Negative Thinking

GUIDING LIGHTS: Channelrhodopsins from algae such as Guillardia theta (center; false-color image) are endowing optogenetics with novel abilities.DR DAVID HILLThe paper
E.G. Govorunova et al., “Natural light-gated anion channels: A family of microbial rhodopsins for advanced optogenetics,” Science, doi:10.1126/science.aaa7484, 2015.

Channel Surfing
Channelrhodopsins (ChRs) from green algae paved the way for optogenetics research in neuroscience and other fields. These membrane ion transporters are light sensitive, and importing them into neurons has given scientists unprecedented control over neuronal activity. The 50 or so known algal ChRs only transport positive ions, however, which trigger action potentials. Only one ChR from an Archean species and engineered algal ChRs can transport anions, which suppress neuronal firing by hyperpolarizing neurons, and neither is as fast or sensitive as the natural algal channels. “[ChRs] enabled fairly efficient activation of neurons, but neural inhibition was limited to much lower-efficiency tools,” says molecular biologist John Spudich of the University of Texas Medical School at Houston.

An Alternative Source
In their search for ChR diversity, Spudich and his colleagues looked to another type of alga called a cryptophyte. They examined the genome of Guillardia theta and cloned three genes that resembled those for known ChRs. After expressing two of the genes in human embryonic kidney cells, “the first thing we saw was an unusually large current,” says Spudich.

The Natural
The researchers found that these channels were natural anion transporters, and when expressed in rat neurons, they are 10,000 times more sensitive than engineered anion channels. “You have to search in nature to find these wonderful tools,” says Wayne State University’s Zhuo-Hua Pan, who is starting to use G. theta’s channels in experiments.

A Brighter Future
Spudich is not stopping at G. theta. He plans to look for more anion channels that will expand the utility of optogenetics. “There are many cryptophytes out there.”