The Australian Research Data Commons (ARDC) invites you to participate in a short survey about your
interaction with the ARDC and use of our national research infrastructure and services. The survey will take
approximately 5 minutes and is anonymous. It’s open to anyone who uses our digital research infrastructure
services including Reasearch Link Australia.
We will use the information you provide to improve the national research infrastructure and services we
deliver and to report on user satisfaction to the Australian Government’s National Collaborative Research
Infrastructure Strategy (NCRIS) program.
Please take a few minutes to provide your input. The survey closes COB Friday 29 May 2026.
Complete the 5 min survey now by clicking on the link below.
Investigating the functional interaction between vasopressin and angiotensin receptors. Kidney disease resulting from diabetes is a major health issue for Australians, and indigenous Australians in particular. This project aims to enable improved therapies to be developed, as well as better inform doctors regarding the use of potential combinations of existing pharmaceuticals to treat this condition.
Probing UDP-glucuronosyltransferase Protein-protein Interactions: The Power Of Two.
Funder
National Health and Medical Research Council
Funding Amount
$482,710.00
Summary
Drugs and other chemicals (eg. dietary constituents, environmental pollutants, and chemicals that occur naturally in the body - such as steroid hormones) are broken down by specialised proteins called enzymes. This process is referred to as biotransformation, or 'metabolism'. Drug and chemical metabolism serves as a detoxification mechanism (since the products of metabolism generally lack biological activity) and as a means of eliminating these substances from the body. UDP-Glucuronosyltransfera ....Drugs and other chemicals (eg. dietary constituents, environmental pollutants, and chemicals that occur naturally in the body - such as steroid hormones) are broken down by specialised proteins called enzymes. This process is referred to as biotransformation, or 'metabolism'. Drug and chemical metabolism serves as a detoxification mechanism (since the products of metabolism generally lack biological activity) and as a means of eliminating these substances from the body. UDP-Glucuronosyltransferase (UGT) is one of the most important enzymes involved in drug and chemical metabolism. Consistent with its ability to metabolise such a large number of compounds, UGT is known to exist as a 'superfamily' of structurally related proteins. Despite the importance of UGT, little is known about the structural characteristics of these enzymes that are responsible for recognising and binding different classes of chemicals. Accumulating evidence from this and other laboratories indicates that the individual UGT proteins may combine with themselves (to form a homodimer) and with other UGT proteins (to form heterodimers). This project largely seeks to define the scope of UGT homo- and hetero- dimerisation, identify the structural elements of the proteins responsible for association and characterise the functional significance of dimerisation. The project will further explore associations between UGTs and other proteins, namely albumin. Characterisation of UGT dimerisation and associations with other proteins is fundamental to our understanding of how this enzyme functions and selects particular chemicals for metabolism. The work also has important implications for the devlopment and interpretation of in vitro (or 'test-tube') approaches for predicting how drugs are metabolised in humans. Such tests are widely employed in research and pharmaceutical company laboratories to predict how the body 'handles' new drugs prior to their administration to humans.Read moreRead less
Elucidation Of The Molecular Requirements Of The Low Affinity 'state' Of The Beta1-adrenoceptor
Funder
National Health and Medical Research Council
Funding Amount
$535,500.00
Summary
Beta-blockers are used for the management of cardiovascular diseases including heart failure, ischaemic heart disease and high blood pressure. Beta-blockers mostly work by blocking the effects of a naturally occuring chemical called noradrenaline. Beta-blockers can be used to prevent noradrenaline induced increases in the rate and force of human heart contraction. We have discovered that one group of beta-blockers exemplified by CGP 12177 has the remarkable property of not only being able to blo ....Beta-blockers are used for the management of cardiovascular diseases including heart failure, ischaemic heart disease and high blood pressure. Beta-blockers mostly work by blocking the effects of a naturally occuring chemical called noradrenaline. Beta-blockers can be used to prevent noradrenaline induced increases in the rate and force of human heart contraction. We have discovered that one group of beta-blockers exemplified by CGP 12177 has the remarkable property of not only being able to block beta-receptors but they can also stimulate them at higher concentrations. Thus low concentrations block the effects of noradrenaline, but higher concentrations stimulate the receptor. More puzzling is that the stimulant effects of this group of beta-blockers cannot be easily blocked. To explain this we hypothesize that human beta-receptors can exist in two different 'states'. One 'state' can be stimulated by noradrenaline and blocked by low concentrations of beta-blockers such as propranolol and CGP 12177. Another 'state' of the same receptor is resistant to blockade by beta-blockers such as propranolol but can be stimulated by beta-blockers such as CGP 12177. This project seeks to investigate the molecular basis of the beta-adrenoceptor that is responsible for stimulant effects of beta-blockers. Specifically it explores the components of the beta-adrenoceptor that are critically and uniquely important for interacting with the stimulant beta-blockers. This project is an important increment in our laboratories research program to increase our understanding of the effects of beta-blockers. Our long term goal is to be able to develop beta-blockers that can block both states of the beta-adrenoceptor to provide a more effective block of the receptor and in particular for the improved management of heart failure.Read moreRead less
