When Phillip Newmark was choosing the direction of his postdoctoral research, he decided to study an organism that had been effectively retired from modern science. Newmark was interested in the problem of regeneration so he decided to learn all he could about a creature that had fallen out of favor since its peak of popularity in the 1960s: the freshwater planarian.
"I was fascinated by the problem of regeneration and I remembered being amazed by planarians back in freshman biology," says Newmark, who is now at the University of Illinois at Urbana-Champaign. Planarians possess what Newmark calls a "stunning ability" to regenerate. Slice one planarian into 10 pieces and 10 new planarians will grow—new brain, new reproductive organs, new everything.
After receiving his Ph.D. in molecular, cellular, and developmental biology at the University of Colorado at Boulder, Newmark sought out a lab that was investigating planarians; in 1995, he traveled to the University of Barcelona as a Damon Runyon Fellow to study with Jaume Baguñà, whose lab was one of the few in the world with expertise in planarian biology.
Newmark returned to the United States in 1997—carrying a thermos full of the creatures—and continued his postdoctoral research at the Carnegie Institution of Washington in the lab of Alejandro Sánchez Alvarado, now an HHMI investigator at the University of Utah. His thermos carried a supply of Schmidtea mediterranea, a flatworm from Barcelona that Newmark chose to work on because it has a smaller genome than most North American species and, he notes, "other good features for doing molecular biology." Furthermore, it has two genetically distinct strains: an asexual strain that reproduces by fission and a hermaphroditic strain that reproduces sexually.
Newmark has been instrumental in establishing planarians as a model system for studying regeneration at the molecular level. His work with Sánchez Alvarado at Carnegie applied modern cellular and molecular biological tools to the study of planarians. In 1999, they showed that RNA interference could inhibit gene expression in planarians. In 2000, they devised a way to fluorescently label planarian stem cells. And so began the functional analysis of planarian genes involved in regeneration.
S. mediterranea's capacity for regeneration is driven by a stem cell population that is maintained throughout the animal's life. The stem cells differentiate to become any of the animal's cell types, among them the germ cells, the precursors of egg and sperm, that give rise to the next generation of animals. Newmark finds germ cells fascinating because they are highly differentiated, yet they maintain their totipotency—the ability to divide and produce all the cells in an organism.
Newmark is exploring a central question that has long intrigued biologists—what are the signals or cues that tell a cell to become a germ cell? He hopes to answer that question by studying the ways planarians develop and regenerate their germ cells. "It is well known that you can cut their heads off and they'll grow back brains. That's obviously interesting and it is something that we are studying. But it is underappreciated that planarians can make their germ cells de novo from their stem cells," he says. The way they make those germ cells appears to be similar to the way mammals make their germ cells. Ongoing molecular investigations in Newmark's lab hold the promise of defining what makes a germ cell a germ cell and whether the signaling that triggers germ cell development has been conserved across species.
The gamble to resurrect a neglected animal model more than a decade ago has revitalized interest in a long-standing problem of developmental biology. "I wanted to study something that would keep me absolutely engaged for the rest of my career," he says. "To pick a big problem where I could make a real contribution."