Kwanghun Chung wants to make it easy for scientists to take a molecular snapshot of the brain. The very best imaging technology available today allows inspection of just 10 or so biomolecules in 3-D. “It’s not enough,” says Chung, who hopes to render a complete picture of all of the hundreds of thousands of biomolecules at work inside the thousands of distinct cell types across a whole human brain.
A new assistant professor in MIT’s Department of Chemical Engineering, Chung started on a project to preserve subsets of neurons in brain samples and to isolate them in place for visualization while a postdoc at Stanford University. His proposal to preserve all the cells and, at the same time, make them transparent and permeable led to the development of CLARITY. This method shores up postmortem brain tissue using a chemical mesh and then dissolves all of the fat, which is what previously made it so hard to see into the brain. What remains is a transparent — yet perfectly intact — brain.
With the aid of molecular and structural markers, it is possible to take a visual voyage deep inside the “clarified” brain and see the structures, connections, individual neurons, and molecules at work inside them. “The good thing about CLARITY is that it’s not destructive,” Chung says. “You can use it over and over again, adding and removing molecular probes until you extract out all the information you want.”
During development of CLARITY, Chung was influenced by two of his colleagues, who shared with him their personal stories about siblings with autism. “I realized the impact brain disorders have on people’s lives and decided to focus my research on mapping the human brain,” he says. “There is huge room for neurotechnology development that can significantly accelerate the pace of discovery and the development of new therapeutics.”
As a participating researcher with MIT’s Institute for Medical and Engineering Science, Chung believes he is especially well positioned to continue on this path. “Through IMES, I can collaborate with engineers, neuroscientists, and doctors who see patients with brain disorders,” says Chung, who is also a principal investigator at the Picower Institute for Learning and Memory. In his new lab, Chung is working to make CLARITY scalable to human brains. His other main focus, in collaboration with researchers at the Broad Institute, is on extracting a complete collection of molecular information from intact three-dimensional brain tissue, a project akin to his earlier microfluidic embryo and cell trackers, only at a billion or so times the scale.
“Engineers really need to jump in with scientists and clinicians,” Chung says. “We need to work together to develop new tools to crack the brain.”