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Substance abuse is a significant social and economic burden upon Australian societies and on societies around the world. Treatment remains problematic due to the multi-layer nature of the disease, difficulties with treatment compliance and less than ideal treatment regimes. The present study aims to improve treatments for alcohol and drug abuse using pre-clinical models to identify and characterize a new brain system implicated in drug-seeking.
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.
Chronic inflammation underlies common and debilitating diseases and causes pain by unknown mechanisms. There is an urgent need to gain a deeper understanding of the mechanisms of chronic pain, which will allow the development of improved therapies with fewer side-effects. Our research program investigates the mechanisms of pain that are associated with inflammatory bowel disease and irritable bowel syndrome, with the goal of developing more effective and selective therapies.
Understanding The Function And Regulation Of G Protein-coupled Receptor Signalosomes And Their Role As High Resolution Signalling Platforms
Funder
National Health and Medical Research Council
Funding Amount
$566,588.00
Summary
G protein-coupled receptors are specialised proteins located on the surface of cells. They are the targets of 50% of currently available pharmaceuticals, but these drugs are derived from limited knowledge of only a fraction of proteins. This proposal will examine exciting and novel properties of receptors that only occur following the assembly of the proteins into specialised networks within cells. The new information will expand our current knowledge, and facilitate future targeted drug design.
Is Abdominal Discomfort A “colonic Itch”? Identification Of Itch Specific Pathways In The Gut In Health And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$906,996.00
Summary
Chronic abdominal pain is a major worldwide problem. TGR5 and Mrgpr receptors are expressed by neuronal pathways innervating the skin, where they detect irritants and transmit itch. Our novel, innovative project shows a similar pathway exists within the viscera, which plays a major and unappreciated role in chronic abdominal pain. These receptors represent novel targets for therapeutic treatment, potentially creating multibillion-dollar savings to the Australian economy and healthcare systems.
GABA(B) Receptor Modulation Of Gastrointestinal Function In Health And Disease By Alpha-Conotoxins
Funder
National Health and Medical Research Council
Funding Amount
$689,050.00
Summary
Chronic visceral pain is a common and debilitating condition arising from numerous diseases that affect our internal organs. There is a desperate need for more information about the mechanisms responsible for signalling chronic visceral pain to provide therapies and potentially find a cure for it. Our research focuses on ?-conotoxins (small peptides from marine cone snail venom) as novel potential therapeutic agents for the treatment of chronic visceral pain.
Novel Approaches To Understanding Peptide G-protein-coupled Receptor Activation
Funder
National Health and Medical Research Council
Funding Amount
$665,043.00
Summary
G protein-coupled receptors (GPCRs) are proteins that exist on every human cell, where they sense, and respond to environmental stimuli. Because of their importance they are targeted by drugs to treat many diseases. However little is known about the molecular steps that underlie cellular responses upon drug binding and this has hindered new drug development. This project uses new technology to determine the complex pathway of GPCR activation upon drug binding which will aid new drug development.
G Protein-Coupled Receptors (GPCRs) form the largest family of receptors and drug targets in living organisms. Currently, the major reason that new drugs fail to reach the clinic is lack of appropriate drug effect (approx. 30%). Thus, we need a better understanding of how GPCRs work and how this relates to disease. Work within my fellowship will address this knowledge gap, using GPCR models that are relevant to treatment of metabolic, inflammatory, cardiovascular and central nervous system disea ....G Protein-Coupled Receptors (GPCRs) form the largest family of receptors and drug targets in living organisms. Currently, the major reason that new drugs fail to reach the clinic is lack of appropriate drug effect (approx. 30%). Thus, we need a better understanding of how GPCRs work and how this relates to disease. Work within my fellowship will address this knowledge gap, using GPCR models that are relevant to treatment of metabolic, inflammatory, cardiovascular and central nervous system disease.Read moreRead less
Unravelling The Binding And Activation Mechanism Of A Complex G Protein-coupled Receptor
Funder
National Health and Medical Research Council
Funding Amount
$1,041,638.00
Summary
The peptide hormone relaxin is currently in a Phase III trial for the treatment of heart failure. However the peptide is not a good drug as it can't be taken orally and is very expensive to produce. We will study the interaction of relaxin with its cell surface receptor and the mechanisms by which the receptor functions. The knowledge gained will aid in the design of smaller, more potent and orally active forms of relaxin for the treatment of heart failure
Resolving And Targeting The Complex Molecular Mechanisms Underlying GPCR Signalling
Funder
National Health and Medical Research Council
Funding Amount
$1,071,370.00
Summary
Receptors are located on the surface of all human cells to allow our cells to respond to their environment. Over 30% of prescription drugs act through particular receptors called GPCRs, however effective drugs without side effects are difficult to develop because we do not have a deep understanding of how GPCRs transmit complex signals. In this proposal we seek to resolve the atomic-level details of GPCR signalling to assist in the development of better drugs for a diverse range of diseases.