Super-res pioneer highlights optical tools' relevance for neuroscience

Xiaowei Zhuang was surprised by the invitation to present one of four Presidential Special Lectures at the Society for Neuroscience's 2017 Annual Meeting (Neuroscience 2017; held November 11-15 in Washington, DC). She does not consider herself an expert in neuroscience, she explained—and then she proceeded to captivate the audience with examples of how optical imaging has facilitated discoveries in neurobiology, and promises even more.

Along the way, she paid homage to other super-resolution imaging pioneers, including Sam Hess, developer of fluorescence photoactivation localization microscopy (FPALM), who will present a webcast tomorrow (November 28, 2017) on advances in FPALM and their impact on life sciences. And Zhuang illustrated the important contextual information provided by optical live-cell imaging that other microscopy/nanoscopy methods do not deliver.

Optically aided neuroscience

Zhuang, perhaps best known as co-developer of stochastic optical reconstruction microscopy (STORM),¹ is a Harvard University professor and Howard Hughes Medical Institute investigator. Her talk, Illuminating Neurobiology at the Nanoscale and Systems Scale by Imaging, attracted nearly a quarter of the 30,000 attendees to Neuroscience 2017. It presented two techniques: the "old" (circa 2006) super-resolution fluorescence, and a newer (2015) high-throughput single-molecule imaging method for transcriptome analysis in single cells.

She first described how super-resolution approaches—patterned illumination (such as stimulated emission depletion, or STED), and single-molecule (such as STORM)—allow nanometer-scale fluorescence imaging of cells and tissues. Further, she explained how optically enabled illumination of the dynamics of a cell's fine "ultrastructure" provides greater insight than electron microscopy allows.² Images showing that axon cytoskeletons are made of regularly spaced ring-like structures, not criss-cross patterns (as previously thought), helped make the point.

From super-res to MERFISH

Then, Zhuang introduced the newer method, multiplexed error robust fluorescence in situ hybridization (MERFISH). Developed in her lab, this massively multiplexed single-cell transcriptome imaging approach can profile the expression of thousands of genes—in situ, in a spatially resolved manner—in individual cells (a transcriptome, by the way, represents all messenger RNA molecules expressed in an organism's genes). In an overnight session, for instance, the technique can handle 50,000 cells, and map the spatial organization of the various cell types. This capability should be particularly useful for the BRAIN Initiative's Cell Census project, which NIH had announced just a couple of weeks before.

Zhuang may not be an expert in neuroscience, but she and her collaborators certainly have a lot to offer neuroscientists. And as she made clear, optical methods are critical tools for neuroscientists' toolboxes.

REFERENCES

1. M. Rust, M. Bates, and X. Zhuang, Nat. Methods, 3, 10, 793–795 (2006).

2. S. H. Shim et al., Proc. Nat. Acad. Sci., 109, 35, 13978–13983 (2012).