RNA chaperoning earns alumnus science accolades

By Steve Seepersaud

Daniel Herschlag ’82 is thankful for his Binghamton University mentors. He fondly recalls taking a biochemistry course taught by Fred Kull and working in Gene Stevens’ chemistry lab.

“Having this support was critical because I came from a small town, didn’t have much confidence — and no one in my family had graduated from college,” Herschlag said. 

As an academic for more than 30 years, Herschlag is most proud of giving aspiring scientists the same level of mentoring and helping produce the next generation of researchers.

Herschlag is professor of biochemistry at Stanford University, where he serves as principal investigator of the Herschlag Lab, which explores how enzymes work, how ribonucleic acid (RNA) folds, how proteins recognize RNA, RNA/protein interactions and the evolution of molecules and molecular interactions.

"We look to uncover principles in biology that represent truths in nature,” Herschlag said. “The foundations of our work are physics, chemistry and evolution — because physics and chemistry define and describe how all the molecules which make us behave, and because those molecules have arisen through probabilistic pathways of evolution."

Later this month, Herschlag will receive the Biophysical Society’s 2020 Founders Award for his contributions to research in RNA folding and enzymology. He was inducted into the National Academy of Sciences last spring.

"My research has never fit into any single area, so to have [the Biophysical Society] recognize our work is especially meaningful,” Herschlag said. “But what’s most meaningful is that other scientists took the time and made the effort to support me and my lab’s research through this nomination."

In particular, Herschlag and his team have made breakthroughs in what they call catalytic promiscuity and RNA chaperones. Look beyond the playful names and you’ll see serious things happening.

Catalytic promiscuity builds on the basic question of how new enzymes arise in evolution. Herschlag said there is good evidence the first step is gene duplication, because that allows one copy to keep functioning and the other to explore new opportunities. However, if the duplicated gene product already had some very low level of activity for the newly desired reaction, its optimization could be guided by natural selection. He said this is very common and likely inherent to evolution. 

Herschlag said the idea of RNA chaperones came from realizing that most RNA molecules, left on their own, fold into structures too stable to respond in a timely manner to biological stimuli. He showed that small proteins that bind RNA can help RNA rearrange and thereby overcome this limitation.

“We speculate that RNA chaperones were critical in the transition from an ancient ‘RNA World’, where RNA played roles as genetic and functional material, to the current biological world dominated by proteins for function and DNA (and RNA) for storing and transmitting genetic information,” Herschlag said.

Herschlag said Binghamton nurtured his love of science and provided opportunities to explore interests in other areas. This is key to the work he does now that transcends traditional boundaries.

"[Our research] exemplifies how bringing together thinking across evolution and chemistry and physics can lead to new insights," he said. “I loved Binghamton for many things. Most of all it was small enough that I could be a biochemistry major yet still write for the Pipe Dream and co-edit the campus literary magazine. I think a breath of experience is great preparation for doing things that are new and different, and Binghamton was at the heart of this for me."