Biophysics |Neuroscience |Drug Discovery |
Our facility
A core unit within the Translational Neuroscience Facility in the School of Biomedical Sciences, UNSW Sydney, directed towards treatment of neurological disorders. Collaborating teams focus on therapeutic applications linked to hearing loss, leukodystrophies (genetic disorders that affect the CNS white matter), neuroprotection in stroke and traumatic brain injury, neuro-immunological basis of neuropathic pain, neural regeneration, CNS neural plasticity underlying memory & addiction; neural coding; industry collaborations in small molecule and DNA / RNA therapeutics supporting translation through novel therapeutic approaches for reducing brain injury from stroke, brain trauma & epilepsy. Targeting gene expression in the nervous system; adeno-associated virus viral vector core; proprietary non-viral focal gene electrotransfer (BaDGE®); multiphoton physiological imaging; electrophysiology; transgenic mouse models of CNS pathophysiologies.
Our Research
The Sensori-Motor Physiology & Therapeutics (SMPT) research program spans neuro-protection, neuro-repair, medical bionics, and DNA therapeutics targeting the nervous system and muscle function. A principal area of research concerns the molecular and cellular basis of hearing loss focusing on cell signalling that contributes to sensory hair cell injury and auditory synaptopathy due to noise and aging.
An applied arm is the development of BaDGE® (bionic array – directed gene electrotransfer) which in a first-in-human clinical trial is enabling targeted delivery of DNA encoding neurotrophin genes into the cochlea to stimulate regeneration of the auditory nerve fibres in cochlear implant recipients. BaDGE® is a platform technology for precise delivery of naked DNA throughout the body, including brain and muscle.
The SMPT program extends to neuroprotection studies directed at reduction of excitotoxicity driving synaptopathy and brain injury, and neuromodulation in targeted brain regions with application across stroke, TBI, epilepsy & Parkinson’s Disease.
Neuroprotection and Nerve Repair (small molecule and DNA/mRNA therapeutics)
Models of stroke – photothrombotic infarcts |
Ion channel & G protein-coupled receptor – based Ca2+ signalling drug targets |
Models of traumatic brain injury |
Epilepsy and related focal neurological |
Gene-based therapeutics for nerve injury and muscle reinnervation
Highlighted publications
- Jeremy L. Pinyon, Georg von Jonquieres, Stephen L. Mow, Amr Al Abed, Keng-Yin Lai, Mathumathi Manoharan, Edward N. Crawford, Stanley H. Xue, Sarah Smith-Moore, Lisa J. Caproni, Sarah Milsom, Matthias Klugmann, Nigel H. Lovell, Gary D. Housley. ‘Vector-Free Deep Tissue Targeting of DNA/RNA Therapeutics via Single Capacitive Discharge Conductivity-Clamped Gene Electrotransfer’, Advanced Science 3/2025 ()
- Gene Electrotransfer via Conductivity-Clamped Electric Field Focusing Pivots Sensori-Motor DNA Therapeutics: “A Spoonful of Sugar Helps the Medicine Go Down” Advanced Science 30/2024. Jeremy L. Pinyon, Georg von Jonquieres, Edward N. Crawford, Amr Al Abed, John M. Power, Matthias Klugmann, Cherylea J. Browne, David M. Housley, Andrew K. Wise, James B. Fallon, Robert K. Shepherd, John Y. Lin, Catherine McMahon, David McAlpine, Catherine S. Birman, Waikong Lai, Ya Lang Enke, Paul M. Carter, James F. Patrick, Robert D. Gay, Corinne Marie, Daniel Scherman, Nigel H. Lovell, Gary D. Housley
- Achanta LB; Thomas DS; Housley GD; Rae CD, 2023, 'AMP-activated protein kinase activators have compound and concentration-specific effects on brain metabolism', Journal of Neurochemistry,
- Kalotay E; Klugmann M; Housley GD; Fröhlich D, 2023, 'Dominant aminoacyl-tRNA synthetase disorders: lessons learned from in vivo disease models', Frontiers in Neuroscience, 17,
- Kalotay E; Klugmann M; Housley GD; Fröhlich D, 2023, 'Recessive aminoacyl-tRNA synthetase disorders: lessons learned from in vivo disease models', Frontiers in Neuroscience, 17,
- Parmar J; von Jonquieres G; Gorlamandala N; Chung B; Craig AJ; Pinyon JL; Birnbaumer L; Klugmann M; Moorhouse AJ; Power JM; Housley GD, 2023, 'TRPC Channels Activated by G Protein-Coupled Receptors Drive Ca2+ Dysregulation Leading to Secondary Brain Injury in the Mouse Model', Translational Stroke Research,
- Cederholm JME, Parley KE, Perera CJ, von Jonquieres G, Pinyon JL, Julien J-P., Ryugo DK, Ryan AF,Housley GD (2022) Noise-induced hearing loss vulnerability in type III intermediate filament peripherin gene knockout mice. Frontiers in Neurology- Neuro-Otology. In: Current Knowledge and Further Development in the Field of Otoprotection.Sep 26;13:962227. doi: 10.3389/fneur.2022.962227. eCollection 2022.PMID:36226085.
