Massimo Scanziani is using light as a type of remote control to manipulate cells and tease out the daunting complexity of muscle, heart tissue, and particularly brain tissue.

The repertoire of light-switchable modules available for optogenetics studies is growing. “There's a Home Depot of different kinds of switches out there,” says Michael Ehlers, an HHMI investigator at Duke University Medical Center, where he studies the structure and dynamics of the synapses through which neurons communicate with one another. Deisseroth's group, for one, continues to stock the shelves with more and more optogenetic switches.

Their newest category of switches, the optoXRs, enable researchers to modify cells to respond to light as though they were being stimulated by neurotransmitters, such as adrenaline and dopamine. These switches combine a light-sensing rhodopsin component with the internal parts of a G protein-coupled receptor. That's a large family of receptors that trigger internal cellular responses to sensory, hormonal, neurochemical, and other stimuli arriving at the outside of the cell. For neuroscientists, optoXRs open entirely new research approaches for studying Parkinson's disease, schizophrenia, addiction, and other severe neurological problems, Deisseroth says.

		Lighting Up the Brain Hear Karl Deisseroth talk about where the field of optogenetics is headed.

Boyden and his colleagues are trolling the ever-enlarging library of genomic databases to diversify the optogenetic tool set. That's how he and his coworkers found Arch and Mac, two light-driven proton pumps (the first from a bacterium, the second from a fungus) that silence cells into which the researchers insert them when the switches are exposed to yellow and blue light, respectively. The scientists reported their initial work with them in a Nature paper on January 7, 2010.

Lim, at UCSF, is applying optogenetic methods to illuminate the localized, protein-protein interactions that underlie everything from turning genes on and off, to making cells more or less sensitive to stimuli, to cytoskeletal remodeling that alters a cell's shape or influences its movements.

Phytochrome B is a light-sensitive receptor in the mustard plant Arabidopsis thaliana that Lim is developing as a versatile molecular tool. In its normal role, the phytochrome enables the plants to respond to shade. When bathed in red light, for example, the phytochrome undergoes a shape change that leads to the alteration of gene expression in ways that cause the plant to grow toward sunnier patches of space.

In one audacious show of experimental control, Lim and his colleagues combine the phytochrome with an enzymatic component into modules so they can use light to trigger the polymerization of actin protein molecules in a cell. This results in localized changes in the cell's cytoskeletal framework, which determines the cell's shape. Using precision optics, the researchers can induce localized shape changes with enough finesse that Lim refers to the process as cell sculpting.

Denis Poroy / AP ©HHMI

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