An approach involving genetically modified neurons that fluoresce when active—in combination with an optical microscopy method—offers a substantial speed improvement over current drug development approaches. The Harvard University (Cambridge, MA) team that developed the method hopes their work will eventually enable them to study how neuronal signals move in living animals.
The researchers produced a protein that glows when exposed to the electrical signal in a neuron. They infected lab-cultured brain cells with a genetically altered virus containing the protein-generating gene. Once infected, the cells began manufacturing the protein.
The protein sits in the membrane that surrounds each neuron. This membrane is made of an active substance, and when a neuron fires, the voltage reverses briefly and activates other neurons downstream. This allows the team to see how quickly signals spread through a neuronal network, and whether the signals change as the cells change.
The research promises to help illuminate how electrical signals move through the brain and other tissues—which could aid the development of drugs and other therapies. The current method for testing drug compounds that affect ion channels (proteins that govern heart and brain activity) is a multi-step process that can take an hour or two for each data point. But the team’s optical microscope method enables them to test the efficacy of a drug on a cell in a few seconds, enabling testing of thousands or even hundreds of thousands of compounds in the time it now takes to test one to 10.
The method could also facilitate the study of genetic conditions such as depression and heart disease. Using stem cells, researchers can culture cells that are genetically identical to a patient with a known genetic predisposition for a particular condition, then study how signals move through those cells.
1. J.M. Kralj et al., Nat. Meth., doi:10.1038/nmeth.1782 (2011).