NSF awards EAGER grant to expand use of temperature-activated protein switches in neurons

Troy Zars, Mirela Milescu, and Lorin Milescu, faculty members of the Division of Biological Sciences and the Interdisciplinary Neuroscience Program at the University of Missouri, have been awarded an Early Concept Grant for Exploratory Research (EAGER) from the National Science Foundation to expand the use of a temperature-activated protein switches in neurons. The new technology could lead to a better understanding of brain disorders in humans.

"Thermogenetics is a discipline of study that is expanding the horizons of brain research by allowing us to precisely control specific neurons in the brain and measure behavioral changes," said Zars, who is principal investigator of the grant. "So far, there are a relatively small number of proteins that do respond to temperature in way that is useful for work in flies. Our goal is to identify more of these special proteins, so that the technology can be used in other organisms."

In one series of experiments, the scientists will comb through a large family of genes, called gustatory receptors, in search of a natural source of these special temperature-activated proteins. Most relevant to the scientists will be identifying genes with different temperature properties, of which they expect to find several.

In parallel experiments, the researchers also will engineer their own temperature-sensitive protein. They will do this by breaking down a receptor gene into its constituent parts, removing the thermosensor (the part that is responsive to temperature), and installing it in another protein.

"Once we identify the building blocks of these particular proteins, we can create chimeric proteins by making mutations or switching parts of receptor proteins so that we can get an array of proteins that we can turn on or off at different temperatures," said Mirela Milescu.

They will deliver the natural and engineered proteins into fly neurons to test the effects of changes in temperature on neural activity using advanced imaging techniques and software developed by Lorin Milescu.

The researchers expect the new proteins to be responsive to a range of temperatures and thus useful across organisms.

EAGER grants support the federal BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, a project that aims to map all the neurons in the brain. The two-year $300,000 awards support short-term, proof-of-concept projects.