New insight into nerve protection and repair
Professor Massimo Hilliard’s lab has spent more than two decades tackling a deceptively simple question: how do neurons stay intact and what happens when they don’t?
It’s a question that sits at the heart of some of the biggest challenges in neuroscience. Damage to neurons, particularly their long, cable-like extensions known as axons, underpins everything from traumatic injury to neurodegenerative disease.
“The moment you break an axon, communication is lost. But if we understand how to repair it, we may be able to restore those connections.”
A lab built on regeneration
Since setting up his lab at Queensland Brain Institute in 2007, Professor Hilliard’s work has centred around the microscopic roundworm Caenorhabditis elegans (C. elegans). Despite having only 302 neurons, it shares many key biological mechanisms with humans and allows researchers to observe and manipulate individual nerve cells in living organisms.
Using this model, Professor Hilliard’s team has been able to slice the axon of a single neuron to see how C. elegans repair it. One of their most notable discoveries is that some damaged axons can fuse back together. Rather than regrowing entirely, the severed ends reconnect, restoring function in a process known as axonal fusion.
“It’s a very efficient process,” said Professor Hilliard, who received his PhD in Biological Chemistry and Molecular Biology from the University of Naples, Italy in 2001.
“Instead of an injured axon having to regrow its entire length to reconnect with its original target, whether another neuron or a muscle cell, it can regrow until it reconnects with its own separated fragment, restoring the neuron's function.”
Nerves are made of dozens of axons, and this discovery challenged long-standing assumptions about nerve repair and opened new avenues for treating injury. The lab later identified key molecules involved in the fusion process, including proteins that act as a kind of molecular glue without which animals cannot repair their nerves.
Seeing nerves in action
The lab’s ability to observe nerve cells in real time is central to its success. By combining genetic manipulation with high-resolution imaging, researchers can track individual axons as they break, grow and repair themselves.
This approach allows the team to study processes at the nanoscale, capturing how molecular structures organise during injury and recovery. It also enables precise experiments, such as severing a single axon and following its fate, which is difficult or impossible to track in more complex animal systems.
Looking beyond the neuron
A key theme in the lab’s work is the idea that neurons cannot be understood in isolation. While traditional neuroscience has focused on processes within neurons, the Hilliard lab has highlighted the importance of surrounding tissues in maintaining neuronal structure and function.
In a recent study with Dr Sean Coakley from UQ’s School of Biomedical Sciences, the team identified a nanoscale scaffold present in the skin that acts like a protective “cast” around the axons of sensory neurons. Using advanced genetic tools and super-resolution imaging, they discovered a lattice-like structure formed by spectrin proteins that reinforces axons externally.
“What we’ve shown is that neurons don’t just rely on internal support, they also depend on the tissues around them."
This work builds on years of research showing that axon health relies on a dynamic partnership between neurons and their environment, an idea that is reshaping understanding of the nervous system.
New treatments
Although the research is grounded in basic science, its implications extend to human health. Axon damage is a hallmark of conditions such as Alzheimer’s disease, Parkinson’s disease and spinal cord injury. The ability to reconnect nerve cells following an injury is a huge goal in science.
Collectively the Hilliard lab’s work is helping to redefine what is possible in nerve repair. By uncovering both the intrinsic resilience of neurons and the critical role of their surrounding environment, the team is laying the groundwork for therapies that actively restore connections.
While significant challenges remain, these insights offer a compelling glimpse of a future where the loss of neural function may no longer be permanent, but something that can be repaired, rebuilt and, ultimately, reversed.
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