Studies of biological systems will benefit from a robust method to collect molecular information over an entire organism at high spatial resolution. We have developed a method to physically expand fixed tissues of the nematode model C. elegans with high isotropy, while allowing simultaneous detection of fluorescent proteins, DNAs and RNAs at sub-cellular resolution. We demonstrate the utility of this method for analyzing neuronal connectivity, transcriptomic profiles and other structural features of the entire animal.

The biological relevance of 3D genome organization is increasingly recognized. Established methods for measuring genome-wide chromatin organization use next-gen sequencing as a proxy for spatial measurement. These methods are difficult to integrate with other ome-wide measurements, tissue context, and morphology in single cells. Measurement of chromatin genome-wide in situ would address these issues. I will propose two approaches for this, both rooted in expansion microscopy and in situ sequencing, and describe progress toward realizing them.