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Forget the flea circus. Two teams of scientists have independently developed the beginnings of a technologically sophisticated worm circus. They combined genetic engineering with a novel tracking approach in order to illuminate specific cells in the microscopic worm C. elegans and control the organisms’ movement, making the animals slither forward or backward. With a flash of light, they could even stimulate the worms to lay eggs.

While these feats sound entertaining, the technology does have a practical purpose. It will help researchers learn how basic neural circuits work together in sensing and responding to the environment, such as when a worm smells food and crawls toward it.

Central to these worm tricks is optogenetics—a genetic engineering technology that allows scientists to control the activity of neurons with light. Researchers add genes for light-sensitive proteins to certain cells in the organism. They can then use specific colors of light to activate or silence particular cells and circuits, which in turns reveals the role that those cells and circuits play in the broader nervous system.

“We use an ordinary LCD projector to essentially remote-control the worm’s mind and movement,” wrote Hang Lu, associate professor of chemical and biomolecular engineering at the Georgia Institute of Technology, in an e-mail. “We can make worms ‘dance’ or do ‘head nod’ or ‘tail wag’ by controlling the contraction pattern of the muscles;  we can control the ‘mind’ of the worm by shining light on certain sensory neurons to make the worm ‘think’ that it’s being touched in the head or the tail, or it should initiate backward movement or continue forward movement.”

Christopher Fang-Yen, assistant professor of bioengineering at the University of Pennsylvania, says optogenetics is a “kind of remote-control device for neurons.” Fang-Yen was part of one of the research teams.  

While scientists can genetically target light-sensitive proteins to specific subsets of cells, this approach has limitations. It’s difficult to activate or silence single cells, for example. So teams at Harvard University and the Georgia Institute of Technology developed a method to track individual cells in worms as they crawled around a petri dish.

“Instead of a floodlight, we use a series of spotlights to track the animal,” says Fang-Yen, who carried out the research while a postdoctoral researcher at Harvard University in collaboration with graduate student Andrew Leifer. “We have a computer analyze the image and project a beam only on the tissues we want to stimulate, giving us spatial and temporal control in a freely moving animal.”

Ed Boyden, leader of the Synthetic Neurobiology Group at MIT and one of the creators of optogenetics, says the research “provides a valuable proof-of-concept of how digital light-processing technologies can be used to augment the molecular toolbox. Even when it is impossible to achieve true molecular specificity, it may be possible to aim light precisely at defined cells.”

Scientists have developed other methods for controlling animal behavior, such as implanted electrodes and a microchip, which have been used to remotely control a flying beetle. But one advantage of the nematode C. elegans is that it is transparent; shining light over the animal triggers neural activity. It also has a simple and well-defined nervous system. The worm’s 302 neurons have all been precisely mapped out.

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Credit: Georgia Tech/Hang Lu
Video by Georgia Tech/Hang Lu, edited by Brittany Sauser

Tagged: Biomedicine, genetic engineering, optogenetics, worms

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