The Putative Drug Metabolising Enzyme SULT4A1 Is A Sulfotransferase Inhibitor
Funder
National Health and Medical Research Council
Funding Amount
$467,851.00
Summary
The sulfotransferase SULT4A1 is a novel protein found predominantly in neurons but its function is unknown. This project will investigate the mechanisms that the body uses to regulate the levels of this protein and how it may interfere with other enzymes essential for metabolising hormones and neurotransmitters.
Role Of The Drug Metabolising Enzyme Arylamine N-acetyltransferase 1 In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$600,196.00
Summary
The current project will identify the molecular mechanism(s) that underpins the significant changes in phenotype seen in a range of human cancer cells. The expected outcomes will be to demonstrate that NAT1 is critical for the clearance of pABG in cancer cells. The results will be important in the context of understanding this family of intracellular enzymes and will change the current thinking on the function of the arylamine N-acetyltransferase in normal and cancer cells.
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.
Many drugs modulate the function of proteins imbedded in cell membranes. Extensive research has been undertaken to better understand drug interactions with these proteins to improve drug therapies, but there has been relatively little progress in understanding the role of the cell membrane. This project will investigate how the cell membrane influences protein function and then use this information to develop novel drugs for the treatment of neurological disorders.
UGT Enzymes In Chemotherapeutic Drug Metabolism: New Avenues To Improve Drug Response And Overcome Resistance
Funder
National Health and Medical Research Council
Funding Amount
$610,005.00
Summary
Tumours treated by chemotherapy often become resistant to the drugs, leading to relapse and reduced chance of survival. We will study one of the main pathways leading to drug resistance, which could lead to the development of new ways to overcome resistance and improve cancer treatment outcomes.
A Novel Metabolic Role For UDP Glycosyltransferase 8 (UGT8)
Funder
National Health and Medical Research Council
Funding Amount
$419,144.00
Summary
The UDP glycosyltransferases (UGTs) are a family of enzymes that remove drugs and toxins from the human body as well as control levels of naturally produced molecules such as bile acids and hormones. We found that a new member of this family called UGT8 processes bile acids in the kidney and intestine and can affect how bile acids act to regulate metabolism. Our studies uncover new roles for bile acids in liver, kidney and gut health and in metabolic disorders such as diabetes and obesity.
Translating Membrane Proteins Into Therapeutics; From Bedside To Bench
Funder
National Health and Medical Research Council
Funding Amount
$9,466,000.00
Summary
Membrane proteins are the principal gatekeepers for control of cellular response, with G protein-coupled receptors (GPCRs) the largest family of cell surface proteins. These proteins are critically important for pathophysiological control, and are a major target for drug discovery. Nonetheless drug attrition due to lack of clinical efficacy remains high. We are combining cell biology, clinical management and drug discovery science to enable more effective therapeutic translation.
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.
Targeting TRPV4 Activation Mechanisms To Reveal Novel Pain Therapies
Funder
National Health and Medical Research Council
Funding Amount
$580,938.00
Summary
Pain nerves sense painful chemical and physical stimuli, by opening protein "ion channels" which let small electric currents traverse the cell membrane. This pain signal is transmitted to the spinal cord and then the brain, where it is perceived as pain and elicits a reaction. But we don't know how the ion channels open. This project will investigate how receptors for painful substances open ion channels to cause pain. Understanding this mechanism will help us to make new drugs to treat pain.
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.