Neuroscience

Our group investigates the way neurological disorders develop.

We focus on understanding the cause of Mitochondrial diseases, Parkinson’s disease and a range of other movement disorders. We also provide diagnostic support for our large clinic for patients with mitochondrial diseases and movement disorders.

Our focus is to develop accurate methods of diagnosis and advance understanding of how genetic mutations cause neurological disease. Ultimately, we aim to translate the results of our research into improved clinical care for our patients with neurological disorders.

Starry galaxy: The image shows olfactory neural stem cells derived from a patient with a neurodegenerative disease. Cells have an active transport system working continuously to transport cargo to different parts of the cells. The "red dots" (cellular organelles) are transported along the green "railway tracks" (actin cytoskeleton). The nucleus shown in blue is the centre of the cell. The patient cell transport system is disrupted as a consequence of the disease gene mutation. Image credit: Dr Gautam Wali


Defining an individual’s disease-causing mutations provides clinicians and patients with information for appropriate treatment and genetic counselling. We use next-generation sequencing methods to discover and identify new gene mutations in individuals who may have unusual disease symptoms.

Our specific goal is to identify key molecular pathways involved in the development of neurological diseases, with a particular focus on mitochondrial function. To understand an individual’s genetic mutation, we use various methods including molecular biological techniques, mitochondrial function assays, biomarker measurement and patient derived stem cells to create in vitro models of neurological disease.

Our clinical studies are aimed at determining the natural history of mitochondrial diseases, identifying factors that can predict disease progression and severity, and developing tools to monitor disease progression to enhance the performance of clinical trials.

Funding sources include the National Health and Medical Research Council, the Mito Foundation, HSP Research Foundation, Parkinson’s NSW, the Hughie Foundation and the Rebecca Cooper Medical Research Foundation


Lead

Professor Carolyn Sue Professor Carolyn Sue AM

Director of the Kolling Institute
Director of Neurogenetics Laboratory
Director of Neurogenetics
Director of the Centre of Excellence for Parkinson’s Disease and Movement Disorders
Senior Staff Specialist in Department of Neurology at Royal North Shore Hospital
Director of the National Centre for Adult Stem Cell Research (Sydney Node)

Professor Sue is an internationally recognised expert on movement disorders and mitochondrial diseases. Working as a clinician scientist at the Kolling Institute and Royal North Shore Hospital, Professor Sue runs tertiary referral clinics for patients with complex neurogenetic conditions, including Parkinson’s disease, mitochondrial diseases and other inherited movement disorders.

Professor Sue completed her PhD at the University of Sydney in 1997 before carrying out her postdoctoral research at Columbia University in New York. She returned to Sydney in 2000 to establish her own research team at the Kolling Institute. Professor Sue currently leads a team including five postdoctoral scientists, four PhD students, and two research assistants.

Under her leadership, research in the Department of Neurogenetics focuses on bridging the gap between clinical and molecular science. Professor Sue has a major interest in understanding the disease processes involved in neurological disorders, with an emphasis on developing new treatment options for patients.

In 2019, Professor Sue was awarded the Order of Australia for significant services to medicine.

Dr Ryan Davis Dr Ryan Davis

NSW Health early-mid career research fellow

Dr Davis joined the Kolling Institute in 2011 after completing his PhD research at the University of Otago, Christchurch School of Medicine in New Zealand. He received an NHMRC Peter Doherty early career fellowship in his first year postdoctoral and is currently a NSW Health early-mid career fellow.

Dr Davis’ work focuses on bridging basic and clinical research of mitochondrial diseases and other neurogenetic conditions, using techniques including whole genome sequencing, metabolomics, molecular biology and mitochondrial function assays. Dr Davis works directly with the Neurogenetics Clinic at Royal North Shore Hospital to improve the diagnosis of these conditions and to better inform the treatment of patients.

Dr Davis also has a visiting scientist appointment at the Garvan Institute, where he is developing skills in the area of genomics working with the Translational Genome Informatics group at the Kinghorn Centre for Clinical Genomics.

Dr Gautam Wali Dr Gautam Wali

Research fellow, Kolling Institute for Medical Research, University of Sydney

Dr Wali joined the Kolling Institute as an early career post-doctoral scientist in 2016, after completing his PhD at Griffith University, Queensland. His research is focused on using patient-derived stem cell models: adult olfactory neural stem cells and induced pluripotent stem cells for disease modelling and drug screening for neurodegenerative diseases. He specialises in the use of high throughput drug screening assays to identify potential drug treatment candidates. He focuses on hereditary spastic paraplegia, Parkinson’s disease and Mitochondrial disorder patients. Gautam and colleagues have identified a potential drug treatment candidate for SPAST HSP and he is part of a six member team leading the Australian hereditary spastic paraplegia pre-clinical trial study.

