An international team of researchers including scientists from The Australian National University (ANU) have developed a way to reveal the smallest of malfunctions in the biochemical machinery that makes proteins in our bodies.

According to the researchers, these malfunctions, however small, can trigger neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, as well as cancer and developmental disorders.

The ANU researchers used a technique, which works by squeezing molecules through tiny holes in a silicon-based membrane, helps scientists understand how a mutation in a transfer RNA (tRNA) molecule – tRNA is a molecular messenger essential for building proteins – affects the molecule’s real-time structure.

tRNA is part of our genetic code. tRNA molecules help build proteins, which are essential for structure and function of our human bodies. A mutation in these molecules can disrupt the body’s protein building machinery, which can cause disease.

According to ANU Professor Patrick Kluth, the new ability to identify malfunctions in the body’s protein-developing machinery could enable a better understanding of disease pathways and ultimately lead to new and more effective treatment options.

“We are examining the machinery that builds proteins in the first place. It's like checking the assembly line rather than inspecting finished products – allowing us to catch and understand problems much earlier,” he said.

“A single letter mutation in tRNA, just one building block swapped for another, can distort its shape and disrupt protein production. This is particularly damaging in brain cells because they have exceptionally high protein synthesis demands.”

The team analysed over three million individual tRNA molecules. Using the technique they developed, the researchers compared samples of standard tRNA molecules with mutated tRNA and discovered the mutant tRNA molecules can be permanently stuck in unusual shapes, which triggers the onset of disease.

“We can directly detect and measure changes in mutant tRNA in real-time and see how they change their shape from one form to another, at scale – something which has been impossible until now,” lead author Dr Shankar Dutt said.

"For example, we discovered that the mutant tRNA adopts different shapes compared to the healthy tRNA molecules – and being able to spot molecular problems at their earliest stage is important because it helps us to understand why diseases occur in the first place.”

Dr Dutt said the technology is helping researchers understand disease mechanisms.

“More than that, the technology can be used for screening potential therapeutic drugs that stabilize the functional shapes of these tRNA. This could lead to massive advances in treatment of these diseases,” he said.

This work was led by ANU and involved scientists from the United States and Poland. The research is published in Nucleic Acids Research.