- Jennie M E Cederholm, Allen F Ryan, Gary D Housley (2019). Onset kinetics of noise-induced purinergic adaptation of the 'cochlear amplifier'. DOI: 10.1007/s11302-019-09648-3
- Gary D. Housley, Rachel Morton-Jones, Srdjan M. Vlajkovic, Ravindra S. Telang, Vinthiya Paramananthasivam, Sherif F. Tadros, Ann Chi Yan Wong, Kristina E. Froud, Jennie M. E. Cederholm, Yogeesan Sivakumaran, Peerawuth Snguanwongchai, Baljit S. Khakh, Debra A. Cockayne, Peter R. Thorne, and Allen F. Ryan (2013). ATP-gated ion channels mediate adaptation to elevated sound levels.
- Denise Yan, Yan Zhu, Tom Walsh, Dinghua Xie, Huijun Yuan, Asli Sirmaci, Taro Fujikawa, Ann Chi Yan Wong, Tze L. Loh, Lilin Du, M’hamed Grati, Srdjan M. Vlajkovic, Susan Blanton, Allen F. Ryan, Zheng-Yi Chen, Peter R. Thorne, Bechara Kachar, Mustafa Tekin, Hong-Bo Zhao, Gary D. Housley, Mary-Claire King, Xue Z. Liu (2013). Mutation of the ATP-gated P2X2 receptor leads to progressive hearing loss and increased susceptibility to noise.
- The Team
- Adjunct team members
A vibrant group of research scientists with expertise in Auditory Neuroscience, Cell and Molecular Biology, Gene therapy, Neuroimmunology, Neurophysiology, Electrophysiology and CNS disorders.
Capabilities
- Neurophysiology
- Optogenetics
- Intravital multiphoton imaging
- Genetically-encoded Ca2+ reporter brain injury readout
- Brain slice patch-clamp ion channel studies
- Evoked field potential electrophysiology (auditory & visual)
- AAV viral vector gene core
- Mouse transgenics & behavioural phenotyping
- BaDGE® platform for gene electrotransfer therapeutics
Impact and Applications
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The CINGT trial is a first-in-human, phase I/II non-randomized, controlled trial, evaluating the safety and efficacy of neurotrophin gene therapy delivered during cochlear implant surgery. The neurotrophin treatment, administered during cochlear implant surgery, encourages the cochlear nerve fibres to regrow close to the cochlearClinical study: Noise-induced hearing adaptation: a biomarker for hearing loss vulnerability (Interacoustics Partner)
- UNSW team (Prof Gary Housley, Dr. Jeremy Pinyon (adjunct), Dr. Georg von Jonquieres, Dr. Fadwa Alnafjan (adjunct), Edward Crawford, Mayryl Duxbury)
- Collaborators: Cochlear Ltd, Australian Hearing Hub (Macquarie University), NextSense Australia.
Related links:- Trial website:
- Australian New Zealand Clinical Trials Registry:
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This project seeks to establish the characteristics of the cochlea’s response to noise stress with the view that the more dynamic the adaptation to sustained noise, the more resistant the subject’s ears are to noise damage. On this basis, we are developing a prognostic test for individuals vulnerable to hearing loss (hearing loss vulnerability test-HLVT), who may be identified by a reduced adaptation to a noise stress test.
- Team leaders, Prof Gary Housley, A/Prof Jennie Cederholm, Dr. Frederic von Wegner
- Collaborators: Australian Hearing Hub (Macquarie University), Department of Audiology (University of Auckland), Dept. Otolaryngology, (University of Miami), Otolaryngology (University of California San Diego), Shanghai Neuroscience Institute (Chinese Academy of Science), Otolaryngology (Shinshu University, Matsumoto, Japan).
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This collaborative research program supports the development of a new class of small molecule neuroprotective drug directed to reducing secondary brain injury by targeting a class of ion channels (TRPC) which our group and others have recently shown to cause pathophysiological calcium loading in neurons and glial cells linked to dysregulated neurotransmitter release.
- Dr. Georg von Jonquieres (Team Leader), Dr. Jasneet Parmar (Nyrada Inc. Team Leader & Adjunct).
- Collaborators: Nyrada Inc., Watler Reed Army Institute for Research
- Related links:
- Parmar J, von Jonquieres G, Gorlamandala N, Chung B, Craig AJ, Pinyon JL, Birnbaumer L, Klugmann M, Moorhouse AJ, Power JM, Housley GD (2023) TRPC channels activated by G protein-coupled receptors drive Ca2+dysregulation leading to secondary brain injury in the mouse model. Transl Stroke Res. 2024 Aug;15(4):844-858. doi: 10.1007/s12975-023-01173-1.
