A Unlikely Star of Science

Jonathan Freedman Looks to Microscopic Roundworms to Document the Effects of Toxic Chemicals p.5

  The NTP chose Freedman to evaluate the roundworm as a substitute animal model for large-scale testing of chemicals’ effects on growth and development because “Jon’s lab is very highly regarded,” said associate director Portier.

   As his multimillion-dollar contract begins, Freedman has seen his Nicholas School lab group triple in size from about four or five people to 15 in more than a year. Along with new hires came boxes and boxes of specialized equipment that have given his part of the university some of the ambience of high-tech industry.

  Much of the work is being done by software-controlled robotic machines. Rows of tubes automatically dispense hot agar gel to support the bacterial colonies that the worms use as food. After the agar cools and solidifies in the sunken wells where the animals will live, machines add drops of bacteria.

  Tubes also measure out chemicals at various levels of dilution and place those in the wells. Meanwhile, another machine, called a “biosorter,” sends worms through a centrifuge before sucking them into tiny passages where they are counted and sorted one by one while a laser beam assesses each animal’s length as well as diameter, age, color and general health. Then the biosorter dispenses the right worms to the correct wells for a specific experiment.

  There are 96 wells arrayed on each plate, the basic testing unit of this highly automated operation. Between 10 to 50 nematodes are placed in each well depending on the test. “We may put worms that have just hatched into a well and watch them grow,” Freedman says. “Or we’ll do another experiment where we put an adult animal in and see how many offspring it makes and count the offspring and see how fast they grow.”

  Another variation is to create varieties of transgenic worm lines, each line bearing a different gene that fluoresces green under stress. “That way in a 96-well plate each well would have a different strain of transgenic worm that could respond to a chemical,” he says. “So you just put the same chemical in all the wells to find out which gene is turning on.”

  While the computer-aided robotic equipment can efficiently track movements of chemicals, agar and worms, right now much of the follow-up analysis is being done by humans using special microscopes.

  Freedman also is collaborating with Rachel Brady—a research scientist and founding director of the Visualization Technology Group at Duke’s Pratt School of Engineering and an adjunct associate professor at the Department of Computer Science—in an effort to computer-automate time-consuming visual analyses.

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