NHMRC support for projects to drive research into brain injury, cleft palate and heart regeneration

Over 3.3 million of new Australian Government funding through the Ideas Grants scheme will support three of ARMI’s research projects into:

–   Novel mechanisms underlying craniofacial abnormalities,

–   Unlocking the hearts dormant potential to regenerate after injury

–   A new model to study how cerebral spinal fluid can help repair the brain and spinal cord

In utero correction of craniofacial malformation

Professor Edwina McGlinn will lead a team of researchers to understand the molecular drivers of craniofacial malformations.

“Craniofacial abnormalities, like cleft palate, occur in 1/700 births.” “Despite its prevalence, surgery is currently the only treatment as the underlying causes are still not well understood.” said Professor McGlinn

Professor McGlinn’s team have set out to unpick the complex genetic and environmental interactions that underlie these abnormalities, with a focus on retinoic acid signaling pathway – a byproduct of dietary vitamin A.

“Vitamin A deficiency, and changes to the retinoic pathway have been previously shown to lead to craniofacial malformation. Our team have found a genetic controller of this pathway which now enables us to investigate how to target this molecular switch and restore function”.  

The funding support has come at a critical time enabling the team, including Professor Cox, Professor Trainor and Dr Manent, to investigate how to target this pathway therapeutically using chemical inhibitors.

“Our ultimate goal is to develop a non-surgical in utero correction strategy. For this we need a deep understanding of the molecular drivers of craniofacial malformation, and those that are therapeutically targetable.”

Regrow with the flow.

A/Professor Jan Kaslin will lead a team of researchers to understand how the flow of cerebral spinal fluid is altered after brain and spinal cord injury and how to harness its regenerative potential.

The flow of cerebrospinal fluid (CSF) normally contains factors important for upkeep and health, and after injury both the circulation and composition of the CSF is altered. While sampling CSF has been routine to identify biomarkers – signals to give us a read out of brain and spinal health, less is known about how CSF circulation is controlled after this event.

“Brain and spinal cord injuries are devastating events that have a life-long impact”. “We have set out to identify how signals released after injury can be harnessed to boost the brain and spinal cords’ regenerative capacity.” said A/Professor Kaslin.

A/Professor Kaslin and his team have developed a preclinical model to study CSF flow in real-time and have discovered that damage-induced inflammatory and growth signals can alter circulation and tissue repair.

“Interestingly components of our nervous system, glia and neurons – can act as sensor and can detect changes in CSF flow and flow sensing is required for repair.”

With this new support, the team including Dr Arumugam and Dr Crossman plan to develop new imaging and computational methods to image and visualise CSF flow and repair. They hope to identify new mechanisms to help promote regeneration in the brain and spinal cord.

Exploring the proliferation potential of trabecular myocardium.

Dr Gonzalo del Monte Nieto will lead research into unlocking the dormant potential of a specific type of heart muscle involved in early heart development.

“Heart attacks often lead to massive death of cardiac muscle cells – or myocytes – and currently there is no effective way to help them regenerate.” “Everything we’ve tried so far has failed. Tissue engineering approaches result in cells that don’t couple with local cells and generate arrythmias.” Said Dr del Monte Nieto.

Dr del Monte Nieto’s team have found an innovative way to reimagine heart regeneration, by turning to early heart development.

Trabecular myocardium plays a critical role in early heart formation before the embryonic heart acquires its adult form. This specific heart muscle gives the early heart a functional advantage  increasing its pumping efficiency and helping the cardiac muscle to be properly oxygenated. While trabecular cardiomyocytes are thought to be dormant in adulthood, some evidence has shown that they can respond during a heart attack, and also play an important role in giving elite athletes a cardiovascular advantage.

The team will deep dive into how trabecular myocardium develops to understand how to bring this super heart muscle to life again in adulthood.

“We have found a gene that is specific to trabecular myocardium and switches on before the tubular structure of the early heart forms. We now have a marker that enables us to interrogate the whole developmental process and help us to find molecular targets that can be harnessed to trigger this muscle type to act following injury.”

This new funding brings together a team of researchers in Australia, including ARMI’s Dr Tran and A/Professor Smith (Uni of Melbourne), who hope to develop a targeted therapeutic approach to harness the heart’s endogenous regeneration potential.