Intriguing accident leads Keene State lab to study how flatworms can help spot human disease. (Flatworms?)

  • Jason Pellettieri, a biology professor at Keene State College, turned an accident involving flatworms into a research project studying models to understand human disease. William Wrobel / Keene State College

  • Keene State biology Prof. Jason Pellettieri, right, with two research assistants, J.P. Duston, middle, and Casey Kimball, left, in their flatworm lab. June 7, 2016. William Wrobel – Keene State College—

  • Casey Kimball photographs flatworms as part of lab research, June 7, 2016. William Wrobel – Keene State College—

  • Flatworms under standard laboratory conditions (brown) are pictured with flatworms subjected to intense light exposure (de-pigmented), along with a schematic representation of a porphyrin molecule (pink). Keene State College—

Published: 6/14/2016 2:55:15 AM

Louis Pasteur once commented that in science, “fortune favors the prepared mind,” meaning you’ve got to be smart to recognize dumb luck.

An interesting example of this is playing out at Keene State College, where biology professor Jason Pellettieri and his students are studying small aquatic worms to understand some rare human diseases, and are getting some hefty research funding to support them. They’re doing this because an error during an introductory biology class produced an interesting anomaly (the “dumb luck” part of the equation), which raised interesting questions that you or I wouldn’t have thought to ask (the “prepared mind” part).

“We have a dozen people in the lab working full-time, mostly on this project,” said Pellettieri, an associate professor in the biology department at Keene State, which isn’t the first place in New Hampshire you’d name when asked to discuss biology research.

The lab is studying a species of flat aquatic worm – officially S. mediterranea or planarian but often known, unimaginatively, as flatworms – to develop a model that will let us better understand a group of rare diseases that can cause extreme sensitivity to light, facial hair growth and even hallucinations. Their research paper “Light-induced de-pigmentation in planarians models the pathophysiology of acute porphyrias” was published May 31 in eLife, a nonprofit, online research publishing venture designed to speed up the expensive and slow model of journals.

Incidentally, I was surprised to see that Pellettieri is listed as final author on the paper, not the first one. Six current or former Keene State students are named before him, as well as two folks from a Canadian hospital who collaborated with the work. Pellettieri said this order reflects the fact that the work was actually done by students, notably lead author Bradford Stubenhaus, who started and drove the project.

Anyway, on to the story.

It starts with a general education course Pellettieri called “Stem Cells and Regeneration,” which covered some basic biology and lab work for non-science majors. It’s about as far from research-level biology as college gets.

“Most of these kids are taking the course essentially because they have to, so I approach it like a science outreach activity, to generate interest and enthusiasm in biology,” Pellettieri said.

He chose flatworms as a research subject because they are a workhorse of biology labs, which means they’re cheap to buy (this is a state school, after all), easy to keep alive and are well understood. They are so popular because they quickly regrow lost body parts, which is why they starred in a course titled “Regeneration.”

As part of the class, students had to design and run an experiment with flatworms.

“I give them all scalpels and pray nobody’s going to get cut,” Pellettieri said. “Most (studies) were what you might expect: How does Red Bull affect regeneration? How do energy drinks affect it, or caffeine, or alcohol? Pretty predictable.”

In 2010, one group of students wanted to study how exposure to light affects regeneration, so Pellettieri had them put a test group on a window sill (flatworms don’t like heat, so they’re usually kept away from light).

“A few days later, there was no change in regeneration but light-exposed animals had completely de-pigmented,” Pellettieri said. That is, they’d lost the color and spots associated with this species and became pure white. “They said, ‘Why did that happen?’ I said, ‘I don’t know!’ ”

“It might have stayed that way – it’s way outside my area of expertise and I thought it was real cool, but it’s not advisable with a new faculty job to chase after something that far out of your expertise,” he admitted.

Then Stubenhaus, a continuing education student who had a bachelor’s in English from elsewhere and came to Keene State for a biology degree, “knocked on my door and said he’d heard I did research and did I need volunteers.”

“He was super green in experimenting. I thought of the white worms, let him mess around with them, and when he gets more experience, I’ll move it to a real project. But he took it, ran with it, never looked back,” Pellettieri said. “It has turned into a main research project, with over half-million dollars in federal funding from (National Institutes of Health)” and other agencies.

Stubenhaus graduated and is getting a Ph.D. at Johns Hopkins University, but the lab has thrived studying ways to use flatworms to understand porphyrias, a group of rare metabolic disorders characterized by red-and-purple pigments accumulating in the body. These cause a variety of symptoms including extreme sensitivity to light, facial hair growth and hallucinations.

The lab has shown that the flatworms generate light-activated molecules called porphyrins in skin pigment cells, using the biochemical pathway involved in the human diseases. This is important because it means the cheap and easy-to-maintain flatworm might be an accurate measurement of drugs and other treatments for human disease – that is, might become animal models for the disease.

“What we stumbled on was a beautiful animal model of these rare human conditions. We’re really interested in using planarians to understand more about the basic science of the disease but in addition, I think they’ll be really useful for drug screens,” Pellettieri said. Because flatworms are aquatic, you can test a drug by putting it in their water, where they’ll absorb it. “It’s as simple as putting a drop of the compound in their tank, not like with a mouse where you have to inject them. . . . A mouse model is a lot of work and money.”

Further, it’s easy to see if a drug is affecting flatworms: just expose them to light and see what happens to the pigment. No need to shave off mouse fur.

All this has opened up multiple areas of research. “That’s the fun and frustration of science – every time you answer a question, you have 10 more to address,” Pellettieri said.

And it has produced one more effect for life in Keene, due to the fact that red LEDs have proven to be the most effective light source for testing pigmentation effects.

“We have several thousand planarians that we maintain in the lab. One whole wall is taken up with light stations. At night, if you look up from Appian Way, you see all these red lights,” Pellettieri said. “We call it Club Planaria.”

Perhaps funkiness also favors the prepared mind.

(David Brooks can be reached at 369-3313, or on Twitter @GraniteGeek.)

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