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MIA Talks

Optics-free spatio-genetic imaging with DNA microscopy

February 13, 2019
Zhang Lab, Regev Lab, Broad Institute

Complex cell populations, from the brain to the adaptive immune system, rely on diverse gene variants, somatic mutations, and expression patterns for some of their most essential functions. This genetic heterogeneity not only endows intrinsic properties to individual cells, but it also often operates at the level of inter-cellular interactions. Technologies that jointly resolve both gene sequences and the spatial relationships of the cells that express them therefore have a key role to play in deepening our understanding of tissue biology. In this talk, I will introduce DNA microscopy, a new imaging modality that operates by encoding pairwise distances between biomolecules in a sample directly into a DNA sequence library using a stand-alone chemical reaction. I will then present experiments demonstrating that, with these distances encoded, the positions of biomolecules and cells can be computationally inferred by DNA sequence analysis. DNA microscopy requires neither micromanipulation nor specialized equipment and leverages the power of commercial sequencers. Because its imaging power derives entirely from diffusive molecular dynamics, DNA microscopy constitutes a chemically encoded microscopy system.