Dr Brent Neumann obtained his BSc (Honours) at the University of South Australia and completed his PhD in Prof Tom Gonda's lab at The University Of Queensland's Diamantina Institute. In 2008 he joined A/Prof Massimo Hilliard's lab at the Queensland Brain Institute studying the mechanisms of degeneration and regeneration in the nervous system. In 2015 Brent established the Nervous System Development and Repair laboratory within the Department of Anatomy and Developmental Biology at Monash University.

Injuries to the nervous system can cause lifelong disabilities due to ineffective repair. Understanding the basic molecular mechanisms regulating axonal regeneration is therefore essential for the development of effective therapies. As a postdoctoral fellow with Massimo Hilliard, Brent identified a mechanism of repair known as axonal fusion in the nematode Caenorhabditis elegans (Dev Dyn 2011). This highly efficient means of nervous system repair occurs such that severed axons spontaneously repair themselves by regrowing, reconnecting and fusing with their separated counterparts.

Through a detailed molecular characterisation of the process, Brent discovered that regenerative axonal fusion shares much of its molecular machinery with the process of apoptosis (Nature 2015). Following injury, the composition of the axonal membrane is altered, such that the phospholipid phosphatidylserine is exposed on the external surface to serve as a recognition, or 'save-me' signal for the regrowing axon. This 'save-me' signal is recognized by secreted ligands and receptors on the regrowing axon to allow recognition between the two axon segments. Understanding precisely how axonal fusion occurs in the nematode may allow it to be applied to other organisms and potentially allow similar mechanisms of nervous system repair to be induced in a clinical setting.

Brent's research also focuses on axonal degeneration, which can occur as a result of nerve injury or through the disruption of neuronal maintenance mechanisms, and is a common hallmark among many neurodegenerative disorders including motor neurone, Alzheimer's, and Charcot-Marie-Tooth (CMT) diseases. We lack a complete understanding of the mechanisms employed by neurons to preserve their axons over a lifetime, which has hampered the development of effective therapies.

From a genetic screening method aimed at identifying molecules that cause axonal degeneration when they become inactive through genetic mutations, Brent found that mutation of the and alpha-tubulin acetyltransferase protein, MEC-17/ATAT1 led to spontaneous, adult onset and progressive axonal degeneration (Cell Rep 2014). MEC-17 is highly conserved across species and normally protects against degeneration by stabilising the cytoskeletal structure. Brent's laboratory in the Department of Anatomy and Developmental Biology aims to identify and characterise additional cellular mechanisms necessary for the maintenance of axonal structure, and also uses C. elegans to model CMT, the most common inherited disorder of the peripheral nervous system. By modelling the disease in C. elegans, novel information about how the disease develops can be identified, and a better understanding of the disease provided to offer valuable insight for the future generation of therapeutics.

Nervous system development and repair:

• Cellular and molecular mechanisms of axonal regeneration
• Molecular mechanisms of Charcot-Marie-Tooth disease
• Maintenance of nervous system structure over time