From left: He Leng, Mikko Taipale and Guillaume Dugied

31 August 2026

By Aideen Teeling

EPIC researchers at the University of Toronto, working with colleagues in Austria, developed a scalable system to decode how proteins from viruses, bacteria and parasites disrupt cellular processes to cause illness.  

Pathogens — bacteria, viruses, fungi, and parasites that cause disease — infect our cells using an arsenal of weapons called effector proteins. Unlike surface proteins, which help pathogens break into cells, effector proteins suppress the cell’s protective responses, helping the pathogen survive, replicate, and evade detection so it can spread to other cells.  

Effector proteins have been deeply studied in some of the world’s most consequential pathogens, like HIV, influenza A, and SARS-CoV-2, but this “one at a time” approach has left a scattered, slow-moving picture of how effector proteins work.  

Mikko Taipale, an EPIC researcher and principal investigator at U of T’s Donnelly Centre for Cellular and Biomolecular Research, set out to change this.  

Published in August 2026 in Cell, the Taipale Lab demonstrated a new high-throughput approach to characterizing effector proteins from many different pathogens at once. Rather than characterizing the role of individual proteins in a specific pathogen, the researchers focused on how effector proteins from different pathogens impact common cellular defense pathways.  

Taipale teamed up with Alexander Stark, a colleague from his graduate studies who is currently a senior scientist at the Research Institute of Molecular Pathology at the Vienna Biocenter and adjunct professor at the Medical University of Vienna. Together, they developed a technique to simultaneously measure how thousands of pathogen effector proteins affect fundamental, well-understood cellular defense pathways.  

By observing which effector proteins enhanced or inhibited each pathway, the researchers pinpointed what each protein does and how it hijacks human proteins to override the cell’s defenses. The information uncovered from these observations could support new treatment development to target many different pathogens through common cell pathways.  

To begin characterizing effector proteins, co-first authors Tomas Pachano in Austria and He Leng at the Donnelly Centre worked together to create a library of approximately 4,000 DNA sequences that encoded effector proteins, also known as effector open reading frames (eORFs), from 250 different pathogens that infect humans. The eORF library, or eORFeome — a term coined by the researchers — served as a proof-of-concept to show that characterizing many different proteins at once by observing their effects on essential cellular pathways would yield a better understanding of how pathogen effector proteins inflict damage. 

Guillaume Dugied is a postdoctoral researcher in the Taipale Lab and second author of the publication. He explains how this approach is rooted in systems virology, where computational biology meets infection models in the lab. Dugied compares the approach to a familiar system: 

“It’s just like a library where you would go to borrow a book,” Dugied explains, who is also a 2024 EPIC Convergence Postdoctoral Fellowship recipient. “We put thousands of books in one small tube.”  

Dugied further describes how when each book is read by a cell, it leads to the expression of the effector protein in the absence of a real infection. So, Taipale and his team were able to study each protein’s role in isolation without the difficulties of infecting human cells in the lab with each of the 250 pathogens, which would otherwise be slow and technically challenging. 

“The most exciting part is that we started with absolutely nothing and built the whole thing ourselves, piece by piece,” says Leng, a previous postdoctoral researcher in the Taipale Lab who led this project.  

To build this library, the researchers turned to colleagues specializing in specific pathogens and asked them to share DNA sequences of effector proteins, some with known functions and others with no recorded function. EPIC collaborators John Brumell, Rob Kozak and Alexander Ensminger provided effector protein sequences for Salmonella, mpox virus and Legionella pneumophilia, respectively. 

Once researchers encoded the effector proteins with the eORF library and expressed the proteins in human cells, they artificially induced different cellular pathways involved in eliminating infection. Then, they sorted the cells by whether the pathways were enhanced or inhibited. Gene sequencing was used to identify the eORFs that elicited the effect in individual cells.  

“[The system] gives you a single cell look at what is happening,” says Dugied, who is also co-chair of the EPIC Trainee Advisory Committee. 

The researchers identified hundreds of effector proteins that manipulate key cellular defense mechanisms, confirming some known protein functions, revealing new ones for already-studied proteins, and discovering functions for proteins that had none on record.  

The research team detailed new functions for four proteins. One of the most significant findings involved a group of adenovirus (hAdV) effector proteins, called 13.6K, that block TAP (Transporter associated with Antigen Processing) – a channel that delivers protein fragments (antigens) to MHC-I (major histocompatibility complex class I) which go to the cell surface and alert the immune system that the cell is infected. By blocking TAP, 13.6K adenovirus proteins help infected cells stay hidden from the immune system.  

In contrast, the effector protein U21 in human herpes viruses (HHV) was previously known to inhibit MHC-I. However, in this study, a different part of HHV-U21 was also found to interfere with intracellular mechanisms to recognize foreign DNA, helping the virus remain undetected in the cell. This was an unexpected finding and is the first time that dual function has been identified for U21, explains Leng, and demonstrates how a single effector protein can suppress immune responses in multiple ways.  

For many effector proteins in the eORFeome, functions had never been characterized. But the researchers knew testing these proteins would yield some insights because many other effector proteins targeted these common pathways. 

The researchers are now expanding the library to include upwards of 20,000 eORFs, characterizing the weapons pathogens use to gain a foothold for infection. They also hope that other research groups will build on their eORFeome library system to make similar discoveries in other pathogens and expand the system to include other cellular pathways.  

“Our eORFeome platform is currently one of the largest-scale pathogen resources for functional screening,” says Leng. “It provides a new paradigm for protein function discovery.” 

For Taipale, the project also underscored something bigger: how effector protein genes across unrelated pathogens keep evolving toward the same targets. “Viruses and bacteria just do things in a creative manner,” he says.  

“It’s really a testament to the power of evolution and the host-pathogen arms race.”