A nearly three-decade-old scientific puzzle has finally been solved, thanks to an unusual collaboration that began with a conversation at a conference. The findings, just published in the journal Cell Reports, reveal the discovery of a long-sought gene responsible for a crucial type of methylation, a key biochemical process that influences how cells function.

Researchers have finally identified this gene as SMYD5, and it plays an essential role in protein translation. The breakthrough was made possible when a University of Melbourne scientist who had been holding onto a critical biochemical sample for years shared it with a colleague at UNSW who had the right tools to solve the mystery.

A Missing Piece of the Puzzle

For years, scientists knew that this particular methylation existed, but they had no idea which gene, or enzyme, was responsible for it. The breakthrough came when Melbourne Associate Professor Nicholas Williamson, who had first discovered this methylation in the late 1990s, approached UNSW-MACSYS scientist Dr. Joshua Hamey at a conference with an offer. Williamson had stored a biochemical asset in his freezer for decades, hoping someday it could unlock the puzzle. He sent it to Hamey and his team at UNSW, who, using advanced protein analysis tools and biochemical assays, were finally able to identify SMYD5 as the missing link.

“This project started during my PhD.” says Dr Williamson, “I kept the reagent in the freezer because I hoped to return to it at some point in the future. Over 25 years passed before I came across Josh’s work and realised he could complete the project.”  (see feature image: sample is dated 3-7-98)

A Surprising Discovery

Methylation, the process where a small chemical tag (a methyl group) is added to molecules, is fundamental to how cells regulate growth, development, and even disease processes.

The newly identified SMYD5 gene plays a critical role in optimising protein translation, the process by which ribosomes turn genetic instructions (mRNA) into proteins. Understanding this process is essential because proteins drive nearly every biological function in the body, from muscle development to immune responses.

Hamey says this latest discovery is not just about identifying a single gene – it’s about understanding how genes shape the traits of organisms. This is known as genotype to phenotype mapping.

“Knowing what genes do at a molecular level is crucial for fields like genetic research, biotechnology, and medicine,” says Dr. Hamey.

A Step Toward Bigger Breakthroughs

Hamey is a Senior Postdoctoral Research Fellow and an Associate Investigator for the ARC Centre for the Mathematical Analysis of Cellular Systems (MACSYS). One of the aims of MACSYS is to work towards modelling a whole cell.

“Methylation is at the core of how cells function,” Dr. Hamey explained. “You can’t model an entire cell without understanding how it makes proteins. Ribosomes—the cellular machines responsible for protein synthesis—depend on these modifications to work properly.”

By identifying the molecular role of this gene, MACSYS researchers take another step forward in their efforts to model a whole cell, bringing us one step closer to fully mapping how life’s molecular machinery operates.