The Importance Of Receptor Trafficking For Signalling Of Pain And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$787,604.00
Summary
Inflammation and pain are normal processes that are essential for survival: inflammation fights infections and pain allows avoidance of danger. These processes are normally tightly controlled and are transient. During disease, they become dysregulated and chronic. By understanding the normal processes of inflammation and pain, and by determining how dysregulation causes disease, we aim to develop new treatments for diseases that are a major cause of human suffering.
Irritable Bowel Syndrome (IBS) is one of the leading causes of chronic pain both world-wide and in Australia for which there is a lack of treatments. Chronic pain arises from nerve fibres in the colon wall, which fail to 'reset' back to normal following inflammation. Targeting these nerve endings with drugs is a key advance in IBS treatment. This project will identify selective oxytocin analogues that act in the colon to lower pain in sensory nerves thus providing efficacious pain relief in IBS.
Neuropathic pain is particularly difficult to treat and existing medications have considerable side effects. This project will develop a new set of glycine transport inhibitors that have the potential to provide pain relief without side effects.
Molecular Targets Of Amino Acid/neurotransmitter Conjugates Of Fatty Acids
Funder
National Health and Medical Research Council
Funding Amount
$846,390.00
Summary
This project investigates endogenous chemicals that affect cells important for detecting and responding to pain. We aim to discover how these compounds affect proteins important for nerve cell function, particularly proteins that have a prominent role in detecting and transmitting painful events. The compounds we examine are not themselves likely to be drugs, but future therapies may involve manipulating the levels of these chemicals in the body, or using drugs that mimic the activity of these c ....This project investigates endogenous chemicals that affect cells important for detecting and responding to pain. We aim to discover how these compounds affect proteins important for nerve cell function, particularly proteins that have a prominent role in detecting and transmitting painful events. The compounds we examine are not themselves likely to be drugs, but future therapies may involve manipulating the levels of these chemicals in the body, or using drugs that mimic the activity of these compounds.Read moreRead less
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.
Understanding The Physiological Consequences Of Biased Signalling Mediated By The Glucagon-like Peptide-1 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$636,508.00
Summary
The glucagon-like peptide 1 receptor is a major target for treatment of Type 2 diabetes and obesity. However, the development of drugs targeting this receptor is challenging as activation by different ligands can result in distinct signalling biases, a paradigm for which there is limited understanding of the physiological consequences. This project will address this critical knowledge gap and may allow for development of novel drugs with improved therapeutic outcomes.
Pharmacological Targeting Of Integrated Oncogenic And Tumour Suppressive Pathways Using Novel Therapeutics.
Funder
National Health and Medical Research Council
Funding Amount
$510,953.00
Summary
We will investigate NDRG1, a novel molecular target that has been demonstrated to inhibit the progression of numerous cancers. We aim to better understand the underlying function of NDRG1 in pancreatic cancer and how we can potentially target this gene with novel therapeutics being developed in our lab. We hope that this new approach will lead to promising treatments and a better outcome for those suffering from pancreatic cancer.
Identification Of Novel Targets For Treatment Of Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$486,873.00
Summary
Hearts respond to stimulation by activation of cell surface receptors. We have found that two very closely related receptors have opposing effects on the heart; one is beneficial and the other promotes disease. The planned studies will investigate exactly what explains this difference. This will identify critical factors that protect or damage the heart and is expected to provide suitable targets for drug development.
Glycine Transport Inhibitors For The Treatment Of Pain
Funder
National Health and Medical Research Council
Funding Amount
$923,660.00
Summary
Chronic pain is particularly difficult to treat. Whilst currently used opioid drugs are effective in acute pain, they are either ineffective in chronic pain or have considerable side effects. In this project we will develop a new class of analgesics that have a different mechanism of action to traditional analgesics. It is hoped that these new drugs will provide long term pain relief without debilitating side effects.
Novel Analgesic Approaches: Harnessing Functional Interactions Between Sodium Channels And Opioids
Funder
National Health and Medical Research Council
Funding Amount
$329,076.00
Summary
Chronic pain is a debilitating condition that affects the life of one five Australians and has significant socioeconomic impact. Currently available pain killers often do not work, or have intolerable side effects. We have discovered that combination treatment with opioids and a novel venom-derived compound discovered by us provides effective pain relief. The aim of this project is to understand the mechanisms underlying this synergistic effect to develop new treatment approaches for pain.