Caption: William Stauffer
By Anita Srikameswaran
The National Institutes of Health (NIH)-funded BRAIN Initiative is celebrating the successes of multiple research centers, including a team from the University of Pittsburgh and Carnegie Mellon University, that are forging the next generation of molecular tools and technologies to accelerate understanding of how the brain works and how to repair it when it misfunctions.
Eight papers representing the work of 29 North American institutions that are part of the Armamentarium for Precision Brain Cell Access were published in the May 21 issues of the journals Neuron, Cell, Cell Genomics and Cell Reports Methods. The effort was launched four years ago to create a molecular toolkit for neuroscientists, and has created gene delivery systems that can reach different neural cell types with exceptional accuracy.
“With these delivery systems, we can now access and manipulate specific cells in the brain and spinal cord – access that was not possible before at this scale,” John Ngai, director of the NIH BRAIN Initiative, said in a press release.
Each research team developed techniques that employed harmless adeno-associated virus, or AAV, to deliver chosen genes into specific cell types, allowing researchers to manipulate cellular activity to better determine their roles in brain circuitry.
“Unlike the liver or other organs where cells are similar and perform the same functions, the brain has thousands of distinct cell types that work together to make us who we are,” said William Stauffer, assistant professor of neurobiology at Pitt School of Medicine and Armamentarium senior investigator. “These molecular tools could make it possible to understand the circuitry that allows humans to remember, feel and reason.”
That knowledge could show the way to repairing schizophrenia, Parkinson’s disease, Alzheimer’s disease and other devastating brain disorders, he said.
With Carnegie Mellon collaborator and cosenior author Andreas Pfenning, the Stauffer team used machine-learning approaches to reveal cell type specific “enhancers”—genomic regulatory elements—that make it possible to examine the function of specific cell types in the dorsolateral prefrontal cortex of the nonhuman primate (NHP) brain. Described in the scientific journal Neuron, their project uses a unique approach that identifies cell-type specific enhancers in the genome of rhesus monkeys. This is necessary, Stauffer said, “because the dorsolateral prefrontal cortex emerged during primate evolution.”
“This means that many of the neural circuits that are affected in schizophrenia, Alzheimer’s disease and other challenging disorders do not exist in rodent brains,” Stauffer said. “If our goals are to treat human neurological diseases, NHP research is irreplaceable.”
Other Armamentarium teams developed AAV delivery systems to target excitatory and inhibitory neurons, spinal cord neurons affected in amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy, and the brain’s blood vessel cells, according to NIH.
Stauffer credited program officer Douglas S. Kim, of the National Institute of Mental Health, for spearheading the Armamentarium effort, which awarded the Pitt/CMU team $6.8 million three years ago to conduct their research.
The team included three lead investigators, including Jing He, who was a postdoctoral fellow in the Stauffer lab and now is an assistant professor at Emory University; BaDoi Phan, an MD/PhD student in the Pfenning lab, and Willa Kerkhoff, a graduate student in the Stauffer lab.
“This type of technology development research is incredibly interdisciplinary and requires many different talents and types of expertise,” Stauffer noted. “All the Armamentarium projects are large-scale collaborations. There is no one investigator who can cover this much ground.”
Media contact: HSNews@pitt.edu