The Drug Discovery Lab is interested in finding new treatments and detection methods for CNS diseases like frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer’s disease and disorders involving neuroinflammation. Available projects will use techniques such as tissue culture, iPSCs, 3D printing, transfection, cellular assays, immunohistochemistry, radioligand binding, PCR, sequencing and western blots to find new drug targets, screening models and therapeutics for these diseases.
In the Kassiou group, we design and synthesise novel small molecules that target a range of diseases that affect the central nervous system. We also perform pharmacological assays to validate and assess our compounds. The work in our laboratories has led to the establishment of spin-off companies and first-inhuman trials of drug candidates. The projects below are only a sample of what we can offer, and projects can be tailored to suit the specific interests of any prospective students.
Projects available
Conditions that commonly overlap with social withdrawal (SW) include depression, autism, addiction and social anxiety, among others. These might be considered as either the cause or the symptoms of SW. We are designing compounds that target the oxytocin receptor as a way of treating SW to target multiple disease states. Oxytocin (OT) is a 9-amino acid cyclic peptide that exerts prosocial effects in mammals through activation of the OT receptor. However, as an oligopeptide it is a poor drug candidate and is not brain permeable. This project involves the synthesis of non-peptidic OT receptor agonists to elucidate how their chemical structure influences biological activity.
For more information contact Michael Kassiou E: micheal.kassiou@sydney.edu.au
One of the causes of disease progression in neurodegenerative disorders (e.g. Alzheimer’s disease) is the malfunctioning and aggregation of tau protein. To date, research efforts involving single target approaches for treating tauopathies have not resulted in the discovery of any disease modifying therapies. However, multi-targeted strategies have shown promise and are being pursued at an increasing rate. Currently we are developing compounds that modulate tau phosphorylation, promote tau clearance and inhibit tau aggregation. The long-term aim is to merge the pharmacophores of various combinations of these targets, to generate multi-target tau aggregation inhibitors. This project will continue work towards the synthesis of ligands to develop structure-activity relationships for the above targets.
For more information contact Michael Kassiou E: micheal.kassiou@sydney.edu.au
Immune cells in the brain can be activated in response to various events, including infection or traumatic brain injury, which in turn leads to neuroinflammation and then neurodegenerative diseases. We develop small molecules that work against neuroinflammation as a treatment for these diseases. We also have a significant focus on imaging the neuroinflammation process by developing compounds for PET imaging. To achieve these goals, we are targeting two receptors: TSPO and P2X7. First-generation PET tracers for TSPO exhibit high levels of non-specific binding and thus low signal-to-noise ratios (SNR), making them of limited use in detecting subtle fluctuations of TSPO expression. Second-generation ligands with improved SNR have been developed in recent years but suffer from undesirable binding affinity variation within the population due to a genetic variation in TSPO expression. This project will continue work towards synthesising ligands which overcome both hurdles, displaying high specificity and a “one-size-fits-all” binding affinity regardless of genetic polymorphism.
The P2X7 receptor plays an essential role in inflammatory signalling as its activation leads to the formation and release of interleukin-1b, a proinflammatory cytokine which plays a major role in the inflammatory pathways underlying neurodegenerative processes. Our work involves developing ligands that bind to the P2X7 receptor to inhibit its activation.
For more information contact Michael Kassiou E: micheal.kassiou@sydney.edu.au
The Brain and Mind Centre is a world-leading research multidisciplinary research group with common goal: the development of better treatments for conditions of the brain and mind, improving health outcomes now and for future generations. We aim to understand individual circumstances and to develop solutions that improve the quality of life for both patients and their loved ones. The centre focuses on conditions that affect child development, youth mental health and brain ageing.
The Dementia and Movement Disorders Lab is led by Professor Glenda Halliday. It is a multidisciplinary research group investigating neurodegenerative dementias (primarily frontotemporal lobar degenerations, dementia with Lewy bodies, and Alzheimer’s disease), motor neuron disease, and neurodegenerative movement disorders (primarily Parkinson’s disease, multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration). Our focus is on understanding the tissue changes associated with neurodegenerative dementias and movement disorders in order to develop mechanistic treatments and diagnostic tools. Our research is aimed at identifying early versus later events in neurodegenerative disorders, both aspects suitable for targeting to either arrest disease onset or stop progression once the disease has begun, and also to more reliably detect the underlying protein changes in patients. In addition to the laboratory work, our studies involve the co-ordination of clinical studies that longitudinally follow patients with diagnoses of neurodegenerative movement disorders and dementias, and non-affected controls.
