Alexander Gottschalk: Remote controlling nematodes with light

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Alexander Gottschalk has been Heisenberg Professor at the Goethe University in Frankfurt am Main since March 2010. Source: Goethe University

19.08.2010  - 

The role of this understated man in one of the greatest challenges of science could prove to be immense. With the help of an emerging field of research – optogenetics – the biochemist Alexander Gottschalk at the University of Frankfurt is investigating the nervous system of the nematode Caenorhabditis elegans. The unique aspect of his work: Using light, he can activate individual nerve cells in the animal, allowing conclusions to be drawn on neuron function. Gottschalk is thus hoping to gain insights into the human nervous system and the development of the brain.

The mammalian nervous system is possibly the most complicated network in the known universe: Every single one of the 100 billion neurons in the human body can be interconnected with up to 10,000 other nerve cells. Aided by optogenetics, the understanding of these vast networks as an interaction of a larger number of circuits is improving dramatically. “We can use light pulses to switch individual nerve cells on and off,” says Gottschalk, “to then observe, how the organism behaves.” On his laptop, Gottschalk has numerous films of nematodes that change their behaviour under irradiation with different sources of light, making them stretch or bend, make wave-like movements, or suddenly change direction.

Just by switching on a source light, Alexander Gottschalk can control the nerve cells in a nematode specimen, and induce it to make specific movements.Source: Goethe University

Nerve cells with on/off switch

In a sense, optogenetics allows a switch to be installed in individual nerve cells. These switches are made from proteins that react differently to light at specific wavelengths. The protein channelrhodopsin, for example, responds to blue light, and activates a nerve cell, halorhodopsin, that responds to yellow light, and which in a sense switches the neuron off. Gottschalk's laboratory has now succeeded for the first time in piloting these light-controlled proteins in a living organism: The scientists simply smuggled the genetic information for the protein into the nematode germ line cells. The nerve cells in the offspring can now be switched on or off with the right kind of light.

As a model animal, the nematode Caenorhabditis elegans is underestimated, says Alexander Gottschalk.Source: Goethe University

The nematode: a born all-rounder

In his thesis, the biochemist Gottschalk originally investigated a molecular biological topic related to messenger RNA in yeast. “At some point, however, I wanted to get away from unicellular organisms,” he says. Neurobiology, namely the interaction of large numbers of nerve cells, fascinated the young scientist. “The exciting part, of course, is how individual cells pass on the signals.” Somewhat accidentally, in the search for main research topic he hit upon the nematode. “The nematode nervous system is simple, but also proportionally large,” explains the researcher.

Every nematode has only 302 nerve cells with 7000 interconnections. It’s a simple set-up, but it’s enough for the worm to be able to perceive smell, taste, and touch. “There has not been enough recognition in Germany of how a large number of relevant processes can be derived from this worm,” thinks Gottschalk. Following his doctoral studies, he initially returned the US where he could gain some much-needed expertise in the area of nematodes. At the end of 2003, he returned to Germany as a junior professor. He has been Heisenberg Professor at the Goethe University in Frankfurt am Main since March.

Human nerve cells can in principle also be disabled

With the help of optogenetics, Gottschalk hopes to understand from first principles the functioning of the nematode nervous system. Although this system is much simpler than that of humans, there are some major similarities. In principle, in the next step it could even be possible to manipulate human neurons using optogenetic techniques. For example, nerve cells that spiral out of control in particularly strong forms of epilepsy or Parkinson's disease could be immobilised. “In the case of Parkinson's disease, so-called brain pacemakers are used to electronically stimulate specific nerve cells,” says Gottschalk. However, it is not possible to determine which cells exactly are being stimulated. “Using optogenetics, this could be done extremely selectively.”

Author: Ute Zauft