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Synthetic Biology Breakthrough at UCSF

Focusing a red laser at the periphery of a cell causes it to stretch outwards toward the illuminated point via a light-sensing "remote control" system. Courtesy HHMI.

Focusing a red laser at the periphery of a cell causes it to stretch outwards toward the illuminated point via a light-sensing "remote control" system. Courtesy HHMI.

For the first time, researchers at UCSF have succeeded in importing a light-controlled “on-off switch” from plants into mouse cells, creating engineered cells that can be trained to follow a beam of light or to stop and start on command. The findings were first reported in the September 13 online publication of Nature, along with a paper on similar research by a team at the University of North Carolina, Chapel Hill.

From UCSF’s press release: “Together, the papers are the first to demonstrate that plant light-switches can be imported into mammalian cells to control complex regulatory processes. The UCSF research is unique in developing a generic plug-and-play switch, based on protein recruitment, which can be wired to control diverse processes in many types of cells and organisms.”

Wendell Lim, PhD, professor in the UCSF Department of Cellular and Molecular Pharmacology and one of three senior authors on the paper, envisions a variety of uses for the new cellular technology, which he describes as a sort of “universal remote control.” With the ability to start and stop cell movement or to restrict movement to specific regions of a cell using brief pulses of laser light, “we can use this tool to better study how metastatic cancer cells move through the body,” Lim says on the website of the Howard Hughes Medical Institute, where he is also a researcher. “The technique also points to ways that we might use light to, for example, guide regrowing nerve cells so that they make the right connections” — across a broken spinal pathway in the case of spinal cord injury, for instance.

The research was carried out by Anselm Levskaya, a graduate student in both Lim’s laboratory and in the laboratory of co-author Chris Voigt, PhD, a synthetic biologist and assistant professor of pharmaceutical chemistry in the UCSF School of Pharmacy. (Earlier in his career, Levskaya collaborated with the UT Austin iGem team to develop a bacterial photography system, discussed in a previous post.) Levskaya imported a “light switch” found in plants, which utilizes light-sensing signaling proteins called phytochromes, into live mouse cells, installing them in a cellular pathway that controls cell motion. The resulting cells can be pulled by an external beam of dilute red light, pushed away by an external infrared beam, or turned off at will. Similar sensors have been programmed into bacteria and yeast cells, but this was a first in mammalian cells.

In addition to their medical significance, the findings give a boost to proponents of synthetic biology who seek to identify, manipulate, and deploy standardized biological “parts” in a variety of organisms to create complex systems not found in nature.

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