Zebrafish may help speed drug discovery

January 17, 2012
This is Dr. Jeffrey Mumm, biologist in the Medical College of Georgia at Georgia Health Sciences University. Credit: Phil Jones, GHSU Photographer

Tiny zebrafish just may give scientists one solution to information overload in the search for new drugs therapies.

High throughput screening, which uses robotics and computers to rapidly screen drugs, genes or proteins, to identify, for example, that are best at destroying cancer or restoring insulin-producing cells. The technology has both revolutionized and stymied research, said Dr. Jeffrey Mumm, biologist in the Medical College of Georgia at Georgia Health Sciences University.

While the decade-old technology can screen 100,000 compounds in a day, there is no efficient next step for whittling to a manageable number the resulting say, 2,500 compounds that on first blush appear to have potential. Consequently, has actually stalled, creating a scientific "indigestion," Mumm said. Drug failure rates and discovery costs, on the other hand, have escalated.

"The next best thing to do is probably take all the compounds and put them into an that mimics the disease you are trying to cure but nobody has that kind of budget or would know where to start with that number of candidates," Mumm said.

One solution is pairing zebrafish with reporter-based assays that make certain parts glow, according to Mumm's research published in the journal . He calls it Automated Reporter Quantification.

"It's a way to cut to the chase rather than having to make educated guess about which of the 2,500 compounds are really of interest," said Mumm. Zebrafish, which start out as that are fully functioning by day four, already are an invaluable research model for a wide variety of diseases, such as Mumm's efforts to regenerate cells in the face of of the eyes or pancreas.

To produce a model of , for example, he uses a single drug to destroy insulin-producing cells; 24 hours later, he knows those cells are gone because the glow is gone in the transparent .

Now, he can leave the fish in the well plates, which look like plastic ice trays with cubes about the size of pencil tops and come in multiples of 96. The individual wells enable him to quickly reassess the impact of the thousands of compounds identified by high-throughput screening in a living specimen. Simply put: Does the glow come back? The next step becomes logical and doable: study the 20 or so compounds that continued to show promise in a mouse model. These steps to the fish then mouse, called biological validation, have been a real bottleneck in science post high-throughput screening, Mumm said. "This is going to give you much more thorough information about how compounds affect the overall physiology of a living being," Mumm said.

He noted that reporter-based assays number in the thousands so what they can help find is essentially limited only by the imagination.

He's used one to monitor a major signaling pathway that consistently shows up in cancer. "We hooked the pathway up to a reporter that told us whether it was on or off, then tested whether we could modulate it over time and, sure enough, it was very easy to do," Mumm said. "Name the cancer and basically you have WNT activated so there is a huge effort in cancer therapeutics to try and essentially shut it down."

Explore further: Small molecules inhibit growth of human tumor cells

Related Stories

Small molecules inhibit growth of human tumor cells

April 13, 2011

Researchers from the Cancer Institute at NYU Langone Medical Center have identified three novel small molecules that interrupt a crucial cellular communication pathway that regulates many aspects of development and cancer. ...

Recommended for you

An accessible approach to making a mini-brain

October 1, 2015

If you need a working miniature brain—say for drug testing, to test neural tissue transplants, or to experiment with how stem cells work—a new paper describes how to build one with what the Brown University authors say ...

Tension helps heart cells develop normally in the lab

October 1, 2015

The heart is never quite at rest, and it turns out that even in a lab heart cells need a little of that tension. Without something to pull against, heart cells grown from stem cells in a lab dish fail to develop normally.

Dormant viral genes may awaken to cause ALS

September 30, 2015

Scientists at the National Institutes of Health discovered that reactivation of ancient viral genes embedded in the human genome may cause the destruction of neurons in some forms of amyotrophic lateral sclerosis (ALS). The ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.