U of T Scientists Discover Protein-Driven Inheritance in Worms, Landing the Cover of Nature Cell Biology

U of T Scientists Discover Protein-Driven Inheritance in Worms, Landing the Cover of Nature Cell Biology

Researchers from the University of Toronto's Department of Molecular Genetics have discovered a new inheritance mechanism in the worm species C. elegans, earning them the cover of Nature’s Cell Biology Journal.

Professor Brent Derry from the Department of Molecular Genetics in Temerty Medicine, then-PhD trainee Matthew Eroglu (currently a Postdoctoral Research Scientist at Columbia University), and their team aimed to study cancer signalling pathways. Surprisingly, they found a pattern in some of the worms they used for their research: they became less fertile and more feminine as generations passed.

This observation led the team beyond traditional genetics to the field of epigenetics. Eroglu, first author of the paper, reflected, “We started with a different focus... only to find that some worms were becoming less fertile over time.”

Amyloids: Protein Structure Influencing Inheritable Traits

Eroglu’s curiosity led to the discovery that amyloids—proteins typically linked to neurodegenerative diseases like Alzheimer’s— influence inherited traits.

Further investigation revealed intriguing structures within the germlines of worms (the cells that produce eggs and sperm). Eroglu described these structures, which they named herasomes, as "glowing blobs" due to their autofluorescent properties. A closer examination confirmed that these herasomes are aggregates of amyloid proteins.

These herasomes accumulate when the genes mstr-1 and mstr-2 are mutated, which disrupts normal sex determination and results in more feminized offspring. In other words, a worm that would have developed male traits in their germlines instead develops female traits. Remarkably, these amyloids pass traits to future generations without changing DNA.

Why It Matters: A New Mechanism for Epigenetic Inheritance

Traditionally, epigenetic inheritance — where traits are passed down without direct DNA changes — has been attributed to small RNAs or modifications to chromatin. However, this discovery suggests that proteins, specifically amyloids, can also transmit heritable information, which Dr. Brent Derry, Eroglu’s supervisor, calls protein-based epigenetic inheritance.

Unlike other epigenetic factors, amyloid-based inheritance seems to transfer protein states directly. It affects development in a way not seen in genetic research.

According to Dr. Derry, he adds: “Matthew really opened up about a new form of epigenetic inheritance. He found that amyloids can be inherited, marking a significant discovery in protein-based epigenetic inheritance. This changes the way we think about this field entirely.

The Worm Pic That Made the Cover of Nature Cell Biology

Eroglu’s amyloid inheritance discovery didn’t just surprise his laboratory team—it also earned him the cover of Nature Cell Biology, one of the most prestigious scientific journals in the field. And the image on the cover? The very one he set as his phone background years ago.

“I actually took that picture on the confocal scope in 2019 or 2020,” Eroglu says. “I’ve had it as my phone’s background ever since.”

The picture shows a worm right at the moment when its reproductive system is switching from making sperm to making eggs — a perfect metaphor for Eroglu’s discovery. While researching for one thing, he discovered another.

Implications for Human Health

While this research focuses on worms, it hints at broader implications for human health, especially in conditions like Alzheimer’s, where amyloid buildup is significant. This discovery could impact future research on heritable diseases and trait inheritance if similar mechanisms are at play in humans.

The findings suggest a new layer of inheritance that may help explain cases where traits are passed down without clear genetic causes, a problem known as “missing heritability.”

Eroglu explains: "There are a lot of traits and disorders that we know are passed on from parents to offspring if we look at family trees and so on, but when people have done genome-wide association studies trying to link these traits to mutations or variants in genes, they frequently fall short of explaining all of the heritability that we see.”

This discovery also opens new possibilities for understanding how certain traits or diseases could be inherited in humans.  Eroglu adds: “What could be one implication for my work is that perhaps this is why [we see missing heritability]. There's this alternate inheritance mechanism on top of DNA.” He then adds: “Who knows what you could do? Could we discover something that, in fact, doesn't change sex but changes some other traits? Or predict diseases that we couldn’t base on DNA alone?”

Final Thoughts

Eroglu’s discovery is poised to transform future research, offering a fresh perspective on inheritance and broadening the DNA-centric view of trait transmission. Scientists have been trying to figure out why some traits and diseases run in families without clear genetic explanations, and Eroglu’s work may just hold the answer.

Article updated on previous post on Nov 1: 

Research on Heritable Amyloids from Brent Derry's Lab Featured on the Cover of Nature Cell Biology

University of Toronto researchers, under the guidance of Professor Brent Derry, have identified a novel inheritance mechanism involving amyloid proteins in worms, challenging the conventional DNA-focused perspective on genetic transmission. Led by PhD graduate Dr. Matthew Eroglu, the study found that these proteins can carry traits across generations. This discovery has the potential to transform our understanding of genetics and carries important implications for human health.