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October 1, 2014
CHAPEL HILL, NC – The National Institutes of Health (NIH) announced the first round of funding for research dedicated to the BRAIN Initiative, including a $2.85-million, three-year grant to three UNC researchers who will build the next generation of DREADDs – a groundbreaking tool used for brain research developed by Bryan L. Roth, MD, PhD, the Michael Hooker Distinguished Professor of Protein Therapeutics and Translational Proteomics in the UNC School of Medicine.
DREADD, which stands for Designer Receptor Exclusively Activated by a Designer Drug, allows researchers to manipulate a specific kind of cell surface receptor so that it responds only to a specific kind of drug. Using this method, researchers can study precisely what happens in the brain when just one kind of G-coupled protein receptor is activated. Not only is this a novel way to study basic biological mechanisms of these commonly targeted receptors inside the brain and individual neurons, but it’s also a tool scientists can use to study specific effects of drugs in various regions of the brain.
Current treatments often have global effects on cells throughout the brain. Roth’s method, which has been sited and used by hundreds of neuroscientists since he first published his work in the Proceedings of the National Academy of Sciences in 2007, allows scientists to noninvasively home in on particular cellular signaling pathways important to neuropsychiatric disorders.
The other two principle investigators on the new grant are Thomas Kash, PhD, assistant professor of pharmacology in the UNC School of Medicine; and Jian Jin, PhD, associate professor and Director of the Medicinal Chemistry Center for Integrative Chemical Biology and Drug Discovery in the UNC Eshelman School of Pharmacy.
“DREADDs are essentially a useful set of tools, and like any tools they can be improved,” said Roth, who is also a professor in the UNC Eshelman School of Pharmacy and member of the UNC Neuroscience Center and the UNC Lineberger Comprehensive Cancer Center. “This BRAIN Initiative grant will be used to improve DREADDs with the ultimate goal that we can develop precisely targeted treatments for a host of neuropsychiatric disorders, such as autism, addiction, depression, anxiety, schizophrenia, seizure disorders, Alzheimer’s, and Parkinson’s disease to name just a few. DREADDs are also broadly useful as a synthetic biology platform for non-neuropsychiatric diseases, such as cancers.”
This week, the NIH announced $46 million in grants to more than 100 investigators to create new tools, technologies, and methods to explore and answer questions about the brain’s complex neural circuitry. The end goal is to use new discoveries to kickstart the creation of more effective treatments and cures for brain disorders, which the World Health Organization has estimated affect more than one billion people around the world.
As part of the NIH announcement, NIH Director Francis Collins, MD, PhD, said, “There’s a big gap between what we want to do in brain research and the technologies available to make exploration possible. These initial awards are part of a 12-year scientific plan focused on developing the tools and technologies needed to make the next leap in understanding the brain. This is just the beginning of an ambitious journey and we’re excited about the possibilities.”
For the UNC grant, Roth’s lab will use cells in culture to spearhead the creation of novel DREADD technologies. Then Thomas Kash’s lab will evaluate the effectiveness of the new and improved methods in animal models.
“We’ll be able to show how Bryan’s tools can be useful in different brain contexts; we’ll be able to research various signaling pathways throughout the brain,” said Kash, who is also a member of the Bowles Center for Alcohol Studies and the UNC Neuroscience Center.
The final stage is headed by Jian Jin, a member of the UNC Lineberger Comprehensive Cancer Center, will develop new compounds that will allow researchers to even more precisely activate the G-coupled receptors of individual cell types in the particular brain regions.
Some of these compounds will allow researchers to use a pulse of light to activate a receptor and then study the cascade of cellular signals that occur. Also, Jin’s lab will develop compounds for potential use in humans with the goal of translating this technology for human therapeutics and diagnostics
The BRAIN Initiative (Brain Research Through Advancing Innovative Neurotechnologies), which was announced by the White House in April 2013, includes a more than $110-million commitment to furthering brain research and deepening out understanding of the human brain.
This is a blog dedicated to users of DREADD. This is Bryan L. Roth’s website, which includes recent papers. Roth is also the director of the NIMH Psychoactive Drug Screening Program. Read more about Thomas Kash's research on his website.