Motor Neurone Disease Laboratory
Neurodegenerative diseases have a devastating impact on quality of life and impose a tremendous burden on the health care system.
Among neurodegenerative conditions, motor neurodegenerative diseases are the among the most rapidly fatal, with increasing disability and death within 2-3 years from symptom onset.
Our laboratory is primarily focused on understanding the molecular basis of motor neuron disease (MND), also called amyotrophic lateral sclerosis (ALS). We are also interested in other motor neurodegenerative disorders, including spinal muscular atrophy (SMA) and spinal bulbar muscular atrophy (SBMA), more commonly known as Kennedy's disease.
Our team employs a combination of cell and molecular biology to unravel MND pathogenesis in patient-derived samples, cell culture and animal models. We seek to identify and understand the primary mechanisms underlying motor neuron vulnerability, stress and injury in MND, while translating our discoveries into relevant biomarkers and targets for effective intervention. Our group is particularly interested in the molecular determinants of protein misfolding and accumulation within neurons, and harnessing endogenous cellular protective mechanisms to combat protein misfolding. We also investigate mechanisms of misfolded protein propagation in the central nervous system in MND with the goal to arrest disease spread.
A further area of investigation is the therapeutic action of survival motor neuron (SMN) protein for SMA and MND. We have discovered that SMN restoration slows disease progression and improves motor neuron survival in mouse models of MND, in addition to SMA mouse models. This has led to development of motor neuron targeted SMN gene therapy approaches for both SMA and MND
Our research at a glimpse
- Developing an antisense therapy approach for Kennedy’s disease
- Development of BBB-permeable ASO for selective knockdown of ataxin-2 to abrogate TDP-43 proteinopathies as a broad therapeutic strategy for ALS
- Development of peptide-oligonucleotide conjugates to knockdown poly(ADP-ribose) polymerase as a novel RNA-based therapy for amyotrophic lateral sclerosis
- Making neuromuscular junctions in vitro using patient-derived induced pluripotent stem cells
- Using patient induced pluripotent stem cells to determine the role of astrocytes in disease
- Using patient induced pluripotent stem cells to determine the role of oligodendrocytes in disease
- Making brain organoids from patient-derived induced pluripotent stem cells
- Using novel mouse models to determine the role of oligodendrocytes in disease
- Using DREADDs to deconstruct motor neuron disease
- Investigating autophagy inducers as a therapeutic strategy for motor neuron disease
- Investigating the autophagy pathway in a novel C9ORF72 mouse model of motor neuron disease
- Using gene expression profiling to understand selective cell vulnerability in MND
- Defining unique molecular markers of upper motor neurons in MND
- Mapping the origin and onset of MND - Transcriptomic profiling of motor neuron populations in MND.
- Generating novel mouse models of Kennedy’s disease
- Developing SMN gene therapy for SMA and MND
- Targeting exosome-mediated propagation of protein misfolding in MND
- Stimulating autophagy to improve intracellular proteostasis in MND
Prof Dame Kay Davies and Prof Kevin Talbot, University of Oxford
Dr Severine Boillee, Brain and Spine Institute, Paris
Prof Neil Cashman, University of British Columbia
Prof Uri Saragovi, McGill University
Prof Steve Vucic, University of Sydney
Dr Mary-Louise Rogers and Dr Hakan Muyderman, Flinders University
Dr Justin Yerbury, University of Wollongong
Prof Julie Atkin, Macquarie University
Assoc Prof Danny Hatters, University of Melbourne
Prof Philip Beart and Prof Malcolm Horne, University of Melbourne
Australian National Health and Medical Research Council
Bethlehem Griffiths Research Foundation
Motor Neuron Disease Research Institute of Australia
Balcon Group Pty Ltd
SciOpen Research Group
Stafford Fox Medical Research Foundation
State Government of Victoria
Brain health affects all Australians. You can support our research by making a donation or a bequest.