I use multidisciplinary and neuroimaging approaches to understand how the biochemistry of the brain affects how the brain functions in health and disease. This basic science underpins treatment approaches and furthers our understanding of a wide range of brain disorders.
Are Oligodendrocytes The Missing Link In Amyotrophic Lateral Sclerosis Pathogenesis?
Funder
National Health and Medical Research Council
Funding Amount
$1,054,405.00
Summary
Amyotrophic Lateral Sclerosis (ALS) is a debilitating and progressive neurodegenerative disease. Recent research suggests important cells of the central nervous system called glia play a role in disease onset and progression. We are interested in a type of glia called oligodendrocytes; they are crucial for supporting the survival of the cells that die in ALS. Only through understanding the underlying biology of ALS can we aim to identify effective therapies that will benefit patients.
Mechanisms Of A Novel Strategy For Neuroprotection In Experimental Models Of Stroke And Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$480,499.00
Summary
Stroke and epilepsy are among the most common neurological disorders affecting many Australians. In both disorders, brain metabolism is disturbed. Dr. Borges has found that an edible oil inhibits seizures in mice and it is now being tested in epilepsy patients. This grant will allow her laboratory to study the effects of this oil against stroke and to investigate how it protects the brain. New knowledge obtained will help to develop new treatments for brain disorders.
The Interactive Effects Of Dietary Saturated Fat And Apolipoprotein-E Genotype On Peripheral Metabolism Of Lipoprotein-amyloid And Neurovascular Integrity.
Funder
National Health and Medical Research Council
Funding Amount
$637,536.00
Summary
This project is based on a remarkable discovery which suggests that in some individuals, Alzheimer's disease may be a consequence of corruption of microscopic blood vessels that supply brain, damaged as a consequence of exaggerated exposure in blood to a protein produced principally in liver. The project will explore this pathway further in subjects at heightened risk of Alzheimer's disease and in humanised animal models. The findings may provide new opportunities for prevention and treatment.
The Role Of Liver Fructose-1,6-phosphatase (FBPase) In Body Weight Regulation
Funder
National Health and Medical Research Council
Funding Amount
$494,718.00
Summary
We have shown that fructose-1,6-bisphosphatase (FBPase), an enzyme important in producing sugar from the liver and one that is connected to Type 2 diabetes, does not cause an increase in sugar production when there is more of the enzyme in mouse livers. It does, however, lower both body weight and the amount of food the mice consume. We therefore hypothesise that liver FBPase is important in controlling body weight in humans and our project aims to find out exactly how and why this happens.
Characterisation Of A New Family Of Proteins Involved In Cell Signalling, RNA Metabolism And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$200,880.00
Summary
We have discovered a novel RNA-binding protein (G3BP-2) that is involved in responding to external signals, such as growth factors, at the level of gene expression. Other RNA-binding proteins belonging to the same broad group of proteins are responsible for a host of disease states in mammals including mental retardation, myotonic dystrophy, Huntington?s disease and cancers. Considering the wealth of knowledge accumulated that implicates these proteins to human dysfunction surprisingly few of th ....We have discovered a novel RNA-binding protein (G3BP-2) that is involved in responding to external signals, such as growth factors, at the level of gene expression. Other RNA-binding proteins belonging to the same broad group of proteins are responsible for a host of disease states in mammals including mental retardation, myotonic dystrophy, Huntington?s disease and cancers. Considering the wealth of knowledge accumulated that implicates these proteins to human dysfunction surprisingly few of these RNA-binding proteins have been identified. We have shown that the novel protein discovered in our laboratory is perturbed in cancer and we are interested in characterising its putative role in cancer. The results established in our laboratory so far would indicate that generally, G3BP-2 is expressed in normal tissue and it expression changes in some cancers studied so far. Considering that G3BP-2 lies in a pathway known to be involved in cancer progression it is important to understand what effects the inappropriate expression of G3BP-2 may have on cancer progression and survival. This project is designed to characterise what signals the cell uses to control these proteins and in turn which genes these may effect. In this way we may be able to determine how external signals may effect tumour progression and on what genes this influence is expressed. It would be hoped that this project would increase our understanding of cancer and potentially lead to new diagnostic reagents and therapies in the treatment of cancer.Read moreRead less
Structural And Functional Studies On Glutamate Decarboxylase.
Funder
National Health and Medical Research Council
Funding Amount
$500,460.00
Summary
This proposal aims to determine the molecular structure of the two known isoforms of Glutamate Decarboxylase (GAD65 and GAD67). GAD in an essential human enzyme that is responsible for synthesising the primary inhibitory neurotransmitter gamma-aminobutyric acid (GABA). GABA functions in the human Central Nervous System (CNS) to dampen down excitatory signals. Proper control of GABA synthesis is important and perturbations in GABA levels lies behind human diseases such as intractable epilepsy, de ....This proposal aims to determine the molecular structure of the two known isoforms of Glutamate Decarboxylase (GAD65 and GAD67). GAD in an essential human enzyme that is responsible for synthesising the primary inhibitory neurotransmitter gamma-aminobutyric acid (GABA). GABA functions in the human Central Nervous System (CNS) to dampen down excitatory signals. Proper control of GABA synthesis is important and perturbations in GABA levels lies behind human diseases such as intractable epilepsy, depression and schizophrenia. As a result of this role, numerous common therapeutics (for example benzodiazepines) target proteins involved in the GABA neurotransmitter system. The goal of this proposal is to use the molecular structures of GAD to understand how to achieve fine control of GABA production. In addition to its role in the CNS, GAD is an important human autoantigen. Antibodies to one isoform of GAD, GAD65, are found in most patients with type I diabetes as well as certain patients with the movement disorder stiff person syndrome and related diseases of the CNS. It is suggested that the development of auto-antibodies may play a key role in the pathophysiology of these conditions. Despite sharing >80% sequence similarity with GAD65, autoantibodies to the other isoform of GAD, GAD67, are rarely found in patients with disease. The aim of this grant is to characterise the region of GAD that is targetted by autoantibodes. These data will allow us to understand why certain autoantibodes are able to inhibit GAD enzyme activity and why GAD65, but not GAD67 is recognised by autoantibodes.Read moreRead less