Scientists switch components in cell circuits: Possible new technolog...( SCIENCE. Lim's laboratory at UC...)

Lim's laboratory, at UCSF's Mission Bay campus, is interested in how the enormous diversity of signaling circuits observed in living cells have evolved. His research team and others have come to understand that like much in evolution, nature has repeatedly used the same or similar modular components for different functions.

"If you build some machine that is perfectly engineered for one function but it's not modular, it is inflexible -- it can only perform that one function," Lim says. "But if it's modular, you can replace one module and that can create a new function. That's apparently how many new cellular signaling proteins and circuits have evolved. It's very similar to how an engineer can make many different circuits from the same types of modular electronic components "

Over the course of evolution, Lim explains, cells have apparently gained new circuits say, a new way to respond to a hormone by re-mixing their modules of signaling proteins. The new research shows that it is possible to mimic what nature has done repeatedly.

Lim and his colleagues manipulated a naturally occurring signaling protein, known as N-WASP, which normally directs cells to move by promoting the build-up, or polymerization, of the protein actin. When the actin buildup pushes one edge of a cell, the cell moves in that direction.

Actin polymerization is normally controlled in the cell by two signals "upstream" of the N-WASP protein.

"We simply replaced the regions of the protein that detect the normal upstream inputs with novel protein modules that detect two unrelated inputs," Lim says. "We could show that the 'decision' to polymerize actin remained intact, but now under the control of these new input signals."

To accomplish the replacement, the scientists spliced together the genes that encode the new modules and those that encode the output module the module that drives actin polymerization into one composite gene.
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
25-Sep-2003