Motor Neurone Disease Group

Neurodegenerative diseases have a devastating impact on quality of life and impose a tremendous burden on the health care system. Motor neurone disease (MND) is the most rapidly fatal, with increasing physical disability and death typically within 2-3 years from the onset of symptoms.

Our group is primarily focused on understanding the molecular basis of MND, also called amyotrophic lateral sclerosis (ALS), to inform rational drug development for treatment. We also research other neurodegenerative diseases affecting motor neurons, including spinal muscular atrophy (SMA) and spinal bulbar muscular atrophy, more commonly known as Kennedy’s disease (KD).

Research interests

  • Motor neurone disease
  • Amyotrophic lateral sclerosis
  • Primary lateral sclerosis
  • Spinal muscular atrophy
  • Kennedy’s disease
  • Frontotemporal dementia
 Techniques

  • Stem cell technology
  • Advanced imaging techniques
  • Organoids
  • DREADDs
  • Multi-omics
  • Antisense oligonucleotides
  • High throughput drug screening
  • Animal behaviour
  • Neuropathology and molecular biology
  • Genetic engineering and genome editing
  • CRISPR screens

About our research

Our approach

We have a broad interest in developing and delivering new therapeutics for MND using pioneering stem cell and animal models.

Our group uses a combination of cell and molecular biology to unravel MND pathogenesis in patient-derived biosamples, cell culture systems and animal models. We seek to identify and understand the primary mechanisms underlying motor neuron vulnerability and degeneration in MND, while translating our discoveries into relevant targets for effective intervention.

We are particularly known for pioneering new and improved models of MND using induced pluripotent stem cell (iPSC) technology, organoids, chemogenetics and genome editing.

Key research questions we’re investigating include:

  • What is the fundamental cause of ALS?
  • When does motor neuron vulnerability start in ALS?
  • Where does ALS originate in the central nervous system?
  • What is the primary cell death pathway(s) mediating motor neuron loss in ALS?
  • How early do we need to intervene with treatments in ALS?
  • Do ALS, SMA and KD share a common pathogenesis?

Our major outcomes

  • Establishing a large-scale, population-wide library of induced pluripotent stem cells (iPSCs) from Australian MND patients pre-validated for disease phenotypes and drug efficacy (ID MND Initiative).
  • Establishing a multi-omic dataset from Australian MND patient iPSC-derived motor neurons combining deep longitudinal clinical, genomic, transcriptomic and metabolomic profiles to understand heterogeneity (Precision Medicine Program).
  • Our preclinical findings have directly contributed to five clinical trials for MND, including re-purposing of the generic drug ambroxol for ALS, which is currently under Phase 2 clinical trial.

‘Our research is empowered by the MND Community. From people with MND who generously donate precious cells to our drug screening program to the army of donors and patient-founded organisations who tirelessly support our research for a cure.’

 

Research team

Research team head

Professor Bradley Turner

Group Head

Team members

Dr Nirma Perera

Dr Mouna Haidar

Dr Sophia Luikinga

Senior Research Fellow

Dr Taide Wang

Research Fellow

Dr Azin Amin

Research Fellow

Dr Lin (Elizabeth) Qian

Research Fellow

PhD students

  • Jibao (Jack) Yuan
  • Lijun Loh
  • Roaul Das
  • Matteo Pitteri
  • Katherine Lewis
  • Chau Tran
  • Aida Viden
  • Francois-Xavier Beau

Research and technical staff

  • Doris Tomas
  • Dhanushka Wanniarachchillage
  • Katherine Lim
  • Brittany Cuic

Selected publications

  • Wang T, Tomas D, Perera ND, Cuic B, Luikinga S, Viden A, Barton SK, McLean CA, Samson AL, Southon A, Bush AI, Murphy JM and Turner BJ (2021), ‘Ferroptosis mediates selective motor neuron death in amyotrophic lateral sclerosis’, Cell Death & Differentiation, 29(6):1187–1198, doi:10.1038/s41418-021-00910-z
  • Perera ND, Tomas D, Wanniarachchillage N, Cuic B, Luikinga SJ, Rytova V and Turner BJ (2021), ‘Stimulation of mTOR-independent autophagy and mitophagy by rilmenidine exacerbates the phenotype of transgenic TDP-43 mice’, Neurobiology of Disease, 154:105359, doi:10.1016/j.nbd.2021.105359
  • Wang T, Perera ND, Chiam MDF, Cuic B, Wanniarachchillage N, Tomas D, Samson AL, Cawthorne W, Valor EN, Murphy JM and Turner BJ (2019), ‘Necroptosis is dispensable for motor neuron degeneration in a mouse model of ALS’, Cell Death & Differentiation, 27(5):1728–1739, doi:10.1038/s41418-019-0457-8
  • Sheean RK, McKay FC, Cretney E, Bye CR, Perera ND, Tomas D, Weston RA, Scheller KJ, Djouma E, Menon P, Schibeci SD, Marmash N, Yerbury JJ, Nutt SL, Booth DR, Stewart GJ, Kiernan MC, Vucic S and Turner BJ (2018), ‘Association of regulatory T-cell expansion with progression of amyotrophic lateral sclerosis, JAMA Neurology, 75(6):681, doi:10.1001/jamaneurol.2018.0035
  • Perera ND, Sheean RK, Lau CL, Shin YS, Beart PM, Horne MK and Turner BJ (2018), ‘Rilmenidine promotes MTOR-independent autophagy in the mutant SOD1 mouse model of amyotrophic lateral sclerosis without slowing disease progression’, Autophagy, 14(3):534–551, doi:10.1080/15548627.2017.1385674

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