delaware report that the tetracycline-based system RetroTET-ART, combined with a photocaged doxycycline, generates light-activated gene expression in about 85% of treated cells. In addition, the system can be used to direct the migration of cocultured cells in response to induced expression of attractive and repulsive molecules. The new gene-expression control and monitoring technique could be useful for studying expressed proteins that guide axonal development and for engineering artificial tissues, among other applications.