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CHRONICLE
PAGE 1 OF 2 TOOLBOX: A Trick of Light by Amber Dance
miniSOG, a protein label used in microscopy, can also trigger cell death on demand.
Seika Takayanagi places a dish of millimeter-long worms under a blue lamp in a darkened microscope room. At first, the worms squirm across the plate, leaving S-curved tracks behind them.
But 15 minutes later, when she switches off the lamp, something has changed. The tiny Caenorhabditis elegans worms are curled up, sluggish. The blue light started a process that kills a specific portion of their motor neurons. Within a few hours, those neurons, which enable the worms to move, start to disintegrate. By tomorrow they will have vanished—exactly what Takayanagi wants.
Worm in Regular Light
Worm in Blue Light When worms with miniSOG attached to their mitochondria are exposed to blue light, they become sluggish. From PNAS (2012) 109: 7499-7504.
How does killing cells help Takayanagi, a graduate student in the lab of Yishi Jin, an HHMI investigator at the University of California, San Diego (UCSD), understand biology?
Suppose you were an alien trying to understand the sport of soccer. You could bench different positions in turn—the goalie, the forwards, and so on—and see how well the team performed. By analyzing what was missing, you could figure out each player’s role.
Scientists use a similar strategy in the lab, eliminating parts of a living system one by one to figure out what they do. In collaboration with Roger Tsien, also an HHMI investigator at UCSD, Jin’s group accomplishes the cellular assassination by using a molecular bull’s-eye they situate inside the cells. The target is a small protein called miniSOG (short for mini-singlet oxygen generator). Jin and her colleagues add the gene for the miniSOG protein to the cells, which make the protein. The miniSOG protein attaches itself to the mitochondria, organelles that generate the cell’s energy and are essential for survival.
When miniSOG protein takes in blue light, it converts ordinary oxygen into a short-lived, excited state called singlet oxygen, which reacts with and changes the molecules around it. The singlet oxygen destroys the mitochondria’s delicate machinery. The scientists don’t know how this event kills the cell, but damaged mitochondria typically release toxic molecules.
