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Elucidating The Pathological Role And Predictive Value Of Mental Health Disorder Risk Genes
Funder
National Health and Medical Research Council
Funding Amount
$1,562,250.00
Summary
Mental health disorders such as schizophrenia and depression are common and often debilitating conditions. The genes in our DNA play a large role in who develops these disorders and many risk genes have been identified. We will investigate when and how these risk genes are “switched on” to work out how they cause disease and to accurately predict who is at high risk of developing a mental health disorder. These advances will help us to understand disease causation and to improve treatments.
A Convergent Approach To Define The Behavioural And Pathophysiological Signatures Of Neuropsychiatric Symptoms
Funder
National Health and Medical Research Council
Funding Amount
$350,889.00
Summary
Most people with Parkinson’s disease (PD) will experience neuropsychiatric symptoms. Currently, these complex symptoms are poorly understood and treatment options are limited. My project will use psychological tests, neuroimaging and pharmacological investigations, to identify the specific brain changes leading to neuropsychiatric symptoms. My goal is to advance our understanding of what causes these symptoms, so that we can develop effective treatments and improve quality of life in PD.
Advanced Paternal Age: Behavioural, Neuroanatomical And Genomic Correlates In The Offspring Of Older Fathers
Funder
National Health and Medical Research Council
Funding Amount
$501,565.00
Summary
The offspring of older fathers have an increased risk of developing disorders such as autism and schizophrenia. This is thought to be due to mutations in the developing sperm. Our group has shown in a mouse model that the offspring of older fathers have changes in brain shape and in behaviour, similar to some findings in autism. In this grant we will refine this animal model and explore the brain, behavioural and genetic correlates of advanced paternal age.
Optimising Current Therapeutic Approaches To Schizophrenia: The OPTiMiSE Consortium
Funder
National Health and Medical Research Council
Funding Amount
$1,016,659.00
Summary
Despite modern treatments advances (medications and psychological treatments), the prognosis of schizophrenia has only improved marginally and is individually variable. The OPTiMiSE Consortium, consisting of leading experts in schizophrenia research across Europe and a group in Australia, will commence a 5-year research program world-first in scale and scope. We will investigate the biological markers related to treatment response in over 1000 individuals with recent-onset schizophrenia. Schizop ....Despite modern treatments advances (medications and psychological treatments), the prognosis of schizophrenia has only improved marginally and is individually variable. The OPTiMiSE Consortium, consisting of leading experts in schizophrenia research across Europe and a group in Australia, will commence a 5-year research program world-first in scale and scope. We will investigate the biological markers related to treatment response in over 1000 individuals with recent-onset schizophrenia. Schizophrenia is a chronic disease and despite modern medication and psychological treatments the outcome is highly variable and often poor. The Melbourne Neuropsychiatry Centre is part of the European based OPTiMiSE Consortium, the largest ever research program evaluating why individuals with schizophrenia vary in response to different medications. We will examine what characteristics predict which drugs are most helpful to 120 individuals with first episode schizophreniaRead moreRead less
NeuroSleep: The Centre For Translational Sleep And Circadian Neurobiology
Funder
National Health and Medical Research Council
Funding Amount
$2,659,061.00
Summary
NeuroSleep, the Centre for Translational Sleep and Circadian Neurobiology, will foster innovative clinical research and translation to develop national capacity in understanding how sleep disorders and dysfunction of the body clock impact on health. The Centre will focus its activities on the two-way relationship between disrupted sleep and body clock systems and brain disorders. Our goal is to improve brain performance, workplace safety and health outcomes in patients with sleep and circadian d ....NeuroSleep, the Centre for Translational Sleep and Circadian Neurobiology, will foster innovative clinical research and translation to develop national capacity in understanding how sleep disorders and dysfunction of the body clock impact on health. The Centre will focus its activities on the two-way relationship between disrupted sleep and body clock systems and brain disorders. Our goal is to improve brain performance, workplace safety and health outcomes in patients with sleep and circadian dysfunction and in the general community.Read moreRead less
THE EFFECTS OF TRANSCRANIAL MAGNETIC STIMULATION (TMS) ON RAT MODELS OF DEPRESSION
Funder
National Health and Medical Research Council
Funding Amount
$204,274.00
Summary
