Mapping the “Social Network” of Proteins in the Cell

By Catherine Couturier Sep 25th, 2026

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In 5 seconds By studying interactions between proteins, the laboratories of Adrian Serohijos and Stephen Michnick want to understand how genetic information shapes the characteristics of living things.

Inside cells, proteins interact dynamically and form a network of interactions.
Photo : GETTY

One of biology’s fundamental questions is how our genes shape who we are. Adrian Serohijos and Stephen Michnick, professors in the Department of Biochemistry and Molecular Medicine at Université de Montréal’s Faculty of Medicine, are studying the relationship between genotype and phenotype, that is, how DNA becomes RNA, then protein, and ultimately gives rise to observable characteristics in an individual or any other living organism. “We’re trying to unravel the mechanisms of the genome, specifically how the information it encodes is processed inside the cell,” Serohijos says.

The problem can be approached in two ways: one is to look at how an organism changes when disturbed by its environment. The second, taken by researchers at the Courtois Institute of Innovation, is to focus on mutations in an individual’s genome, which play an important role in defining our individual traits. “This is an important question because our DNA determines not only our physical characteristics, such as eye color, but also how we respond to medications, which is essential in the context of personalized medicine,” Michnick explains. However, predictions cannot be made based on an individual’s DNA alone.

While DNA has long been decoded, as has RNA, Serohijos, Stephen W. Michnick and their colleagues, including Savandara Besse, then a doctoral student, and Tatsuya Sakguchi, who was a visiting professor at UdeM, have published the first study to examine the relationship between genomic mutations and the protein “social network” in the cell. Launched during the COVID-19 pandemic, the project was conducted in collaboration with the laboratory of Julie Hussin, a professor in the Department of Medicine, and is now the subject of an article in the prestigious journal Nature Genetics.

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Adrian Serohijos, professor in the Department of Biochemistry and Molecular Medicine at the University of Montreal — Adrian Serohijos, professor in the Department of Biochemistry and Molecular Medicine at Université de Montréal
Photo : Benjamin Seropian

Thinking Big at the Smallest Scale

Inside cells, proteins interact dynamically with one another, forming a network of interactions. The state of this “social network” helps define the characteristics of cells and individuals.

What if mutations in DNA caused changes in protein networks and, ultimately, in the characteristics of individuals? That is what Serohijos, Michnick and members of their laboratories set out to investigate. Their new approach examines the social network of proteins to identify the unexpected effects of mutations, some of which are associated with disease, as well as environmental perturbations, such as those caused by exposure to medications.

The researchers applied their method to 350 strains of the yeast Saccharomyces cerevisiae, a single-celled fungus, which they exposed to several drugs, including antifungals, an antidiabetic drug and an antipsychotic. Nearly 1 million protein-protein interactions were measured. “The idea is to trace the flow of information from DNA to protein and understand how proteins interact within the cell, so that we can eventually explain why mutations affect the characteristics of an individual organism,” Michnick says.

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Stephen Michnick, professor in the Department of Biochemistry and Molecular Medicine at Université de Montréal
Photo : DUCKAFTERDUCK

Network Nodes

To their surprise, the researchers found that changes in protein interactions most often came from mutations elsewhere in the genome, in genes that appeared to have no direct connection to the proteins involved. “What surprised us most is that a mutation in one gene can alter the interaction between two proteins even when that gene itself does not produce either of those proteins,” Serohijos says. Such a mutation can therefore act at a distance, much like a friend of a friend in a social network. Some of the most influential mutations are even found in noncoding regions of DNA, once referred to as “junk DNA.” These regions do not code for proteins but help regulate their production.

Not all relationships between proteins are equal, either. Some are stronger, while others are weaker. Some proteins therefore act as hubs. “The advantage is that, from a simple sample of some of these interactions, we can get an overall picture of the cell and infer how it functions as a whole,” Michnick says.

“These results offer a new roadmap for tracing how changes in DNA ripple through the cell’s social network of proteins and, ultimately, shape our traits and our health,” Serohijos says. He now wants to repeat the experiment using human cells. “This is a fundamental problem in hospitals, where clinicians want to understand why someone responds well, or not, to medications. It’s the key to personalized medicine,” he concludes.

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