Our Frontotemporal dementia research group, part of the Dementia and Movement Disorder (DAMD) laboratory based at the Brain and Mind Centre (BMC), undertakes technical operations for the collection, preparation, archiving and analysis of blood and other biospecimen samples from patients for the development of biomarkers. The overall aim of the program is identify unique profiles of proteins, lipids, endogenous retroviruses and other molecular markers that can be measured and used to accurately distinguish different pathological forms of dementia from each other, particularly different types of frontotemporal temporal dementia, and other neurodegenerative diseases.
Projects available:
Coming soon
The Alzheimer’s disease research group is part of the Dementia and movement Disorder (DAMD) Lab at the Brain and Mind Centre (BMC). The goal of our research is to identify new drug targets and biomarkers for Alzheimer’s disease by comprehensively mapping all the protein changes that occur in the brain during Alzheimer’s disease. We are particularly interested in identifying protein changes that are closely associated with the characteristic neuropathological features present in Alzheimer’s disease brains (amyloid plaques and neurofibrillary tangles) and those found in neuron populations that are particularly vulnerable in the disease. To do this we use a state-of-the-art proteomics approach that allows us to map thousands of protein changes at once, which provides a bird’s eye view of the disease process in Alzheimer’s disease and allows us to pinpoint those particular protein changes that are new potential drug targets or biomarkers. We are also currently working with the most promising new drug targets that we have identified so far to determine how they are involved in Alzheimer’s disease.
Projects available:
Coming soon
Dementia with Lewy body is a difficult disease to work on as it overlaps with both Alzheimer’s disease and Parkinson’s disease clinically and pathologically. Because of this overlap, it is a more rapidly progressing disease. Nearly everyone with this disorder has amyloid deposition in their brain but they also deposit alpha-synuclein protein in their brain cells (distinguishing them from Alzheimer’s disease). Our Dementia with Lewy Body research group, part of the Dementia and Movement Disorder (DAMD) laboratory based at the Brain and Mind Centre (BMC), seeks to determine what is different about the mechanisms underlying this disease so that we can find novel treatments.
Projects available:
Coming soon
Motor neuron disease primarily affects the motor system and is very rapidly progressive. RNA binding proteins are largely affected but the mechanisms involved are still poorly understodd, except for genetic forms of the disease (a minority of people). Our Dementia with Lewy body research group is part of the Dementia and Movement Disorder (DAMD) laboratory based at the Brain and Mind Centre (BMC) aims to determine the cell types involved, when they become abnormal and what is the principal change that could be targeted therapeutically.
Projects available:
Coming soon
Our Parkinson's disease research group, part of the Dementia and Movement Disorder (DAMD) laboratory based at the Brain and Mind Centre (BMC), is trying to understand the causes of Parkinson's disease and related neurodegenerative movement disorders. In particular we focus on genetic causes of Parkinson's disease and whether the genes and proteins involved can be therapeutically targeted to treat Parkinson's disease, and/or be used as biomarkers for earlier diagnosis.
Projects available:
Coming soon
Our Multiple System Atrophy research group, part of the Dementia and Movement Disorder (DAMD) laboratory based at the Brain and Mind Centre (BMC), is investigating the cellular and molecular changes associated with multiple system atrophy (MSA). MSA is a devastating neurodegenerative disease that overlaps clinically with Parkinson’s disease. We assess a number of factors, including genetic makeup, brain tissue degeneration, and protein and lipid changes. Our overall research is to determine the pathogenic mechanism underlying the disease and to identify molecular targets that could be used to develop therapeutic strategies.
Projects available:
Coming soon
The Neurodegeneration Research Laboratory is led by Kay Double. Our research focusses on identifying cellular pathways responsible for brain cell death in degenerative disorders, including Parkinson’s disease, motor neurone disease, and dementia disorders, and developing and testing treatments to slow or halt the disease process. Recently they have identified a new type of abnormal protein in Parkinson’s disease which is thought to be associated with brain cell damage. They are also developing novel methods to image disease-associated changes in the brain and spinal cord to improve diagnosis and monitor treatment effects. Research student positions are available at Honours, Masters or PhD level for the projects below, please contact Prof Double for details.
The Motor neuron disease research team in the Neurodegeneration Research Laboratory, based at the Brain and Mind Centre (BMC), are working to understand why particular cells in the nervous system die, including motor neuron disease. Our ultimate aim is to develop and test treatments that can prevent this devastating disease. We are particularly interested in the role of metals, and metal-dependent proteins, in the nervous system. We have identified that copper is reduced in motor neuron disease brain tissue, and are developing the first tool to quantify and assess the distribution of copper in the living brain. This outcome would be a significant advance toward using CNS copper as a disease biomarker, and for monitoring the safety and efficacy of treatment of disorders of central copper dysfunction.
