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
Epigenetic Determination Of Neuronal Vulnerability And Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$617,857.00
Summary
Neurons are faced with diverse forms of stress everyday. Neural diseases exacerbate this stress, causing interference to genes that normally allow neurons to function correctly. As a result, neurons die, and severe loss can result in diseases such as dementia. We have discovered new molecular factors in neurons that insulate their genes from stress, thereby protecting neuron function and health. The proposed research will exploit these mechanisms to better protect neurons from disease.
Cracking The Epigenetic Code: Understanding The Mechanisms Of Memory Associated With Anxiety-related Disorders And Their Treatment
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
The primary goal of my research programme is to elucidate how the epigenome coordinates experience-dependent gene expression underlying associative learning and memory using paradigms relevant for understanding fear-related anxiety disorders. My research on DNA modifications and newly emerging findings in the realm of RNA biology is changing the way we think about gene-environment interactions, the broader impact of which will most certainly continue to be felt for years to come.
Regulation Of Glutamate Receptor Trafficking By The Calcium- And Lipid-binding Protein, Copine-6
Funder
National Health and Medical Research Council
Funding Amount
$548,690.00
Summary
Abnormal levels of cell surface receptors in neurons can lead to a variety of debilitating neurological disorders and neurodegenerative diseases. These levels are tightly regulated through the orchestrated movements of receptors from inside the neuron to the cell surface. In this project we will examine how the transport of cell surface receptors is regulated by an intracellular signalling molecule, called copine, which is important in both epilepsy and Alzheimer’s disease.
How Does Iron Accumulation Affect Parkinson’s Disease And What Controls It?
Funder
National Health and Medical Research Council
Funding Amount
$545,517.00
Summary
Currently there is no cure for Parkinson's disease, and although we have a number of treatments to manage the disease there is an urgent need for a further understanding of the disease process. This proposal will investigate the critical role that iron plays in the cause of neuronal cell death that results in Parkinson's disease, and will investigate methods for regulating metal levels in the brain.
The Role Of Membrane Phospholipids In Regenerative Axonal Fusion
Funder
National Health and Medical Research Council
Funding Amount
$571,950.00
Summary
Injuries to the nervous system can cause lifelong disabilities due to ineffective repair of the damaged nerve fibres. Our previous research has identified a highly efficient mechanism that occurs in nematode worms that allows severed nerves to fuse back together. We will now focus on understanding precisely how this mechanism works, and investigate its utility in repairing nerves that don’t normally utilise this repair mechanism.
I am a neuroscientist-biochemist-cell biologist determining the mechanisms by which lipids and lipid transporters regulate neurodegeneration and vascular disease. I have recently developed a prototype drug that shows promise as a novel therapeutic approach for Alzheimer's disease.
Astroglial Remodelling Of The Interhemispheric Midline Is Regulated By Deleted In Colorectal Cancer (DCC) Signalling And Is Required For Corpus Callosum Formation
Funder
National Health and Medical Research Council
Funding Amount
$669,400.00
Summary
The integration of information between the brain hemispheres occurs via a large bundle of connecting nerve fibres called the corpus callosum. People with a genetic mutation in DCC display mirror movement disorder and some have a severe brain defect where the corpus callosum fails to form, but at present we don’t understand the function of this gene. In this study we will investigate how DCC functions in early brain development to regulate corpus callosum formation and mirror movement disorder.
Isoform-dependent ApoE Processing By Human Induced Pluripotent Stem Cells. A Novel Pathway Linking APOE Genotype And Alzheimer’s Disease Risk.
Funder
National Health and Medical Research Council
Funding Amount
$429,495.00
Summary
We recently discovered that a protein called apoE is cleaved in the brain to generate a small fragment that may have neuroprotective properties. We also discovered that human induced pluripotent stem cell (iPSC)-derived neurons produce apoE fragments identical to those in the brain. We will now characterise iPSC apoE and assess its neuroprotective properties. This will resolve the basis for the association of apoE with AD risk and potentially provide a new target for AD treatment.
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.