Repetitive Transcranial Magnetic Stimulation (rTMS) is the direct stimulation of the brain by using high field magnetic pulses. It is a new technique that has been demonstrated to have some potential as a treatment of depressive illness and possibly other neuropsychiatric disorders. At this early stage of its investigation, the parameters of stimulation that are most likely to be therapeutic, and its mechanisms of action, are not known. Published studies vary in the frequency, duration and exten ....Repetitive Transcranial Magnetic Stimulation (rTMS) is the direct stimulation of the brain by using high field magnetic pulses. It is a new technique that has been demonstrated to have some potential as a treatment of depressive illness and possibly other neuropsychiatric disorders. At this early stage of its investigation, the parameters of stimulation that are most likely to be therapeutic, and its mechanisms of action, are not known. Published studies vary in the frequency, duration and extent of stimulation, with no firm guidelines about optimal parameters. Empirical study of the relative effects of stimulation at different frequencies, at different numbers of stimuli and for different durations is therefore important for the future development of this treatment. Such an investigation is best carried out in an animal model of depression for both ethical and practical reasons, as such studies in patients would possibly take many years and be extremely difficult to conduct. We propose such a study in rat models of depression which have demonstrated validity and utility in drug research. Rat models have a long track record in developing psychiatric treatments and are cost-effective and of proven value. We also plan to investigate the neuroanatomy of the immediate-early genes induced by TMS and compare it with electroconvulsive shock (ECS) and a tricyclic antidepressant, two established treatments of depression. The results will have implications for future human studies in guiding us toward the optimal parameters for therapeutic effects. They will also enhance our understanding of the mechanism of action of TMS in depression.Read moreRead less
Life Course Trajectories And Neuropsychiatric Outcomes In An E-cohort Of High Risk Children Of Mothers With Psychosis
Funder
National Health and Medical Research Council
Funding Amount
$796,484.00
Summary
This study investigates how genetic and environment factors operate over the life course to increase risk of adverse outcomes for children of women with severe mental illness. We examine the clustering of neuropsychiatric outcomes in families and individuals, the role of developmental adverse life events in the risk for these outcomes, and the children's physical morbidity and offending profiles. This is an electronic cohort (e-cohort), constructed by record linkage across many databases.
Understanding The Molecular Basis Of Bipolar Affective Disorder
Funder
National Health and Medical Research Council
Funding Amount
$812,250.00
Summary
Bipolar disorder (manic depressive illness) is a severe mood disorder, with a lifetime prevalence of up to 1.6%. The illness is characterised by aberrant mood swings resulting in periods of mania and depression with reversion to normal behaviour between episodes. The condition has a severe impact on sufferers, being demonstrated to be the sixth most disabling disorder in the WHO Global Burden of Disease report and increasing the risk of suicide fifteen-fold. There is a pressing need to define mo ....Bipolar disorder (manic depressive illness) is a severe mood disorder, with a lifetime prevalence of up to 1.6%. The illness is characterised by aberrant mood swings resulting in periods of mania and depression with reversion to normal behaviour between episodes. The condition has a severe impact on sufferers, being demonstrated to be the sixth most disabling disorder in the WHO Global Burden of Disease report and increasing the risk of suicide fifteen-fold. There is a pressing need to define more clearly the biological basis of bipolar disorder as a necessary prerequisite to improved diagnosis and treatment. The underlying causes of bipolar disorder remain unknown. However, family studies reveal the high heritability of bipolar disorder and this familial clustering provides an opportunity to use genetic approaches to identify the predisposing genes. The long-term aim of our research is to investigate the biology of those genes that either cause or predispose to bipolar disorder. We have previously reported strong evidence for a novel bipolar disorder susceptibility gene on chromosome 4, a finding which has subsequently been reproduced in several independent studies. Consequently, we hypothesise that there is a gene located on chromosome 4 that predisposes to bipolar disorder. The aim of this proposal is to identify the chromosome 4 bipolar susceptibility gene and understand how the gene causes bipolar disorder. Identifying the genes responsible for bipolar disorder will allow us to define and understand the biological basis of this severe psychiatric condition. This will ultimately lead to major improvements in the ability to diagnose, treat and prevent the illness.Read moreRead less
Interaction Of Oestrogen With The Serotonin-1A Receptor: Implications For Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$229,744.00
Summary
Gender differences have been observed in mental illnesses such as schizophrenia. It has been suggested that the female sex hormone, oestrogen, protects against schizophrenia, although how this occurs is unclear. This project aims to understand the mechanisms by which oestrogen interacts in the brain with major chemical systems (including serotonin and dopamine) that are implicated in the development and symptoms of schizophrenia.
G Protein-Coupled Receptors (GPCRs) form the largest family of receptors and drug targets in living organisms. Currently, the major reason that new drugs fail to reach the clinic is lack of appropriate drug effect (approx. 30%). Thus, we need a better understanding of how GPCRs work and how this relates to disease. Work within my fellowship will address this knowledge gap, using GPCR models that are relevant to treatment of metabolic, inflammatory, cardiovascular and central nervous system disea ....G Protein-Coupled Receptors (GPCRs) form the largest family of receptors and drug targets in living organisms. Currently, the major reason that new drugs fail to reach the clinic is lack of appropriate drug effect (approx. 30%). Thus, we need a better understanding of how GPCRs work and how this relates to disease. Work within my fellowship will address this knowledge gap, using GPCR models that are relevant to treatment of metabolic, inflammatory, cardiovascular and central nervous system disease.Read moreRead less