Seeking One Piece of the Puzzle

Working under a grant from the National Institutes of Health, Rebecca Lyczak, a professor of biology, and her students are continuing a research project with an eye on unlocking mysteries surrounding a protein called PAM-1.

Lyczak is intimately familiar with PAM-1, a key regulator of the cytoskeleton and polarity establishment in C. elegans, a model organism.

“I’ve been working on PAM-1 since I’ve been here,” the Ursinus scientist says.

In fact, when her research began, Lyczak says the protein was an unknown.

“For a geneticist, work sometimes starts with a new mutant that affects a process of interest, so you don’t even know what gene you’re working on,” she says of taking on a research project in its infancy. “You’re working on a problem—in this case, polarity—and once you have a gene, it brings the research to a new level.”

It’s a good example of how impactful research evolves over time and the many stages of discovery on a scientist’s journey.

“We were the first ones to identify it from studying what goes wrong when it has a mutation,” she explains.

During development of diverse organisms, many cells become polarized as part of the differentiation process. Polarization is integral to the shape and functioning of individual cells and tissues, and it involves regulation of the cytoskeleton, which provides the structure of a cell.

Using C. elegans embryos, Lyczak and her students explore the role PAM-1 plays in regulating the cytoskeleton’s role in polarity and identify new genes that work with PAM-1 during this process. If there’s a mutation in pam-1, the cytoskeleton can’t organize and the embryos die.

To identify new genes, Lyczak lab members have conducted a suppressor screen, looking for pam-1 mutants that now survive. “We identify a suppressor that rescues the effect of the first mutation in pam-1,” Lyczak explains. “We screen for worms that survive because it means they have some compensating mutation that allows them to survive.”

“If this mutation can counteract the effect of the first, it must be involved in the same process,” she says. “Those are the genes we’re trying to identify.”

That could eventually play a role in better understanding—or even treating—neurodegenerative diseases such as Alzheimer’s and Huntington’s. PAM-1 is a puromycin-sensitive aminopeptidase (PSA), which are found in a large number of organisms and play important developmental roles, including a neuroprotective role in these disorders.

“Once we know what the suppressor is, we could find the human version of that gene,” Lyczak says. “It could give us a piece of the puzzle.”

This summer, two students are working with Lyczak through Ursinus’s summer fellows program and are sponsored through the NIH grant: Angela Hong ’20 and Ethan Kabel ’20, along with an Ursinus graduate, Arielle Kilner ’15, now pursuing a master’s degree at Drexel University. Eva Jaeger, an Ursinus research technician, also plays an important role in the work.

“In high school, I would hear that many institutions don’t really allow you to do a lot of research as an undergraduate, so I recognize that being able to do that here at Ursinus is really amazing,” says Kabel, who has been working in Lyczak’s lab for nearly a year.

“I got to know Dr. Lyczak through CIE and I looked up to her as a role model, especially as a woman in science,” Hong says. “It’s been a great opportunity to be able to work on a research project in her lab.”

Lyczak’s NIH grant was renewed in October 2017 and runs through 2020. The experiments are largely carried out by undergraduate students who will have opportunities to publish their work and present at national meetings. —By Ed Moorhouse