The Biological Role Of The Cadherin Gene FAT In Bipolar Disorder Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$509,491.00
Summary
Bipolar disorder (manic depressive illness) is a severe mood disorder, with a lifetime prevalence of up to 1%. 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 ....Bipolar disorder (manic depressive illness) is a severe mood disorder, with a lifetime prevalence of up to 1%. 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 used genetic approaches to identify the first bipolar disorder susceptibility gene, a cell contact molecule located on chromosome 4 that is from the cadherin family. The aim of this proposal is to understand how this gene contributes to the risk of developing bipolar disorder. This will be achieved by identifying how the cadherin susceptibility gene, termed 'FAT' results in altered properties in laboratory assays or in altered behaviours in animal models. Identifying the genes responsible for bipolar disorder and understanding their contribution to the biological basis of this severe psychiatric condition is essential to translate these discoveries into improvements in the ability to diagnose, treat and prevent the illness.Read moreRead less
Pathogenesis And Therapeutic Modulation Of Aggressive Behaviour In A Mouse Model Of Autism Spectrum Disorder
Funder
National Health and Medical Research Council
Funding Amount
$583,015.00
Summary
This project focuses on understanding the causes of aggressive behaviour in mice that have a human gene mutation found in autism. Aggressive behaviour is common in autism patients and can have severe consequences on education and employment opportunities. These mice also show excess dampening of brain function (inhibition). This project will test if aggression in these mice is caused by altered inhibition.
Gene-environment Interactions Modulating Cortical And Cognitive Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$618,300.00
Summary
A feature of many major brain disorders, including schizophrenia and dementia, is disruption of cognition. A key brain area impacted in such cognitive disorders is the prefrontal cortex. This project will use clinically translatable touchscreen to understand how this aspect of brain dysfunction causes abnormal cognition. We will investigate the mechanisms involved, using highly innovative approaches, which will contribute to the development of new treatments for such cognitive disorders.
Characterisation Of Eurl, A Novel Gene Implicated In The Etiology Of Abnormal Brain Development And Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$597,541.00
Summary
Intellectual disability affects around one per cent of Australians, and can arise from genetic abnormalities during fetal life, such as through abnormal regulation of gene expression. We have identified a novel gene, known as eurl, which controls brain assembly as well as the ability of neurons to form functional connections within the brain. We will investigate how this novel gene controls brain development, and characterise eurl as a potential therapeutic target for learning and memory.
Understanding the contribution of neuroinflammation in acute and chronic neural injury. A major focus of this project will be investigating the involvement of neuroinflammation in neural cell damage. It will explore how neuroinflammation contributes to this damage in both acute and chronic neuropathologies.
Regulation of neuronal cell death signalling for the treatment of neurodegenerative diseases. The progression of neurodegenerative diseases, such as Alzheimer's and motor neuron diseases, are often underpinned by neuronal cell death-signalling. This project aims to characterise molecules that regulate cell death signalling, thereby increasing our knowledge of how neuronal cell death can be inhibited.
Molecular And Cellular Mechanisms Of Axon Guidance In The Vertebrate Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$330,735.00
Summary
There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can ....There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can be used to assist in trying to modulate and facilitate directed regrowth following injury.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130100323
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The regulation by transcription factor phosphorylation upon the myelinating process. The project will investigate the novel molecular events that control the myelinating process, which is essential for normal nervous system function. Outcomes of this project may aid the development of novel interventions to improve control of demyelinating diseases, which represent a substantial socio-economic burden.
Investigating the neuroprotective actions of metallo-complexes. Metal-based drugs offer an exciting new approach to treatment of neurodegeneration. However, little is known about how cells metabolise these drugs: information that is critical for further drug development. This project will determine how metal-based drugs are metabolized by neuronal cells and how this may result in therapeutic benefit.