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Supported by an NHMRC Ideas Grant, this project refines the brain-BaDGE® platform to achieve scalable targeted gene electrotransfer to DNA and mRNA-based therapeutics in the CNS. The collaborating team has developed a novel plasmid DNA therapeutics encoding ion channels which will suppress hyperexcitability in brain circuits (relevant to control of focal epilepsy and Parkinson’s disease).
- Team leaders, Prof Gary Housley, Dr. Georg von Wegner, Dr. Frederic von Wegner, A/Prof Jennie Cederholm, Dr. Dominik Froelich, Dr. Jeremy Pinyon (adjunct).
- Collaborators: Boehringer-Ingelheim Germany, Touchlight Genetics UK, Hertie Institute for Clinical Brain Research (Tuebingen Germany)
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Vision. This ‘Vision-BaDGE®’ program (funded by Australia’s Economic Accelerator Ignite Program) is directed to using novel plasmid DNA therapeutics delivered to the white of the eye by gene electrotransfer to suppress VEGF-based neovascularisation (the cause of wet aged-related macular degeneration).
- Team leaders, Prof Gary Housley, Dr. Georg von Jonquieres, A/Prof Jennie Cederholm, Edward Crawford, Amr Abed, Prof Nigel Lovell, Mohit Shivdasani, Dr. Dominic Froelich, Dr. Jeremy Pinyon (adjunct), Mayryl Duxbury, Dr. Ian Goon, Dr. Lily Pearson
- Collaborators: Boehringer Ingelheim, Touchlight Genetics UK, IDE Group
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Gary Housley - Group Leader
Gary Housley, PhD, holds the Chair of Physiology and is director of the Translational Neuroscience Facility, School of Medical Sciences, UNSW Australia. His research program is broadly within molecular, cellular and systems physiology in the nervous system, particularly around neuroprotection in the CNS and auditory system. He has contributed prominently to understanding how hearing adapts to noise and ageing. Study of neural development and synaptic plasticity in the auditory system informs on gene-targets for neural repair. This research has an applied arm with respect to bionics such as the cochlear implant which has led to development of an innovative gene therapy platform for auditory nerve regeneration which is currently in a first-in-human clinical trial (www.cingt.info). Hearing loss is the most prominent sensory disability in our society. Stroke is the third highest killer and the most disabling for survivors. Leader for development of UNSW Sydney patented technology for delivery of DNA and RNA therapeutics. BaDGE® - Bionic array Directed Gene Electrotransfer.
Within the brain, Housley's research group are investigating neural plasticity associated with driven input ( e.g. via the cochlear implant) and mechanisms for protection and repair of the nervous system (focusing of the role of calcium signalling in excitotoxicity, associated with ischaemic brain injury, stroke, epilepsy and traumatic brain injury. The research is supported by national and international collaborations and funding.
Collaborators
Prof. Allen Ryan (Univ. California, San Diego, USA); Prof. Peter Thorne, Dr. Srdjan Vlajkovic (University of Auckland, New Zealand), Prof. Jean-Pierre Julien (Laval University, Quebec, CAD), Prof. Lutz Birnbaumer (Buenos Aires, Argentina) Prof. Shin-ichi Usami (Shinshu Univ., Japan); Prof. Junichi Nabekura (National Institute of Physiological Sciences, Okazaki, Japan)
BaDGE® - CINGT collaborators: Scientia Prof. Nigel Lovell (UNSW); A/Prof. Matthias Klugmann (UNSW); Prof. Daniel Scherman and Dr. Corinne Marie (School of Pharmacy, Descartes, Paris), Prof. Anne Schielder (Otolarynology, UCL, London); Ya Lang Enke (Cochlear), Paul Carter (Cochlear), Jim Patrick (Cochlear), Saji Maruthurkkara (Cochlear), Lisa Nelson (UNSW), Catherine Birman (Sydney Cochlear Implant Centre), Colleen Psarros (Sydney Cochlear Implant Centre), Wai Kong Lai (Sydney Cochlear Implant Centre), Halit Sanli (Sydney Cochlear Implant Centre), Catherine McMohan (Macquarie University), David McAlpine (Macquarie University), Jaime Undurraga (Macquarie University), Fiona Odams (Macquarie University), Phillip Nakad (Macquarie University), Robert Shepherd (Bionics Institute), James Fallon (Bionics Institute), Andrew Wise (Bionics Institute).
Industry partners
Cochlear Ltd (Dr. Jim Patrick , Dr. Martin Svehla)
Roche Palo Alto (Dr. Deborah Cockayne)
Nyrada Inc.
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