Projects available:
Coming soon
The Parkinson's disease research team in the Neurodegeneration Research Laboratory based at the Brain and Mind Centre (BMC) are working to understand why particular cells in the nervous system die, including Parkinson’s disease. Our ultimate aim is to develop and test treatments that can prevent this devastating disease. We are particularly interested in the role of metals, and metal-dependent proteins, in the nervous system. We have identified that copper is reduced in Parkinson’s disease brain tissue,and are developing the first tool to quantify and assess the distribution of copper in the living brain. This outcome would be a significant advance toward using CNS copper as a disease biomarker, and for monitoring the safety and efficacy of treatment of disorders of central copper dysfunction. We recently identified a new type of abnormal protein in the brains of patients with Parkinson’s disease and we are supported by national and international funding bodies to understand how this protein might contribute to brain cell death in Parkinson’s disease. Our work is highly collaborative; we work together with experts in many fields in Australia and internationally to meet this challenge.
Projects available:
Coming soon
Our research team investigates genes that are mutated in dementia and related neurodegeneration, particularly frontotemporal dementia (FTD) and motor neuron disease (MND). Our research straddles multiple steps on the pathway from genetic disease to targeted therapy. We use whole-exome and whole-genome DNA sequencing data from dementia patients to identify potentially pathogenic DNA variants in candidate genes. We are also developing high-throughput cellular assays of dementia-relevant biological phenotypes, such as subcellular localisation and aggregation of key pathological proteins. We are using these to determine pathogenicity of DNA variants in known dementia genes, and prioritise variants in novel candidate genes for further analysis. In addition, we perform in-depth characterisation of candidate disease genes using molecular biological and cell culture assays.
Projects available:
Coming soon
The FRONTIER Research Group, established in 2007, is the largest specialist fronto-temporal dementia (FTD) clinic in Australia. We specialise in the diagnosis, prognosis, and care of people with FTD and related conditions. Our clinic is located at the Brain and Mind Centre in the University of Sydney and is integrated with the ForeFront collaborative research network.
We work with patients with FTD and Alzheimer's disease, as well as related diseases, including corticobasal syndrome and progressive supranuclear palsy. We also aim to assist carers through all stages of their journey through education, psychosocial support, and referral to specialist services. You can find more information about our work, including detailed information on the FTD syndromes and resources for carers, on our website.
Our work is supported by the government through the National Health and Medical Research Council, university funding, and community donations.
Projects available:
Coming soon
One of the most enduring questions in the field of cognitive neuroscience is the matter of how memories are formed. In short, how do we remember the past? Why are our memories so vulnerable in dementia, and how does this impact the individual’s sense of self? Despite significant advances in this field, the underlying mechanisms of human memory remain a topic of vigorous debate and robust empirical research, and represent a question that lies at the heart of understanding what makes us unique as individuals.
The Memory and Imagination in Neurological Disorders team (MIND) aims to tackle these questions by studying how memory and related processes break down in younger-onset dementias. Over the last 5 years, we have demonstrated that memory is differentially affected across the frontotemporal lobar degeneration spectrum, reflecting the breakdown of different neurocognitive mechanisms. Our work further reveals that the capacity to imagine the future, to engage in creative cognition, and to mind wander or daydream, is markedly affected in dementia syndromes. We are building on these findings to understand how alterations in large-scale brain networks disrupts a range of uniquely human functions and how this impacts the sense of self and wellbeing in the affected individual.
Projects available:
Coming soon
Our research group is committed to work predicting, diagnosing and treating Dementia with Lewy Bodies (DLB), along with its most troubling symptoms. This work will utilise genetics and biomarkers along with clinical trials, neuroimaging, neurophysiology and other approaches to improve our understanding of a range of problems including cognitive decline and hallucinations. Currently, there are high rates of under- and mis-diagnosis, which can impact upon good management. In addition, our research is exploring ways to identify those people at high risk of developing DLB by recognising the significance of dream enactment.
Projects available:
Coming soon
The Healthy Brain Ageing (HBA) research program focuses on identifying, understanding and managing risk and protective factors that may impact the onset and trajectory of cognitive decline in people aged over 50 years, where the opportunity for dementia prevention is likely to be optimal. Our collaborative team of researchers, clinicians and students have internationally renowned expertise in key areas including cognition, sleep, depression, cardiometabolic health, digital health technologies, and cognitive intervention, and how these factors relate to cognitive decline and brain degeneration. Drawing on world-class facilities at the Brain and Mind Centre and within our research partner sites (including Charles Perkins Centre and Woolcock Institute of Medical Research), we utilize cutting-edge, evidence-based techniques and explore novel research paradigms for assessment and management of cognition, neurobiological markers of disease, sleep-wake disturbance and psychological wellbeing.
