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Despite the importance to our health, the biology of how drugs work at the cellular level, remains largely a mystery.  In a recent Public Library of Science (PLoS One) article, Montana Molecular describes new diacylglycerol sensors to help unravel some of the mystery. This new assay technology has enormous potential to improve the tools used to find new drugs to treat pain, heart failure, neural disease, diabetes and immune disorders. Diacylglycerol is a key component of G-protein signaling and the G-protein coupled receptors are a target for nearly half of all drugs currently on the market.

In the past, a robust assay for diacylglycerol (DAG) has been elusive. By switching to a single circularly permuted fluorescent protein and a strategy of remixing to optimize the signal, Montana Molecular researchers achieved unprecedented results. This new generation of fluorescent diacylglycerol sensors uses a single green fluorescent protein, and can be coupled with a red fluorescent Ca2+ sensor, R-GECO, for simultaneous measurement of both second messengers in real time.

This work was done in collaboration with Robert Campbell’s group at the University of Alberta, and was funded in part by the National Institutes of Health, MSMFP and MBRCT from the Montana Department of Commerce, Alberta Innovates, the Canadian Institutes of Health Research, and the Natural Sciences and Engineering Research Council of Canada.