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genome positions as colorful dots

News feature: Revealing chromosome contours, one dot at a time

February 21, 2022
3D reconstruction of a nucleus. Each colour represents a different chromosome, and each dot is a gene location.
Credit: Y. Takei et al./Science

Nature interviews Cai Lab in this week's Technology Feature, describing how in situ microscopy works jointly with proximity ligation and sequencing to expand our understanding of the 3D world inhabited by our chromosomes. The article details how Long Cai had the inspirational thought that a genetic sequencer is fundamentally a microscope, from which he laid the theoretical groundwork for seqFISH and the giant leap made by former student, Yodai Takei, in applying it to DNA. Read the full article at Nature.com

"Caltech bioengineer Long Cai's approach to spatial genomics stemmed from a simple realization: "Fundamentally, a DNA sequencer is a microscope." Many modern sequencing machines decode DNA by incorporating fluorescently tagged nucleotide bases into the DNA as it is copied, reading those additions letter by letter. Cai figured: "Why take everything out of the cell, prepare it, and put it in the sequencer?" He wondered whether he could instead analyze nucleic acids right where they lie."

illustration of seqFISH+ process - mapping spatial location in the nucleus by creating a sequential barcode via fluorescent microscropy.
Credit: Nature