Researchers Can Stop and Start Genetic Transcription in a Flash

It's been ten years since the Human Genome Project announced that it successfully sequenced the human genome, but there is still much to be learned about how our 20,000 genes work to achieve our complex physiology. The field of molecular biology may already have its so-called "central dogma," which describes the transcription of DNA into RNA and RNA’s subsequent translation into the proteins that compose us, but simply watching the process doesn’t help us understand it the way getting in there and manipulating it ourselves could.

Thankfully, techniques to manipulate the processes with accuracy and precision are steadily popping up. One of the latest, from researchers at Harvard and MIT, is described in a paper to be published online in Nature on July 23.

The technique is an extension of optogenetics, a nascent set of technologies that rely on proteins whose properties change in response to light. It utilizes naturally occurring compounds assembled into new molecular contraptions, which enables a fairly unprecedented control of gene expression.

From previous experiments, the researchers knew that a protein called CRY2, originally found in a small flowering plant called Arabidopsis thaliana, binds to a CIB1 as a response to light. They suspected that if they could strategically attach another protein of interest to CIB1, they could activate this other protein indirectly through activating the CRY2. It turns out they were right.

The attached proteins of interest–which in this case are either transcription activator-like effectors (TALEs) or transcription repressor proteins–were shown to promptly initiate or terminate gene transcription.

Because different genes have different sequences of DNA associated with the initiation and termination of their transcription, the TALE or repressor proteins tested by the researchers were customized to act on different sequences. The researchers found that a single pulse of light was sufficient to affect the transcription levels, and the effects of the treatment were evident within 30 minutes for both transcription initiation and termination.

Silvana Konermann, a graduate student at MIT and co-lead author of the paper, said, “Cells have very dynamic gene expression happening on a fairly short timescale, but so far the methods that are used to perturb gene expression don’t even get close to those dynamics.” Using this new technique, researchers could swiftly boost or stop gene transcription on nearly 30 different genes.

The authors of the paper believe that their work will be used to explore the deleterious effects of gene manipulation on normal brain functioning. Further experimentation using this technique has the potential to lend great insight into how complicated disorders like autism and schizophrenia wreak their unfortunate effects in the brain.