At the heart of the Healthy Brain Ageing program is our ‘one-of-a-kind’ early intervention research clinic serving adults aged over 50 years with recent concerns (i.e. within the last 5 years) regarding changes in their memory or other thinking skills, or mood disturbance (e.g. depression). The clinic is serviced by a multidisciplinary team including geriatricians, neuropsychologists, neurologists and research psychologists, all of whom are committed to providing clinical and research excellence. In addition to comprehensive assessment, the clinic also incorporates individualised and group-based programs targeting depression, sleep, nutrition, physical exercise, cognitive training, and a range of continually-evolving, novel approaches to optimizing ‘healthy brain ageing’.
Projects available:
Coming soon
The ForeFront Neurology clinic offers diagnostic assessment for patients and multidisciplinary symptom management. Our diagnostic team are able to perform electrodiagnostic studies including electromyography and nerve conduction studies, as well as novel procedures such as nerve and muscle ultrasound, peripheral nerve excitability and transcranial magnetic stimulation, the latter used to study brain function. Our multidisciplinary clinic incorporates a team of Neurologists, Clinical Nurse Specialist, Clinical Neuropsychologists, Occupational Therapy, Physiotherapy, Respiratory physician, Respiratory physiotherapists, Gastroenterology and a Neurology Clinical Coordinator.
Projects available
Neurodegeneration affects the brain on a systems level, significantly altering the structure and functional organisation of inter-regional communication across diffuse brain regions. This project uses a multi-modal neuroimaging approach to identify unique neural signatures of disease across clinical phenotypes of motor neuron disease and dementia. The research aims to model the evolution of structural and functional brain abnormalities and their association with clinical symptoms and functional impairment in patients. Experimental measures include: multi-modal neuroimaging, neuropsychological assessment, biomarkers.
For more information contact Sicong Tu E: sicong.tu@sydney.edu.au
Subcortical brain structures play a central role in the integration and modulation of neural signalling from the brainstem to cortical mantle. Advances in static and dynamic high field neuroimaging now allow unprecedented precision in delineating the structure and function of the pathways and sub-nuclei of deep-brain structures. This research aims to use novel multi-modal neuroimaging techniques to define the functional and neuromodulatory role of deep brain sub-nuclei in large scale brain networks and cognition. Experimental measures include: composite structural imaging, functional MRI, multi-shell diffusion MRI, MR spectroscopy (1H; 31P).
For more information contact Sicong Tu E: sicong.tu@sydney.edu.au
Episodes of uncontrolled laughter or crying that are misaligned with social and environmental context is a debilitating clinical symptom present across neurodegenerative conditions, in particular motor neuron disease and certain dementias. This project takes a multi-disciplinary approach to examine the cognitive, neural, and physiological basis of PLC, its association with progressive neurodegenerative mechanisms, and functional impact in patients. The research aims to better understand the aetiology and evolution of PLC symptoms to inform theoretical models and development of effective therapeutic interventions to improve patient care. Experimental measures include: advanced neuroimaging of brain circuitry, neuropsychological assessment, electromyography, transcranial magnetic stimulation.
For more information contact Sicong Tu E: sicong.tu@sydney.edu.au
Recent advances in both capacity and availability of high-performance computing has led to significant leaps forward in the development and application of deep learning models in science, in particular neuroimaging. Convolutional neural networks are increasingly being introduced into neuroimaging analysis pipelines to reduce processing time, enhance data quality, and improve classification accuracy. This research aims to develop and train deep neural networks for clinical application across neurodegenerative conditions, focusing on disease classification and prognosis. The research is being carried out in collaboration with the Computational Neuroscience Group.
