Understanding and protecting against synaptic dysfunction in disease and trauma: Blizzard Lab

Motor neuron disease (MND) and frontotemporal dementia (FTD) exist on a spectrum, where they share key pathological hallmarks, and underlying mechanisms. They are progressive neurodegenerative diseases with no cures. Over ten years ago it was discovered that MND-FTD is pathologically characterised by the aggregation of the RNA/DNA binding protein TDP-43, however this protein’s role in disease has remained unclear, which has been a barrier to treatment development. Our research has discovered that TDP-43 has a critical role in generating hyperexcitability in the brain, which is an early clinical feature of MND. We have discovered that TDP-43’s action is complex, disrupting network excitability in a compartmentalised and region-specific manner, however not too complex to overcome if treatment is similarly tailored. We are now using a multi-system approach to determine what the earliest changes in excitability in MND-FTD are, how they cause widespread neurodegeneration, and if we can target them with treatments to improve symptoms.

Over 60 million new cases of traumatic brain injury (TBI) are diagnosed worldwide each year and it is a leading cause of death and disability for persons under the age of 45. A greater understanding of TBI and effective interventions are urgently needed to combat the complex sequalae of degenerative events that occur following an injury. Understanding the organisation, structure and cellular mechanisms that underpin the complexity of the human brain remains one of the biggest challenges of science, and an incomplete comprehension of the short and long-term consequence of TBI and the contribution of risk factors such as region of insult, age and sex is an immense barrier to the development of effective therapeutics. Our program of research embraces the complexity of the brain and heterogenous nature of TBI to unravel the ambiguity surrounding how the brain responds to TBI and provide a platform for trialing therapeutic interventions.

We use mouse models, cell culture systems, in vivo live imaging, electrophysiology and biochemical techniques to ask our research questions. We have numerous national and international collaborators. We are currently recruiting motivated honours and PhD students, please contact Cathy (Catherine.Blizzard@utas.edu.au) for more information.

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  • Dr Catherine Blizzard
  • MS Grace Barnett (Research Technician)
  • Mr Marcus Dyer (PhD student)
  • Ms Laura Reale (PhD student)