An Inside Look at Research that Glows
One particular room on the School of Medicine campus contains more than 30,000 glowing fish.
Rows of tanks in the FINZ Center hold the many zebrafish
that are used for research in 20 laboratories
at the Johns Hopkins Medical campus.
This IGM sponsored Functional Investigation in Zebrafish (FINZ) Center contains more than 2,000 tanks that hold fish for more than 20 research labs.
But at a medical campus, why fish? Why not use the mouse, which has the obvious benefit of being closer to human in that it’s at least a mammal?
“Zebrafish are the simplest vertebrate organism on which we can easily do genetic and chemical screens,” says Michael Parsons, an assistant professor of surgery and one of three faculty directors of FINZ. “We can do these screens on flies, but they are invertebrates, and therefore less related to the human genome.” Parsons and co-director Steven Leach, the Paul K. Newmann Professor in Pancreatic Cancer, use zebrafish to study the pancreas; Parsons focuses on how insulin-producing beta cells develop and how they regenerate, and Leach studies the biology of pancreatic stem cells and pancreatic cancer.
“We can house tens of thousands of fish in the facility because of their small size—an adult fish is less than 2 inches in length,” says Leach. “Moreover, their eggs fertilize externally and the embryos are semi-transparent, so we can observe their development under a microscope in real-time.”
This day-old zebrafish embryo glows because it contains green
fluorescent protein or GFP, a protein naturally found in jellyfish.
The fish glow because they’ve been engineered to contain a piece of DNA that encodes a protein naturally found in jellyfish, called GFP for green fluorescent protein. This transgene incorporates into the fish’s genome and is passed to offspring, leading to a stable line of glowing fish.
Not all the fish glow green and their cells don’t just start glowing automatically, cautions Andy McCallion, FINZ co-director, IGM member and associate professor of molecular and comparative pathobiology. (In other words, don’t try this at home.) In fact, there are several ‘flavors’ of GFP, all engineered to glow a slightly different color. “Different proteins excite at slightly different light wavelengths,” he says and emit light with different colors. The first step in making a glowing fish is for researchers to figure out which sequences direct gene expression in cells of interest.
Zebrafish embryos are semi-
transparent, which allows real-time
observations of their development
using a microscope.
McCallion studies how genes are switched on and off, in particular the roles that DNA between genes play in gene control. These gene switches can be hard to identify. So McCallion combines a fragment of DNA he thinks contains a switch with the GFP gene and puts this into fish. If the suspected DNA acts as a switch, GFP is turned on and cells glow. “Basically the fish act as live test tubes,” says McCallion.
“GFP is essentially non-toxic to the fish, as long as they are not exposed to too much light,” says Leach. In fact, Yorktown Technologies of Austin, Texas has been selling fluorescent zebrafish as pets since 2003.
While these tiny fish have gained traction over the years, Hopkins researchers have not abandoned the classic mouse model. “Some things are reproducible in mice, some are reproducible in fish,” says Parsons. “Like anything in science, you have to ask the right questions of the right organism.”
--by Ally Burton
Learn more about FINZ at the zebrafish core's website.
Learn more about Andy McCallion’s research here:
GENETIC FISHING EXPEDITION YIELDS SURPRISING CATCH IMPORTANT TO MAMMALS
MORE “FUNCTIONAL” DNA IN GENOME THAN PREVIOUSLY THOUGHT