For more information contact Sicong Tu E: sicong.tu@sydney.edu.au
This program of research operates as part of the collaborative efforts of the ForeFront Research Group. As part of a world-renowned research facility, we are involved in a multitude of evolving and innovative research projects. We are looking into a number of different techniques to predict and recognize neurodegenerative diseases years before they can currently be diagnosed. This includes developing tests for blood biomarkers, examining aspects of early gait dysfunction, improving techniques for brain imaging and examining changes to cognitive, visual and olfactory systems to name but a few. Additionally, we coordinate the NSW Movement Disorder Brain Donor Program, providing detailed clinical information to accompany valuable brain tissue that is utilized for research across Australia and the globe to improve our understanding of Parkinsonian syndromes. Finally, we are actively involved in a number of clinical trials targeting both symptomatic and disease modifying therapies for Parkinson’s disease. Most notably we form an integral component of the Australian Parkinson’s Mission, which funded by the federal government is seeking to establish a series of disease modifying trials incorporating novel genetic and blood-based biomarker approaches. Prof Simon Lewis is an NHMRC Leadership Fellow who has committed to work predicting, diagnosing and treating diseases like Parkinson's and Dementia with Lewy Bodies, along with their most troubling symptoms. This work will utilise genetics and biomarkers along with clinical trials, neuroimaging, neurophysiology and other approaches to improve our understanding of a range of problems including cognitive decline, hallucinations and freezing of gait.
Projects available:
Coming soon
Magnetic Resonance Imaging (MRI) remains the most reliable, clinically available and non-invasive method to measure brain changes in dementia during life, and can be used to acquire information about the structure and function of the brain. The Brain and Mind Centre MRI Research group combine neuroimaging techniques, clinical and molecular data to characterise individual differences in disease trajectories in dementia. This innovative approach is paramount to more accurate diagnosis, prognosis and the development of effective treatments to reduce the prevalence and associated costs of dementia.
Projects available:
Coming soon
How do distributed whole-brain neural activity patterns give rise to human cognitive function? This question lies at the heart of modern psychology and neuroscience but, despite decades of neuroimaging experiments, we still don’t have a clear answer. The Brain and Mind Functional Magnetic Resonance Imaging (fMRI) research group combines neuroimaging data with computational modelling in order to understand the complex, adaptive brain dynamics that form the basis of cognition and attention, and also how they begin to fail in dementia.
Projects available:
Coming soon
Our group comprises mathematicians/statisticians, IT engineers/computer scientists, and biologists/bioinformaticians at the Brain and Mind Centre, University of Sydney, specialized for development of bioinformatics & AI methodology to manage, analyze and mine large, complex datasets. The team’s contribution is the development of new methodology and the proof of concept on previously developed bioinformatics framework to process thousands of high-dimensional data sets in a time effective and coherent way.
Projects available:
Coming soon
Our biomarker team undertakes technical and scientific operations for the collection, preparation, archiving and analysis of blood and other biospecimen samples from patients for the development of biomarkers. The overall aim of the program is identify unique profiles of proteins, lipids, endogenous retroviruses and other molecular markers that can be measured and used to accurately distinguish different pathological forms of dementia from each other, particularly different types of frontotemporal temporal dementia, and other neurodegenerative diseases. At the same time, we conduct biochemical and pathological research to pinpoint and understand perturbed pathways underlying neurodegenerative diseases.
Projects available:
Coming soon
Read more about the Brain and Mind Centre.
The Dementia Research Centre is a multidisciplinary team within the Department of Biomedical Sciences and the Faculty of Medicine, Health and Human Sciences in MQ Health. The DRC enables cutting edge discovery research with a focus on translating findings into treatment for patients. It is the first dementia research centre in New South Wales that is fully dedicated to discovery-based research and drug development for dementia.
ForeFront have two main laboratory-research programs based at the Dementia Research Centre.
More information on the DRC Frontotemporal dementia, dementia and animal models research group coming soon.
Projects available:
The Dementia Research Centre (DRC) is offering a 3-year PhD-stipend to investigate the physiological role of long non-coding RNAs (lncRNAs) expressed in the brain. Using the latest CRISPR genome editing technologies, this project will provide new knowledge in the field by generating and analysing new mouse models of centrally expressed lncRNAs in order to better understand the contribution of lncRNAs to health and disease. The multidisciplinary research program of the Dementia Research Centre at Macquarie University provides ample opportunities to learn and apply cutting-edge technologies to decipher mechanisms in brain functions and diseases.
For more information visit the Macquarie University Research page
More information on the DRC Motor Neurone Disease research group coming soon.
Projects available:
Coming soon
Macquarie has assembled the largest research centre in Australia that is focused solely on finding the causes of MND and developing therapies to cure it.
Dominic Rowe is a chief investigator of the ForeFront research group, and runs clinical trials at the centre. For more information on the clinical trials email clinicaltrials@mq.edu.au
Ian Blair, co-director and Genetics and Genomics group leader and some of research team work collaboratively with the ForeFront group in seeking to understand the molecular origins of MND and developing new treatments for evaluation through clinical trials.
More information on the Genetics research group coming soon.
Projects available:
Coming soon