A Breakdown Of Cortical Homeostasis In Depression: A Focus On The Anterior Cingulate
Funder
National Health and Medical Research Council
Funding Amount
$625,629.00
Summary
Major depressive disorders affect 20% of the Australian population. Some symptoms of major depressive disorders arise because of a dysfunction of the human brain, particularly the cortex. Our studies show there are biochemical changes in the anterior cingulate cortex in people with mood disorders. We will now extend our studies to show there is a breakdown in the balance between neurotransmitter and neuroinflammation pathways in the anterior cingulate cortex in major depressive disorders.
Rational Co-targeting Of G Protein-coupled Receptors As A Novel Approach Towards Treating Neuropsychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$620,399.00
Summary
Schizophrenia is a common mental disorder with multiple symptoms. Current therapeutics only treat some of these symptoms. This project will focus on two important brain proteins implicated in schizophrenia. With the hypothesis that the rational targeting of these two proteins will lead to the design of more effective medicines for treatment of schizophrenia we will develop novel methods to selectively and simultaneously and target these two proteins.
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.
Antibody-based Inhibition Of ADAM10 As Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$652,788.00
Summary
Despite our advances in understanding the molecular basis of cancer, treatments for metastatic cancers are limited, emphasising an urgent need for strategies targeting several oncogenic pathways. We generated monoclonal antibodies effectively blocking the activity of ADAM10, an oncogenic cell surface protease that activates tumour growth, invasion and metastasis through multiple pathways. Here we describe the strategies that progress these antibodies as lead therapeutics for clinical testing.
Understanding Novel Drug Binding Pockets At G Protein-coupled Receptors
Funder
National Health and Medical Research Council
Funding Amount
$425,538.00
Summary
Cell-surface proteins exhibit multiple secondary binding sites for which only synthetic drugs have been identified so far. My hypothesis is that these secondary binding sites are common to most proteins because they are primarily targeted by largely yet unidentified endogenously released molecules that can modify the biology of these proteins.
Spatial And Temporal Dimensions Of Mu-opioid Receptor Signalling: Implications For The Development Of Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$799,316.00
Summary
The use of morphine as an analgesic is still limited by undesirable side effects such as tolerance. Despite decades of research, the mechanisms behind the development of tolerance are poorly understood. The ? opioid receptor is a protein expressed at the surface of the cells that is the target of morphine. This project will investigate the signalling events triggered by opioids with unprecedented resolution and will aim to elucidate why morphine elicits more tolerance than other opioid drugs.
Adenosine Receptor Biased Agonism To Treat Ischaemic Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$682,163.00
Summary
Adenosine A1 receptor (A1R) activation confers powerful protection to heart cells, however clinical application remains suboptimal due to adverse effects such as a slowing in heart rate and decrease in blood pressure. Importantly a new class of compounds, A1R biased agonists, can mediate potent cardioprotection in the absence of adverse effects. This proposal will establish the molecular mechanisms involved and the scope to develop A1R biased agonists as a novel approach to treat heart disease.
Adenosine Receptor Context-Specific Biased Agonism To Treat Ischaemic Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,021,744.00
Summary
Heart attacks and secondary heart failure remain significant health burdens. Stimulation of adenosine receptors located on heart cells confers powerful cardiac protection, improving acute and longer-term heart function subsequent to a heart attack but avoiding the usual unwanted effects from this approach. We aim to better understand the mechanism of action of potential adenosine receptor therapeutics and establish the clinical potential of these compounds using animal models of heart failure.
Understanding Mechanisms Of Allostery And Biased Agonism At The Adenosine A1 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$603,033.00
Summary
This project focuses on an important protein found in the heart. Drugs that activate this protein can protect the heart against damage that occurs after a heart attack, but they all have undesirable side effects. We have discovered a new class of molecule that can protect the heart without these side effects. We now seek to understand how these compounds work at the molecular level. This knowledge can facilitate the design of safer medicines for the treatment of cardiovascular disease.
Molecular Determinants Of Drug Binding And Selectivity At Muscarinic Acetylcholine Receptors
Funder
National Health and Medical Research Council
Funding Amount
$816,866.00
Summary
G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors in the human genome, and drugs targeting these receptors account for 30% of marketed drugs. This project aims to determine high resolution structural information on how drugs bind and specifically interact with GPCRs, which will enable future development of selective and effective drugs.