MerMAIDs: The hunt for new channelrhodopsins

Mining natural oceanic diversity reveals new channelrhodopsin activities to be applied in optogenetics
MerMAIDs: The hunt for new channelrhodopsins

Channelrhodopsins are microbial rhodopsins that directly convert absorbed light into ion fluxes across cellular membranes by opening conductive pores, and are widely used as optogenetic tools for manipulating neuronal activity. Known for science for about 15 years already, only 3 subtypes of channelrhodopsins are currently recognized. However, these cation- and anion-conducting channelrhodopsins were all discovered in laboratory-cultured microbial algae. 

            To better define channelrhodopsin diversity and to look for new channel activities, we set to look for channelrhodopsin sequences in different metagenomic datasets with special emphasis on the Tara Oceans publically available sets. To our big surprise, new sequences (now dubbed MerMAIDs) that do not belong to any of the known channelrhodopsin families were detected in the Indian, Atlantic, and Pacific Oceans and in the Mediterranean Sea. The surprise became even bigger when their electrophysiology was measured in HEK cells (see setup below). Not only that they conduct anions, but the new channels also show surprisingly short periods of conductivity, which facilitates temporally precise neuronal silencing even under continuous presence of light. 

The electrophysiology setup used to record MerMAIDs’ channel activity. Note the trace of MerMAID1 on the screen. (photo credit: Johannes Oppermann)

Our findings show the power and potential of combining metagenomics and electrophysiology for the discovery of new rhodopsins activities. We are now in the process of searching more environmental datasets, on the DNA and RNA levels, in order to find new channelrhodopsins and novel biophysical properties.

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