Josie Kishi

Josie Kishi, 31, co-developed Light-Seq, a technology that lets researchers look at cells under a microscope before sequencing them to analyze their genetic code. Previously those two techniques could not be done together. The technology will be a major boost to disease research, drug discovery, and treatment plans for cancer and other pathologies.   

“If you look at the standard methods, you’re faced with an impossible choice,” says Kishi. “You either use microscopy to measure cells—where cells are, how they are interacting with one another—or you use genetic RNA sequencing to understand what those cells are doing.”

Preparing a sample for one method tends to ruin it for the other. This is a significant loss, considering that they both provide unique insights. Combining the two would offer even more.

Kishi unraveled the problem by borrowing an idea from the computer industry, mimicking the lithography process used to print silicon chips. First, a sample is bathed in a solution containing tiny bits of barcode-like segments of DNA that only attach to specific regions of interest in the intact sample when intense light is focused on those regions. Then, after the samples are analyzed optically, the tissue can be sequenced using regular machines.

What’s more, the barcode labeling process can be done multiple times in a row, using different DNA barcodes—like underlining text in contrasting colors of ink to indicate different types of words—to label specific structures, cell types, or areas. In this way, multiple structures from the same sample can be matched to their unique genetic sequences and function.

Inspired by how quickly companies like BioNTech and Moderna produced vaccines during the covid-19 pandemic, Kishi co-founded Digital Biology. The company will use Light-Seq to investigate how disease forms, which could someday help scientists to identify which drugs are most likely to prevent cancer relapse, or treat specific conditions, in people with a given set of markers.