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
Aurora Kinase: Molecular, Cellular And Functional Studies Deciphering Its Role In Stroke Injury
Funder
National Health and Medical Research Council
Funding Amount
$580,993.00
Summary
In stroke patients, oxygen deprivation indirectly induces massive nerve cell death by activating an enzyme called aurora kinase A (AURKA). We aim at unravelling (i) how AURKA is activated by oxygen deprivation, (ii) where the activated AURKA is localised in cells, and (iii) how the activated AURKA induces nerve cell death.The study will benefit development of therapeutic strategies to protect against brain damage in stroke since this is novel and different target for drug targeting.
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.
Viral Infection And TGFbeta Impair Glucocorticoid Activity In Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$617,699.00
Summary
Chronic inflammatory lung diseases like asthma and smokers lung are treated with combinations of anti-inflammatory drugs. Powerful anti-inflammatory types of steroid drugs are used in more severe disease. Even these powerful drugs are sometimes not effective enough. Our work is developing an understanding of how inflammation limits the anti-inflammatory effects of steroids and we are devising ways to overcome this with new drugs. We aim to improve treatment of chronic inflammatory diseases, espe ....Chronic inflammatory lung diseases like asthma and smokers lung are treated with combinations of anti-inflammatory drugs. Powerful anti-inflammatory types of steroid drugs are used in more severe disease. Even these powerful drugs are sometimes not effective enough. Our work is developing an understanding of how inflammation limits the anti-inflammatory effects of steroids and we are devising ways to overcome this with new drugs. We aim to improve treatment of chronic inflammatory diseases, especially those affecting the lung.Read moreRead less
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.
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.
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
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.
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.
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.