Optogenetics

Optogenetics is a relatively new discipline that deals with the control of genetically modified cells by light.

History

As the founder of a new branch of research of optogenetics applies Karl Deisseroth. One of the key pioneers in the development of optogenetics common Gero Miesenböck and Boris Zemelman be reckoned with their research from the years 2002 and 2003.

Description

It is with this technology is a combination of methods of optics and genetics, with the aim of certain functional events in specific cells or living tissues to ( gain-of -function ) or disable (loss -of-function ). In this case, light-sensitive proteins by genetic engineering by manipulating encoding DNA (ie, the corresponding gene) to be modified and then introduced into specific target cells or tissues. When exposed to light, it is then possible to control the behavior of the modified cells in this way.

So Optogenetics allows a specific and very rapid ( millisecond range ) control of precisely defined events in complex biological systems. Hereby studies at the protein level ( applications in molecular biology ), at the level of individual cells ( cell biology ) are made possible and defined tissues ( histology) or even at the level of freely moving mammals ( behavioral biology ).

The of the scientific journal Nature Methods, the " Method of the Year 2010" erkorene technology is being tested in animal models of Parkinson's disease and epilepsy.

Opto -genetic methods are already used today to explore different intracellular processes, such as the localization of proteins in specific regions of the cell or the production of specific molecules such as second messenger ( second messengers ), or control. This targeted modification of cellular signaling cascades in cell biology is undergoing an increase in knowledge about intracellular processes, as he was hardly imaginable a few years ago. Also in neurology, where the method was first developed, it allows previously unthinkable detailed insight into the workings of the nervous system and the brain.

Channelrhodopsin as an example of an opto -genetic switch

An example of how the optical genetics is used at the molecular level, the use of a genetically modified form of the Channelrhodopsins ( ChR2 ) as a " switch" molecule. Channelrhodopsins are inherently independent, light-gated ion channels. They are not so-called G- protein coupled receptors in spite of structural relatedness. It is now possible to extend into the intracellular C -terminal to replace the end of the ChR2 protein or to change ( modify ), without the function of the protein is affected as an ion channel. The genetically modified fusion proteins can then be introduced by means of a number of transfection techniques ( viral transfection, electroporation, gene gun ) in excitable cells such as neurons, where they are brought to expression ( production). Vitamin A, the precursor of the light-absorbing chromophore retinal in vertebrate cells usually already present, so that excitable cells, which express channelrhodopsin, can be easily depolarize by lighting. This in turn allows the use of modified channelrhodopsins, for example for applications such as the photo- stimulation of neurons. The blue-sensitive ChR2 in combination with the by yellow light - activated chloride pump halorhodopsin allow the switching on and off of neuronal activity within milliseconds.

If ChR2 labeled with a fluorescent label excited axons and synapses can be identified in the intact brain tissue by light. This technique can be used to elucidate the molecular events during the induction of synaptic plasticity. With the help of ChR2 extensive neuronal pathways have been mapped in the brain.

Is that the behavior of transgenic animals expressing ChR2 in a proportion of their neurons can be controlled without contact by intense illumination with blue light, has already been shown for nematodes, fruit flies, zebrafish and mice.