MAP technology featured in Tech Crunch

MAP technology featured in Tech Crunch

This new brain-scanning technique is literally mind expanding

Sometimes it’s hard to tell the difference between science and technology ó almost all the time when it has to do with the brain. But this research from MIT that allows for vastly improved scans of the networks inside the brain is too cool to pass up, whether it’s tech, science, or somewhere in between.

Getting up close and personal with neurons and other brain cells is a science that people have been working on for a century and more. Mainly the problem is that they’re so darn small, and packed so tightly, and connect in so many places at once, that it’s hard to tell where anything’s going. We have ways of imaging the brain at various levels, but each is highly limited in its own way.

This new technique addresses several of the main problems. It’s called magnified analysis of proteome, or (conveniently) MAP. The summary from lead researcher Kwanghun Chung makes it sound almost too good to be true.

“We use a chemical process to make the whole brain size-adjustable, while preserving pretty much everything,” Chung says in an MIT news release. “We preserve the proteome (the collection of proteins found in a biological sample), we preserve nanoscopic details, and we also preserve brain-wide connectivity.”

MAP technology featured in MIT News

Imaging the brain at multiple size scales

New technique can reveal subcellular details and long-range connections.

Anne Trafton | MIT News Office
July 25, 2016

MIT researchers have developed a new technique for imaging brain tissue at multiple scales, allowing them to peer at molecules within cells or take a wider view of the long-range connections between neurons.

This technique, known as magnified analysis of proteome (MAP), should help scientists in their ongoing efforts to chart the connectivity and functions of neurons in the human brain, says Kwanghun Chung, the Samuel A. Goldblith Assistant Professor in the Department of Chemical Engineering, and a member of MIT’s Institute for Medical Engineering and Science (IMES) and Picower Institute for Learning and Memory.

“We use a chemical process to make the whole brain size-adjustable, while preserving pretty much everything. We preserve the proteome (the collection of proteins found in a biological sample), we preserve nanoscopic details, and we also preserve brain-wide connectivity,” says Chung, the senior author of a paper describing the method in the July 25 issue of Nature Biotechnology.

The researchers also showed that the technique is applicable to other organs such as the heart, lungs, liver, and kidneys.

The paper’s lead authors are postdoc Taeyun Ku, graduate student Justin Swaney, and visiting scholar Jeong-Yoon Park.

MAP paper published in Nature Biotechnology

The biology of multicellular organisms is coordinated across multiple size scales, from the subnanoscale of molecules to the macroscale, tissue-wide interconnectivity of cell populations. Here we introduce a method for super-resolution imaging of the multiscale organization of intact tissues. The method, called magnified analysis of the proteome (MAP), linearly expands entire organs fourfold while preserving their overall architecture and three-dimensional proteome organization. MAP is based on the observation that preventing crosslinking within and between endogenous proteins during hydrogel-tissue hybridization allows for natural expansion upon protein denaturation and dissociation. The expanded tissue preserves its protein content, its fine subcellular details, and its organ-scale intercellular connectivity. We use off-the-shelf antibodies for multiple rounds of immunolabeling and imaging of a tissue's magnified proteome, and our experiments demonstrate a success rate of 82% (100/122 antibodies tested). We show that specimen size can be reversibly modulated to image both inter-regional connections and fine synaptic architectures in the mouse brain.

Kwanghun Chung receives McKnight Technological Innovations in Neuroscience Award

Kwanghun (KC) Chung, investigator of neuroscience at the Picower Institute for Learning and Memory, core faculty of the Institute for Medical Engineering and Science, and an assistant professor in the MIT departments of Chemical Engineering and Brain and Cognitive Sciences, was selected to receive a 2016 McKnight Technological Innovations in Neuroscience Award for his work on “multi-scale proteomic reconstruction of cells and their brain-wide connectivity.”

Dr. Chung and his lab are developing new technologies to generate a comprehensive, high-resolution brain map, including one known as CLARITY (Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging / Immunostaining / in situ-hybridization-compatible Tissue hYdrogel), which renders tissues, like those within the brain, completely transparent. Chung gained international recognition for creating this breakthrough technology.

Current brain mapping is relatively low resolution and incomplete; Chung’s research will allow neuroscientists to interrogate many molecules, cell types, and circuits in single tissues. By utilizing a transparent brain image and additional biological techniques, an exceptionally detailed map of neuronal pathways can be made which were previously inaccessible.

Dr. Chung is also working to combine new tissue processing technologies with genetic labeling techniques. Chung expanded on the CLARITY technology to develop SWITCH, which uniquely allows for up to 22 different proteins to be imaged in a 3D array. Dr. Chung hopes that this high resolution, comprehensive brain mapping will accelerate the pace of discovery in a broad range of neuroscience applications and enable scientists to characterize animal disease models in a fast and unbiased way.

“I am very grateful about the opportunities that this award will provide,” said Chung. “With the resources we will pursue our high-risk project in developing new technologies for integrated, high-resolution imaging and phenotyping of the brain.”

“It has been a thrill to see the ingenuity at work in developing new neurotechnologies,” said Markus Meister, PhD, chair of the awards committee and the Anne P. and Benjamin F. Biaggini professor of biological sciences at Caltech. “This year’s awards reflect the great untapped potential that still exists in visualizing the connectivity and function of the brain.”

The Endowment Fund predominantly supports work seeking to advance the ability to monitor, manipulate, analyze or model brain function. The awards do not support research based primarily on existing techniques. Technologies developed with McKnight support must ultimately be made available to other scientists.

The McKnight Endowment Fund for Neuroscience will grant $600,000 over two years for the award, with three research projects each receiving $200,000 to expand the range of technologies for studying the brain and its diseases and to make these new technologies available to the field of neuroscience. Since the technology awards began in 1999, the Endowment Fund has contributed more than $12 million to innovative technologies for neuroscience.

The next round of awards will be announced in October, with letters of intent due December 1, 2016. For more information about the awards, please visit https://www.neuroscience.mcknight.org/the-awards/technology.

Kwanghun Chung awarded Packard Fellowship

Kwanghun Chung awarded Packard Fellowship

The David and Lucile Packard Foundation named 18 of the nation’s most innovative early-career scientists and engineers as recipients of the 2015 Packard Fellowships for Science and Engineering. Each Fellow will receive a grant of $875,000 over five years to pursue their research.

Sung-Yon Kim Receives Donald B. Lindsley Prize in Behavioral Neuroscience

Sung-Yon Kim Receives Donald B. Lindsley Prize in Behavioral Neuroscience

The Society for Neuroscience (SfN) will award the Donald B. Lindsley Prize to Sung-Yon Kim, PhD, of the Massachusetts Institute of Technology. Supported by The Grass Foundation, the prize recognizes an outstanding PhD thesis in the area of general behavioral neuroscience.