Optical Tools for Analyzing and Repairing Complex Biological Systems
To enable the understanding and repair of complex biological systems such as the brain, we are creating novel optical tools that enable molecular-resolution maps of large scale systems, as well as technologies for observing and controlling high-speed physiological dynamics in such systems. First, we have developed a method for imaging large 3-D specimens with nanoscale precision, by embedding them in a swellable polymer, homogenizing their mechanical roperties, and exposing them to water – which causes them to expand isotropically manyfold. This method, which we call expansion microscopy (ExM), enables scalable, inexpensive diffraction-limited microscopes to do large-volume nanoscopy, in a multiplexed fashion. Second, we have
developed a set of genetically-encoded reagents, known as optogenetic tools, that when expressed in specific neurons, enable their electrical activities to be precisely driven or silenced in response to millisecond timescale pulses of light. Finally, we have collaboratively developed strategies to image and record fast physiological processes in 3-D with millisecond precision, and are using them to acquire neural activity maps with single cell resolution in living brain circuits. In this way we aim to enable the systematic mapping, control, and dynamical observation of complex biological systems like the brain.