How to Build a Worm, in 3-D High Definition

By Jennifer Bell,

Thursday, September 11, 2014


Stunning movies captured in the lab of computational biologist Zhirong Bao reveal how cells divide, grow, and move around, as in a carefully choreographed dance, during the development of a nematode worm embryo.


This time-lapse movie shows a nematode, a type of worm, developing from an embryo of four cells to a hatchling of precisely 558 cells in just 14 hours. The green nuclei reveal each individual cell of the embryo dividing, growing, and moving in a carefully choreographed dance. The orange spots that appear halfway through the movie are cells switching on a gene that instructs them to become gut cells. Just a few cells light up initially, and then the tube of the worm’s digestive tract materializes.

The simplicity of the nematode and its predictable pattern of development make it a perfect test case for new advanced imaging technology developed by computational biologist Zhirong Bao of the Sloan Kettering Institute’s Developmental Biology Program. His goal is to uncover the secrets of how complex tissues such as organs and tumors develop by tracking each cell and the genes directing them, minute by minute.

It’s something that researchers in many fields of biology have dreamed of, but until recently, tissues in live animals could not be visualized at high enough resolution, and computational tools were not able to analyze vast image datasets.

Every Cell, Every Gene, Every Minute

The new technology uses cutting-edge microscopy to capture high-definition, 3-D snapshots each minute. The image data are processed by software developed by Dr. Bao and his team to trace each cell and determine precisely when and where each gene is turned on or off. From these results, computer algorithms build a complete model for how a tissue or organ develops — a sort of biological instruction manual.

Dr. Bao believes this automated approach can dramatically speed the pace of discovery in the study of complex biological processes that rely on many interacting cells.

“In validating our technology in the worm we were able to study 200 genes and produce a model of how the worm develops,” he says. “Researchers have been studying worm development for 30 years and have discovered 30-40 key regulatory genes. In one experiment we can recapitulate all of this information and go beyond.”

His team is now collaborating with researchers around the world to apply the technology to investigate more complex creatures, including zebrafish and mice. Ultimately he hopes the technology can be used to study the intricate interactions between cancerous and noncancerous cells that cause tumors to grow and spread.

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