For biomarker identification, Dr Wali uses proteomics to identify differentially expressing proteins in easily accessible patient samples, particularly blood, urine and skin cells.

Dr Wen Li Dr Wen Li

Postdoctoral Researcher, University of Sydney

Dr Li joined the Kolling Institute in 2019 as a postdoctoral scientist. She completed her PhD in molecular biology and immunology at the University of Sydney 2014. Dr Li has considerable experience in wide array of technical skills including molecular biology methodologies, cell culture (isolating primary brain cells), pathology practice and animal model of disease. The primary focus of her current research is to investigate the molecular mechanisms of mitochondrial quality control in Parkinson’s disease.

University of Sydney: Brain and Mind Centre, ForeFront Ageing and Neurodegeneration team

Garvan Institute: Kinghorn Centre for Clinical Genomics

1. Biomarkers of mitochondrial diseases.

Researcher: Dr Ryan Davis, Professor Carolyn Sue

Mitochondrial disease describes a wide range of progressive multi-system disorders caused by any one of over 300 different genetic mutations. Symptoms may appear at birth or later in life and the severity of disease is highly unpredictable. Mitochondrial diseases are extremely difficult to diagnose as symptoms overlap with many other common disorders.

Although there is no cure, it is important to identify which type of mitochondrial disease is present and understand the genetics of the disease. This will help ensure optimal clinical care and predict the risk of recurrence for the next generation. Using various techniques, including Nuclear Magnetic Resonance spectroscopy, we are working to define reliable biomarkers and establish a definitive metabolic diagnostic test for mitochondrial diseases.

2. Longitudinal gut microbiome changes in Parkinson’s disease patients.

Researchers: Dr Michal Lubomski (PhD candidate), Dr Ryan Davis, Professor Carolyn Sue, in collaboration with Professor Andrew Holmes and Professor Jean Yang at University of Sydney.

Research shows that an imbalance in the gastrointestinal microbiome may contribute to the development and progression of Parkinson’s disease. The ability to modulate the gastrointestinal microbiome to protect against or slow progression of Parkinson’s disease would revolutionise treatment of the disease. Our group is investigating changes in the composition of the gastrointestinal microbiome of Parkinson’s disease patients compared to healthy individuals, and how different Parkinson’s disease treatments influence the gastrointestinal microbiome. The study involves standard molecular biological techniques and next generation sequencing.

3. NIX-mediated Mitophagy: a new therapeutic approach to Parkinson’s disease.

Researchers: Dr Wen Li, Professor Carolyn Sue, in collaboration with Dr YuHong Fu and Professor Glenda Halliday at University of Sydney,

A treatment capable of slowing or preventing neuro-degeneration has the potential to substantially improve the lives of those suffering from Parkinson’s disease. Quality control of mitochondria (mitophagy) is essential for the survival and function of neurons. Genetic studies have shown that mitophagy is under the control of two genes called PINK1 and Parkin and that mutations in these genes can cause Parkinson’s disease. We are investigating whether a healthy population of mitochondria can be maintained in neurons affected by genetic forms of Parkinson’s disease, by activating mitophagy through an alternative route – the Nix pathway.

4. Patient-derived stem cell models to study disease mechanisms and screen drug candidates for Hereditary Spastic Paraplegia.

Researchers: Dr Gautam Wali, Professor Carolyn Sue, in collaboration with Professor Alan Mackay-Sim at Griffith University

Hereditary spastic paraplegia is a movement disorder in which the corticospinal motor neurons degenerate. The goal of our research program is to understand the cellular consequences of different hereditary spastic paraplegia mutations and find therapeutic drug candidates for each specific genotype. Our current focus is on the two most common forms of hereditary spastic paraplegia - - SPAST and SPG7 HSP. For this we use patient-derived adult olfactory neural stem cell and induced pluripotent stem cell models.

Neurons that fire together - wire together: The image shows a network of induced pluripotent stem cell-cortical neurons derived from a patient suffering a neurological disorder. While the red fluorescence identifies neurons (beta III tubulin), the green fluorescence identifies their inter-connectivity (Synapsin). Image credit: Dr Gautam Wali

5. Biomarker for Hereditary spastic paraplegia

Researchers: Dr Gautam Wali, Dr Sue-Faye Siow (PhD candidate), Dr Kishore Kumar, Professor Carolyn Sue

Hereditary spastic paraplegia results in significant disability with no curative or disease-modifying treatment. The lack of standardised biomarkers of disease severity has limited the evaluation of potential therapeutic agents. Our aim is to identify a biomarker for the disease by evaluating differential protein expression between hereditary spastic paraplegia patients and healthy controls. For this we use easily accessible patient samples including blood, urine and skin cells.

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