Using largest grant in its history, Salk Institute will lead $126 million effort to map the aging human brain

Brain illustration

With a five-year, $126 million grant from the National Institutes of Health, a team led by scientists at the Salk Institute for Biological Studies in La Jolla has launched a new project that aims to describe the cells that make up the human brain in unprecedented molecular detail, classify brain cells into more precise subtypes and pinpoint the location of each cell in the brain. What’s more, the team will track how those features change from early to late life.

The goal is to better understand how neurotypical human brains work and age. The project — the Center for Multiomic Human Brain Cell Atlas, part of the NIH’s Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative — also intends to establish a baseline against which scientists will be able to compare brains with neurological or psychiatric conditions such as Alzheimer’s disease, autism, depression and traumatic injury.

“The brain map we develop could help point disease researchers in the right direction. For example, we could say, ‘That’s the ... specific subset of neurons, in that part of the brain, where a molecular event goes awry to cause that disease,’” said center leader Joseph Ecker, director of the Genomic Analysis Laboratory at Salk and a Howard Hughes Medical Institute investigator. “And ultimately this information might help us design gene therapies that target only the cell populations where the treatment is needed, delivering the right genes to the right place at the right time.”

In addition to Ecker, the center includes Margarita Behrens, a research professor at Salk; Bing Ren of UC San Diego; Xiangmin Xu of UC Irvine and Ting Wang of Washington University in St. Louis.

Salk will be awarded about $77 million of the center’s funding, making it the largest single grant the institute has received in its 62-year history.

In the Center for Multiomic Human Brain Cell Atlas, researchers will examine 1,500 brain samples (30 human brains, 50 regions each). The center is concerned mostly with epigenetics — the molecular events that influence whether genes are turned “on” or “off” in a given cell type or at a particular time — rather than genetic sequences of each cell. The center also will take into account which cells live where. Location is important because cells talk to one another, Ecker said.

“Essentially, we want to take millions, even hundreds of millions, of brain cells, learn everything we can about their epigenetics ... and project them in a spatial context so we can see where these cells live and understand how all of the cells in any brain region are organized, and at any age,” Ecker said.

“At the moment, we have almost no data like that for the human brain.” ◆