Since 2007 the highly prestigious peer-reviewed journal Nature Methods annually crowns a “method of the year” to give credit to the most remarkable new method that had a wide-ranging impact on the scientific community in the respective year. For 2010 they selected optogenetics.
Neuroscientists are more familiar with this method than other scientists as most results so far come from their field. Not being a neuroscientist, I had never heard of optogenetics before. What could it be? As can be inferred from its name, it somehow must combine optics and genetics; it deals with genes and light. My first thought was that it might have to do something with vision and possibly how we perceive light, or maybe developing some novel way of treating vision disorders. Wrong. It actually is much cooler. Optogenetics is the technology of introducing genes encoding for light sensitive proteins into cells and then controlling a specific aspect of the cell by light!
Light sensitive proteins – the optics part
Light sensitive proteins are proteins that perform an action upon exposure to light. You simply shine light on the protein and it does something. Upon this light activation it might for example change its shape or bind to another protein in a cell. A lot of functions in a cell are based on such protein shape changes or binding of different proteins to each other. So upon shining a light on these proteins, they undergo some change that enables them to do some cool stuff. Much like a switch that is controlled by light. Switch the light on –> function on. Switch the light off –> function off. Or the other way round.
Getting the proteins into cells – The genetics part
The central dogma of molecular biology describes the normal flow of information in biology. DNA encodes for RNA encodes for protein. So to stably get the light sensitive proteins into the cells of your interest, you have to get the genes present on a piece of DNA into these cells. One way of how that usually happens is that you isolate that gene of interest from an organism, for example bacteria, then pack it into a virus and infect the target cell you want the protein to be in with that virus. The virus acts like a postal package… you put the interesting gene in it and deliver the virus to the destination, where the package (virus) gets opened and the gene unpacked. The regular cellular machinery in the target cell will then make protein from the introduced gene.
So what optogeneticists do is they take a special gene from somewhere else, they then might alter it a bit and send it nicely packed into the cell they are interested in. The cell then makes special proteins from this special gene and the special proteins in the cell do some neat little trick when they see light.
Yes! Big Deal! The little tricks the proteins can do in the light, like changing shape, cuddling together, or moving to a specific part of the cell can make the cell respond in a variety of ways, depending on the exact protein and the cell, and this is where it gets super cool. In neuroscience for example, this can lead to the opening of channels in cell walls, so that molecules can cross these barriers. This in turn can lead to activation of nerve cells and to a coordinated response of the animal. For example researchers could make a mouse with Parkinson’s disease walk regularly, make heart cells beat in response to light or make a fly try to escape whenever you shine a light on it. Here is the Nature Methods video about it.
Advantages over previous techniques – speed, precision, reversibility, invasiveness
What makes optogenetics so valuable is the spatial and temporal control that is possible with the combination of light and genetics as well as its reversibility and minimal invasiveness so that it works even in live animals. Previous methods that are used to study similar phenomena include photocaging (irreversible) or drugs/chemical activation (slower, more invasive). In addition, the speed and the spatial precision with which light can be turned on and off in a lab allows optogenetics to deliver much more defined signals than electric stimuli for example.
Basically, you can give amazingly well timed and defined instructions to cells, a feature that is especially valuable for neuroscience bit also for other areas.
image by greenmelinda
And it gets better
But there is so much more…
For instance, there are several light-sensitive proteins that react to different colors of light.
And you can take the light-sensitive part of one of these proteins and stick it on other proteins to make them light sensitive themselves. And you can do that with the parts that are activated by the different light colors… Now that expands the toolbox immensely.
The light signal can activate or inactivate, depending on how the light-sensitive part gets put on the protein.
The precision with which light can be controlled is amazing. Light can shine on only a part of the cell… and at the same time you can shine light of a different color on another part of the cell. Or you can turn the light on and off in patterns.
The light-sensitive proteins can be made in a way that they would only be present in a specific cell type, but not in others, and only at a specific time of that cell’s life.
Or think about using these tools in naturally transparent organisms like zebrafish…
And, once again: reversible and minimally invasive.
You can have different proteins in different parts of subsets of cells in their native environment reversibly and differentially activated or inactivated by shining light on the cells.
And yes, it gets even better again… scientists are already working on advancing the technique further. For example they try to make proteins that can react to a different color of light, one that can penetrate deeper into tissues like brain for example.
The possibilities for applications of this new technique, especially in combination with other techniques, seem to be endless.
Cheers, to the method of the year,