Digitally created image of brain in skull

ForeFront

RESEARCH CENTRE

Our 5-year-plan

In five years we aim to have a number of novel models and target molecules for high-throughput intervention studies, and developed better diagnostic tools for identifying and tracking the underlying proteinopathy.

Our 5 year planYear 1 Aims
Clinics

Neuroimaging (Hodges) – establish the neural basis of on disinhibition, neuroendocrine changes and memory changes using cognitive and imaging approaches.
Electrophysiological tracking (Kiernan) – looking at the incidence, pattern, severity and functional significance of motor system involvement in FTD.
Neuropathology

Retrospective clinical analyses (Halliday and Hodges) – Postmortem cases will be stratified according to clinical syndromes.
Retrospective pathological analyses (Kril) – identify features predictive of the underlying pathology.
Biology

Molecular mechanisms of toxicity (Ittner) – determine the contribution to cell death induced by different species and mutant forms of tau, TDP43 and FUS.
Identifying genes that confer protection (Götz) – identify protective genes, and to determine which genes discriminate vulnerable from protected neurons.

 

Year 2 Aims
Clinics

Neuroimaging/connectomics (Hodges) – Progression in vivo of specific patterns of degeneration at different disease stages.
Electrophysiological tracking (Kiernan) – bvFTD will be longitudinally assessed using TMS.
Pathology

Quantifying degeneration in patients (Kril) – Tissue atrophy, type and severity of neuronal loss and inclusions.
Changes in protein levels as a read-out of disease progression (Halliday) – across different brain regions to determine the pattern of disease progression, and rate of change over the course of disease.
Candidate diagnostic approach (Halliday) – assess serum levels of the main pathogenic proteins involved in FTD/MND.
Biology

Changes in protein levels as a read-out of disease progression (Ittner) – vin multiple brain regions using tissue from validated animal models of progression.
Cell culture models of disease spreading (Ittner) – will identify the distinct tau protein species and mechanisms that promote spreading of pathology.
Forward genetics to identify disease modifiers (Götz) – use genome-wide ENU mutagenesis and mapping to reveal molecules that regulate neurodegeneration.

 

Year 3 Aims
Clinics

Neuroimaging (Hodges) – assess neural basis of more deficits using cognitive and imaging approaches.
Electrophysiological tracking (Kiernan) – The incidence, pattern, severity and functional significance of motor system involvement continued.
Clinical trial (Hodges and Kiernan) – develop the biomarker tool and collect baseline data for monitoring any change over the course of disease.
Neuropathology

Retrospective clinical analyses (Halliday and Hodges) – Postmortem cases will be stratified by pathology.
Retrospective pathological analyses (Kril) – identify features predictive of the underlying pathology.
Quantifying degeneration (Kril) – validate the rate of change in different brain regions to compare with animal models of progression.
Changes in tau protein levels (Halliday) – using fresh tissue from autopsy-confirmed patients to validate animal models of progression.
Validation in human tissues (Kril and Halliday) – assess genes that confer protection in animal models.
Biology

In vivo mouse models (Ittner) – develop novel in vivo models of pathological spreading along neuronal networks.
Cell culture models of disease spreading (Ittner) – identify the distinct TDP43 protein species and mechanisms that promote spreading of pathology.
The worm C. elegans as model system (Götz) – assess the integrity of neurons expressing abnormal protein inclusions.
Novel transgenic mouse models (Götz) – The mice will be analysed for phenotypic alterations, biochemically, behaviourallyand histologically.

Year 4/5 Aims
Clinics

Neuroimaging/connectomics (Hodges).
Motor as biomarker (Kiernan and Halliday).
Electrophysiological tracking (Kiernan).
Symptom management (Hodges and Kiernan).
Neuropathology

Quantifying degeneration (Kil).
Changes in tau protein levels (Halliday).
Candidate progression approach (Halliday).
Biology

Neuroprotection in C. elegans (Götz).
Validation of neuroprotective genes in mice (Götz).
Novel transgenic mouse models (Götz).
Clearing protein aggregates (Ittner).
In vivo mouse models (Ittner).
Interactome of candidate proteins (Ittner).
Combinatorial transgenics (Ittner).

See what’s going on at NeuRA

FEEL THE BUZZ IN THE AIR? US TOO.

Spinal Cord Injury Breakthrough

Researchers from NeuRA, the University of New South Wales
the University of Sydney,
and HammondCare have found surviving sensory spinal nerve connections in 50 per cent of people living with complete thoracic spinal cord injuries. The study, which is part of
a decade-long collaboration between the researchers, used cutting-edge functional MRI (fMRI) technology to record neural response to touch. It was  Dr Sylvia Gustin who analysed the fMRI images to identify the moment the patient’s brain registered the touch. “Seeing the brain light up to touch shows that despite the complete injury to the thoracic spine, somatosensory pathways have been preserved,” explains Dr Gustin. “It’s fascinating that although the patients did not ‘feel’ the big toe stimulation in the experiment, we were able to detect a significant signal in response to the touch in the brain’s primary and secondary somatosensory cortices, the thalamus, and the cerebellum.” For those living with a complete spinal cord injury this means, despite previously believing
the communication to the brain had been severed in the injury, messages are still being received. Dr Gustin describes this new category of spinal cord injury as ‘discomplete’ “The current classification system is flawed. It only contains two types of spinal cord injury – complete and incomplete,” says Dr Gustin. “It is important we acknowledge there is a third category – the ‘discomplete’ injury, only then we can provide better treatment regimens for the many sufferers of a complete spinal cord injury.” For those newly classified as ‘discomplete’, this discovery opens up new opportunities to identify those people living with a spinal cord injury that are more likely to benefit from treatments aimed at improving sensation and movement. Because of this study, research participant, James Stanley, now knows he belongs to a new category. “It is exciting to know that there
is a connection there, that my toe is trying to say hello to my brain,” says James. “If medical professionals can work to identify people like me with a ‘discomplete’ injury earlier, perhaps they can find new treatments and rehabilitation techniques. “The thought that one day I might be able to feel the sand between my toes again, or the waves wash over my feet gives me hope. It’s something Dr Gustin’s discovery has made possible.”
PROJECT