“Can we map large-scale systems like the
brain with molecular precision?” he asked.
Not if you can’t see what you’re doing.
To solve that problem, his team is pioneering
“physical magnification—blowing things
up to see them better.”
The scientists have found methods to physically inflate cells and tissues using the same chemistry that permits a baby diaper to absorb urine. Sodium polyacrylate swells with the addition of water, up to nearly 5 times its original size. Boyden’s team has invented “expansion microscopy,” which enables a regular microscope to attain super-resolution images.
Boyden said that work in the 1970s on responsive polymers led to this new approach, wherein specimens are fixed and labeled, forming a swell-able gel that can expand the sample, which is structurally disrupted with enzymes. The addition of water serves as an amplifier.
“Our hope is that one day we can visualize the structure of the genome,” he said. Displaying colorful slides of magnified cells and tissues, he quipped, “I can stare at these all day.”
His wit was also evident when he observed that this process “doesn’t work, of course, in live samples. Expanding something 20 times isn’t compatible with living.”
|Boyden (l) leads the MIT Media Lab’s synthetic neurobiology research group, which develops tools for mapping, controlling, observing and building dynamic circuits of the brain. It uses these neurotechnologies to understand how cognition and emotion arise from brain network operation, as well as to enable systematic repair of intractable brain disorders such as epilepsy, Parkinson’s disease and post-traumatic stress disorder.
Not that living specimens are off limits. Boyden and his colleagues are building robots that can perform automated patch-clamping, directed by computer, in the brains of live animals.
The talk, titled “Tools for analyzing and repairing complex biological systems,” covered mapping biological pathways, recording them and lastly controlling them; neurons can be made sensitive to light, using microbial opsins. This enables “single-cell resolution optogenetics.”
Boyden admits, “Controlling the brain is very hard to do.” But you have to start somewhere.
The hour-long talk, accessible only to HHS employees (much of the work is yet unpublished), is online at http://videocast.nih.gov/summary.asp?Live=16892&bhcp=1.—Rich McManus