“Programmed” Cells Could Combat Cancer

Originally Published MDDI January 2004

R&D DIGEST

John Conroy

Drawing a parallel between human cells and electronic circuits, scientists at a California university have “programmed” cells to mimic sensors or computers. The cell-engineering technology could be used to combat cancer or create organs such as an artificial pancreas, the researchers say.

A team led by Wendell Lim, PhD, an associate professor of cellular and molecular pharmacology at the University of California, San Francisco (UCSF), manipulated a signaling protein that directs cell movement. Known as N-WASP, the protein promotes the accumulation, or polymerization, of another protein called actin. When accumulated actin pushes one edge of a cell, it causes that cell to move in a certain direction.

Normally, two signals coming before the N-WASP protein control actin polymerization, Lim points out. By creating new proteins to control cell movement, the UCSF team demonstrated that the signaling proteins are modular and interchangeable.

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

The researchers spliced the genes that encode the new modules and the genes that encode the output module for actin polymerization into one composite. They then conducted tests of the protein encoded by the composite gene to see how it responded to new stimuli. 

Similar to electronic components, this modularity could allow scientists to create cells “with novel and diverse circuits and behavior.” Lim says it may be possible to design “a signaling switch that promotes cell death only when triggered by proteins found in tumor cells.”

Lim insists this modular replacement method is simpler than another technique for engineering proteins that involves making many specific mutations. The new method also “can yield proteins capable of integrating multiple signals, mimicking the sophisticated behavior required for cell functions.”

Conducted in Lim's laboratory at UCSF's Mission Bay campus, the research study proves that modular components in living cells perform different functions in nature, the team leader asserts. A machine engineered for one function is inflexible, he notes. However, replacing one module in a modular machine creates new functions. “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.”

Lim concludes: “Cells do computations and process information in much the same way computers do, so maybe we can ‘reprogram' cells the way we can reprogram computers.”

Based on their work with Lim, two graduate students have been named finalists in the Collegiate Inventors Competition sponsored by the National Inventor's Hall of Fame. They are John Dueber and Brian Yeh. Lim, Dueber, and Yeh are coauthors of the study with Ka-Yam Chak, a postgraduate researcher.

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