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Researchers import light response trait from plant cells to mammalian cells
09-22-2009, 03:23 AM,
Researchers import light response trait from plant cells to mammalian cells

Researchers import light response trait from plant cells to mammalian cells

Erin Podolak

The ability for plants to respond to light stimuli to control cell function has been genetically encoded in mouse cells.

Researchers at the University of California San Francisco (UCSF) have genetically encoded mouse cells to respond to light, a trait previously seen only in plants. The encoded cells can be trained to follow a beam of light, or stop movement on command.

Researchers described the ability as an “on-off switch” for the cell controlled by exposure to light. The finding could lead to potential breakthroughs in cancer research, cardiovascular research, and nerve growth.

“This is a powerful tool for cell biology and cancer research,” said Wendell Lim, director of the Cell Propulsion Laboratory at UCSF and the University of California, Berkeley. The laboratory is part of the National Institutes of Health (NIH) Nanomedicine Development Center.

The researchers at UCSF published their findings in the Sept. 13 advance online edition of the journal Nature. The research from UCSF was complemented by a paper on similar research led by Klaus Hahn, professor in the department of pharmacology at the University of North Carolina Chapel Hill.

Together the papers are the first to document the importation of plant “light-switches” into mammalian cells to control the regulatory processes of the cells. The breakthrough at UCSF is significant because the researchers developed a generic “plug-and-play switch,” based on protein recruitment. The switch can be programmed to control processes in many types of cells and organisms.

“If you have a controllable ‘light switch’ that is generic enough to use in multiple cell functions, it gives you the ability to control where and when a cell moves, using a simple beam of light, and control what it does when it gets there,” said Lim.

Where and when proteins appear in the cell governs many cell processes, says Lim. In instances where the processes are based on a complex network of signals, as is the case in cancer patients, it will be helpful to have an “on-off switch” to insert into the process.

The research was a collaborative effort between three UCSF laboratories at the NIH Nanomedicine Development Center. Researchers at the Lim laboratory worked in conjunction with the lab team of associate professor of pharmaceutical chemistry Christopher Voigt, which uses synthetic biology to create light switches and sensors in bacteria, and that of professor of biochemistry Orion Weiner, which uses microscopy to study guided cell movement. All three labs are affiliated with the California Institute for Quantitative Biosciences at UCSF.

The research was conducted by Anselm Levskaya, a graduate student in the Lim and Voigt laboratories. Levskaya looked to plants for proteins that could function as light sensors in mammalian cells, since plants are known to utilize phytochromes, light-sensing proteins, to control cell processes. He tested the hypothesis that phytochromes could be genetically engineered into mammalian cells with a specific function—in this instance, cell movement.

Levskaya isolated a pair of interacting proteins, PhyB and PIF, which have the ability to be turned on and off easily. Levskaya then imported the cellular signaling system into live mouse cells in a cellular pathway that controls cell motion. Levskaya found that the altered cells could be pulled by an external beam of diluted red light, or pushed away by an external infrared beam.

“We’ve been able to use similar light sensors to program bacteria and yeast cells to follow a chain of if-then commands,” said Voigt. “What’s remarkable is the ability to, first, do this in mammalian cells, and secondly, find a method to turn them off again after they’ve performed their function.” The ability to control exactly when a disruption in a cellular pathway occurs, for how long, and when it will stop is a significant breakthrough for researchers, said Voigt.

The new finding could have a variety of therapeutic applications in the future, including the ability to guide nerve cells to reconnect across a broken spinal pathway, said Lim. In the near future, the new method could help facilitate research into the complex regulatory processes involved in diseases like cancer and inflammation.

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