"If we need an iron-sulfur cluster to get fluorescence, then we have a reporter for those clusters in living cells," Silberg said. The custom proteins can be used to analyze cells for signs of diseases involving iron-sulfur irregularities.
"That's why I'm really excited about this. This is a screen that will allow fundamental biology that nobody can do right now," he said. "And it has high potential for helping us find real treatments for disease."
Silberg said iron and sulfur were present in Earth's primordial stew even before there was oxygen. "The atmosphere was anaerobic when life evolved, and iron and sulfur were plentiful. These metalloclusters are easy to build, so you can imagine that if the chemistry's simple and the molecules are around, proteins will evolve to do a lot of chemistry using iron-sulfur clusters.
"Then photosynthetic organisms evolved and started to produce oxygen. Iron is very easily oxidized, so aerobic organisms evolved all this machinery to protect it, to repair it. That's the machinery we're studying."
Measuring clusters in live cells is a breakthrough of great interest to the American Heart Association, which partly funded the study. "They gave us money to build more tools," Silberg said. "They're interested in Friedreich's ataxia (which can lead to heart disease), but they also want to know if we can develop ways to image other proteins with metalloclusters."
In this study, he said, "We actually answered a fundamental biological question -- that glutaredoxins associate using metalloclusters in vivo. No one's ever showed that in living human cells."
Refining the tools has high priority in Silberg's lab now, but in the long ter
|Contact: David Ruth|