Souped-up fish facility boosts drug discovery and testing

closeup of zebrafish-20150526_ZebraFishCeremony-60The care and feeding of more than 250,000 zebrafish just got better, thanks to a $4 million grant from the Massachusetts Life Sciences Center to upgrade Boston Children’s Hospital’s Karp Aquatics Facility. Aside from the fish, patients with cancer, blood diseases and more stand to benefit.

From a new crop of Boston-Children’s-patented spawning tanks to a robotic feeding system, the upgrade will help raise the large numbers of the striped tropical fish needed to rapidly identify and screen potential new therapeutics. It’s all part of the Children’s Center for Cell Therapy, established in 2013. We put on shoe covers and took a look behind the scenes. (Photos: Katherine Cohen)

The zebrafish aquaculture system has six blocks housing a total of more than 3,000 individual tanks, tracked by a touchscreen control system that monitors temperature, pressure, pH, salinity and other variables. (Zebrafish biologist Christian Lawrence can also operate the controls from his phone.) The fish can absorb test drugs directly from their water and are relatively cheap: one recent project that would cost $3 million in mice cost only about $150,000 in the fish, says Leonard Zon, MD, founder and director of the Boston Children’s Hospital Stem Cell Program.

The aquaculture system has six blocks housing a total of more than 3,000 individual tanks. The touchscreen control system monitors temperature, pressure, pH, salinity and other variables in each tank. (Lawrence can also operate the controls from his phone.)

The set of 10 new zebrafish “love tanks” below provide optimal conditions for breeding. The blue textured bottom creates cozy spawning channels and can be raised to make the water more shallow (which the fish prefer). The eggs can then be collected from the water. “We can collect up to 20,000 eggs in a few minutes,” says Lawrence. Boston Children’s has licensed the tank design to Tecniplast under the name iSpawn.

These zebrafish "love tanks" provide optimal conditions for breeding. The bottom can be raised to make the water more shallow, and the textured bottom creates cozy spawning channels. The eggs can then be collected from the water. "We can collect up to 20,000 eggs in a few minutes," says fish biologist Christian Lawrence.

A proper diet is essential to zebrafish development and growth. This feed production system grows nutritious plankton known as rotifers to supply the zebrafish larvae.

This feed production system supplies larval zebrafish with rotifers--nutritious plankton important to development and growth.

The rotifers need careful feeding, too. These tanks below are growing bioengineered algae, high in the long-chain fatty acids that help rotifers thrive.

Feeding the food source: These tanks are growing bioengineered algae that the rotifers consume, boosting their nutritional value.

This robotic feeder–the facility has three–reads each tank’s barcode and delivers a pre-programmed pinch of food.

This robotic feeder reads each tank's barcode and delivers a pre-programmed pinch of food.

This washer heats to 180 degrees F to sterilize tanks and other equipment. Since zebrafish are very sensitive to most detergents, which strip off their protective mucus layer, the washer uses a special surfactant-free product.

This washer sterilizes the tanks and other equipment, using a special surfactant-free detergent. (Zebrafish are very sensitive to most detergents, which strip off their protective mucus layer.)

Strange as it may seem, zebrafish have genomes that are surprisingly similar to ours, making them excellent first-pass disease models. The Karp Aquatics Facility is already hosting explorations on the origins of melanoma, the engraftment of transplanted stem cells and the effects of various gene manipulations.

This isn’t the only grant the Massachusetts Life Sciences Center has given to advance research at Boston Children’s. Earlier this year, the hospital received nearly $2.2 million from the MLSC to create a Human Neuron Core, which will model a variety of neurobehavioral disorders in neurons made from patients’ own cells.