Alum Profile: Exploring Nature's Way to a Healthier Planet
Inspired by her engineer father, teacher mother and environmental scientist aunt, Amy Fraley has charted a unique career path to the juncture of natural product chemistry, pharmaceutical sciences and environmental sustainability, with a core focus on educating the next generation of scientists.
Fraley is an assistant professor of medicinal chemistry at ETH Zürich, the Swiss Federal Institute of Technology and one of the top universities in continental Europe. At ETH, she leads a research group centered on bioactive natural products — generating enzymes and synthetic biology platforms that can be used to develop new medicines and better understand disease mechanisms. (Think of the powerful cancer drug paclitaxel, for example, bioengineered from yew trees.) The lab is also interested in how the natural defenses in plants and invertebrates could be harnessed to address the health of our planet.
This focus carries into the classroom, too, where Fraley teaches pharmaceutical biology with an emphasis on natural products derived from plants. Bioactive extracts and supplements are widely sold in pharmacies in Switzerland; she trains pharmacy students in the science of distinguishing fact from fiction regarding bioactive molecules in these preparations.
For Fraley, it all started with marine sponges.
This was really a pivotal point in my career. I realized after this experience in David’s lab that this was the direction I wanted to go with my career and I, too, had the potential to obtain a doctorate in this field.
As an undergraduate studying marine biology at Millersville University of Pennsylvania, she was fascinated by a section in her organic chemistry textbook about anti-cancer molecules isolated from sponges. The realization that complex chemistry occurs in natural systems spurred her decision to change her academic major and move to the Department of Chemistry.
In 2013 she made her way to the University of Michigan’s Life Sciences Institute for a 10-week summer study program in the lab of chemist David Sherman, whose research focuses on the biosynthesis of natural products from microbes from both marine and terrestrial organisms.
“This was really a pivotal point in my career,” Fraley recalls. “I realized after this experience in David’s lab that this was the direction I wanted to go with my career and I, too, had the potential to obtain a doctorate in this field.”
After completing her bachelor’s degree in chemistry, she returned to U-M to pursue her Ph.D. in pharmacy, again joining the Sherman lab and adding LSI faculty member Janet Smith as a co-mentor. Fraley says co-mentoring made perfect sense for pursuing her academic interests.
“I could do the whole span of natural products research in their groups, both of them in the LSI, one floor apart,” she explains. “It exemplified the kind of collaboration that’s fostered in the LSI.”
When it came time to begin her postdoctoral research, Fraley’s initial fascination with sponges lured her to work in the lab of Jörn Piel at ETH Zürich.
Piel had discovered that, many times, it’s not the sponge that makes the anti-cancer molecules — it’s actually a microbe living inside it, Fraley says. In the Piel lab she studied Mycale hentscheli, a marine sponge species known to be a prolific source of anti-cancer polyketides.
“For a while it’s been unknown how these compounds were made. I’m figuring that out, what organism is making them and how they do it,” Fraley says. “The final results aren’t published yet, but it’s an exciting story.”
Fraley saw the potential of natural product biochemistry to facilitate production of molecules with the potential to improve both human and environmental health
Fraley finished her postdoctoral fellowship in December 2023. During her time abroad, she found she really liked Switzerland and the excellence of research at ETH, she says. She landed her tenure-track position at ETH Zürich in January 2024 and launched her research program. Now the group is combining synthetic chemistry with biochemistry to produce complex molecules that can be used to understand disease mechanisms in humans and plants.
One challenge for the field, she says, is the sustainable production of natural products — not over-farming plants and sponges with bioactive properties. To that end, one of the first projects in her group involves the laboratory cultivation of bioactive Swiss alpine plants.
“That brings us to the next challenge, which is using our knowledge in natural product chemistry and medicinal chemistry to give back to nature,” Fraley says. “Instead of just taking from nature to develop medicines, how can we use similar methodologies to ultimately protect biodiversity? With our laboratory cultures, we are generating microcosms, studying their metabolic reactions to environmental changes and ultimately using these data to understand the resilience of protected plants under climate change conditions.
“It’s caring for the planet and caring for human health at the same time.”