Dynamic Trafficking Of Amino Acid Transporters At Synapses And Their Role In Regulating Neurotransmission
Funder
National Health and Medical Research Council
Funding Amount
$421,219.00
Summary
Brain cells release chemical neurotransmitters to activate their neighbours. The most abundant neurotransmitter is glutamate, which mediates most of the communication in the brain. Following release, this neurotransmitter must be rapidly recycled to prevent levels being depleted and neurotransmission failing. The subject of this grant is to understand what molecules and pathways are used to recycle glutamate in the brain, and how its supply is controlled to sustain continual brain activation.
Anxiety and addiction are disorders with high co-morbidity that present a major worldwide public health concern. Treatment in both cases often involves an approach called extinction which helps to reduce the relapsing nature of these disorders. This grant is designed to examine the role of a specific protein in addiction and anxiety, by virtue of its involvement in the process of extinction.
Biased Allosteric Modulators Of Metabotropic Glutamate Receptors: Novel Therapeutic Targets For CNS Disorders
Funder
National Health and Medical Research Council
Funding Amount
$611,534.00
Summary
Metabotropic glutamate receptor 5 (mGlu5) is a major therapeutic target for depression and schizophrenia. The proposed studies will improve our understanding of how drug-like chemicals interact with mGlu5 and therefore change the activity of these receptors and in turn the activity of brain cells leading to therapeutic effectiveness. The research undertaken in this program will allow us to be smarter in developing new mGlu5 drugs that are both effective and have minimal side effects.
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.
The Effects Of Maternal Infection On Glutamate-related Behavioural, Electrophysiological And Neuropathological Measures Relevant To Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$533,136.00
Summary
There are two well known facts about schizophrenia: maternal infection increases the risk of a schizophrenia diagnosis in adulthood and certain drugs, such as PCP, that affect particular brain chemicals induce symptoms and brain changes in healthy individuals that are similar to schizophrenia. Here we bring these two facts together by attempting to develop a maternal infection model in rodents that mimics the brain changes seen in schizophrenia, thus opening up new options for treatment.
We will investigate changes in the retina secondary to disease process and try and modify them to allow a longer time frame for intervention. These changes (remodelling) are detrimental to visual function and the effectiveness of measures aimed at restoring vision, eg, bionic eye.
Improving Outcomes Of Evidence-based Behaviour Therapy For Paediatric Obsessive-compulsive Disorder: A Translational Efficacy Trial Of D-cycloserine Augmented Intensive Behaviour Therapy
Funder
National Health and Medical Research Council
Funding Amount
$292,915.00
Summary
Obsessive Compulsive Disorder (OCD) is a debilitating mental health condition in childhood, and sadly, only about 50% of children are diagnosis-free following our best treatments. This study will test an innovate and safe treatment alternative, involving combining evidence-based psychological treatment with a small dose of anti-tuberculosis drug, d-Cycloserine.
Chronic pain is a debilitating syndrome caused by damage to tissue and the nervous system, arising from trauma and disease. It is poorly served by current drugs. To identify novel more effective therapies we propose to examine the mechanisms underlying this syndrome. We have identified a novel protein which is involved in synaptic plasticity. We will examine its role the development of chronic pain at the cellular level and how it might be exploited for the treatment of chronic pain.
Investigating The Impact Of Coincident Modulation Of Adenosine And Glutamate Receptors On Neuronal Activity – Implications For CNS Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$648,447.00
Summary
Dementia in particular Alzheimer's disease, is one of the leading causes of death. There remains a need for new drugs to treat both symptoms and disease progression. Two receptors in the brain, the adenosine A1 (A1AR) and metabotropic glutamate 5 (mGlu5) are suggested to be promising new drug targets for dementia. In order to better develop drugs that target these receptors, we will develop a better understanding of activity of these receptors under conditions of health and disease.