A fully genetically-encoded approach to light-activated transcription is getting closer now that a new, generalizable method of light-switchable protein interactions has been published. In Nature’s advance online publication, Spatiotemporal control of cell signalling using a light-switchable protein interaction, Anselm Levskaya of the Voigt lab at UCSF and co-authors demonstrate inducible, reversible control of protein binding, localization and signalling in mammalian cells.
When asked about the possibility that this could be used in-vivo, Levskaya said
The only real caveat for in-vivo work is delivery of the non-native PCB tetrapyrrole. From the literature and my experience with cell culture I suspect it shouldn’t be hard to just administer it directly to animals to get saturating levels for holoprotein formation. It might even be possible just to feed animals Spirulina (where it comes from). There’s nutrition literature that suggests their livers are capable of freeing PCB and getting it into the blood stream.
Expression of genetic tools that control neural activity (Channelrhodopsins, Halorhodopsins, DREADDs) in functionally defined populations, such as neurons that are active during a particular task or thought, is the next big leap that needs to be made in systems neuroscience. This may be achieved by combining an imaging technique to identify active neurons, such as G-CaMP3, with photo-switchable transcription. The technique presented in the above paper is one promising avenue which may lead to cell-specific photo-switchable transcription. Once robust versions of these tools are in place, scientists will begin to work out the complex and thrilling processes of reverse-engineering and manipulation of specific thoughts and memories, at least in mice and rats.