Molecular Determinants Of UDP Glucuronosyltransferase 1A3 And 1A4 Expression
Funder
National Health and Medical Research Council
Funding Amount
$516,078.00
Summary
Enzymes in the liver and gastrointestinal tract have a crucial role in protecting against the toxic effects of fat-soluble chemicals. Two of these enzymes called UGT1A3 and UGT1A4 have a special role in protecting against drugs and toxins that contain nitrogen groups. The levels of these two enzymes in the liver and gut vary extensively between individuals. In this project we will determine how the levels of these enzymes are controlled and what is the cause of this variability between individua ....Enzymes in the liver and gastrointestinal tract have a crucial role in protecting against the toxic effects of fat-soluble chemicals. Two of these enzymes called UGT1A3 and UGT1A4 have a special role in protecting against drugs and toxins that contain nitrogen groups. The levels of these two enzymes in the liver and gut vary extensively between individuals. In this project we will determine how the levels of these enzymes are controlled and what is the cause of this variability between individuals. This will help us predict those individuals who are more at risk from the adverse effects of nitrogen-containing drugs and from the toxic effects of chemicals in the diet or the environment. This project will also help us develop methods to increase the levels of these protective enzymes and help reduce the effects of exposure to toxic chemicals.Read moreRead less
Bias and allostery at the calcium sensing receptor. This project aims to provide a mechanistic and dynamic picture of the structure, function and physiology of the human calcium sensing receptor (CaSR), which is critical for vertebrate life. By responding to chemicals in the body, it acts as a universal nutrient sensor to maintain extracellular calcium homeostasis and mediate biological functions, including neurotransmission, inflammation, digestion, blood pressure and development. However, it i ....Bias and allostery at the calcium sensing receptor. This project aims to provide a mechanistic and dynamic picture of the structure, function and physiology of the human calcium sensing receptor (CaSR), which is critical for vertebrate life. By responding to chemicals in the body, it acts as a universal nutrient sensor to maintain extracellular calcium homeostasis and mediate biological functions, including neurotransmission, inflammation, digestion, blood pressure and development. However, it is not known how this single receptor controls the actions of multiple ligands to mediate numerous functions. By elucidating the roles of the CaSR and its ligands, this project aims to better understand fundamental physiological processes.Read moreRead less
UDP Glucuronosyltransferases As Regulators Of Signaling Pathways Modulated By Chemical Ligands.
Funder
National Health and Medical Research Council
Funding Amount
$500,460.00
Summary
Cells respond to their surroundings by transferring information received at the cell surface to the nucleus leading to changes in gene expression. There are many signaling pathways which transfer this informatrion to the nucleus. Some of these pathways are controlled by small molecules, usually fat-soluble chemicals. As a family of enzymes, the UDP glucuronosyltransferases (UGT) have evolved to eliminate fat-soluble chemicals, we propose that UGTs play a pivotal role in regulating the concentrat ....Cells respond to their surroundings by transferring information received at the cell surface to the nucleus leading to changes in gene expression. There are many signaling pathways which transfer this informatrion to the nucleus. Some of these pathways are controlled by small molecules, usually fat-soluble chemicals. As a family of enzymes, the UDP glucuronosyltransferases (UGT) have evolved to eliminate fat-soluble chemicals, we propose that UGTs play a pivotal role in regulating the concentrations of fat-soluble chemicals involved in signaling, and thus are important in controlling gene expression. We intend to provide evidence for this novel role of UGTs in this project. This information will be used to alter the response of the cell to its environment. For example, to help protect the cell against environmental toxins, or to make a cancer cell more susceptible to a chemotherapeutic agent.Read moreRead less
Understanding the mechanisms of class B GPCR-transducer coupling. Current effort in developing drugs targeting G protein-coupled receptors (GPCRs) often result in low success rate due to the lack of understanding of the complexity and the spatiotemporal control of receptor function. The research program aims to understand the molecular mechanisms of receptor/transducer selectivity. The proposal integrated multi-disciplinary approaches to provide a deeper understanding of how the receptor is acti ....Understanding the mechanisms of class B GPCR-transducer coupling. Current effort in developing drugs targeting G protein-coupled receptors (GPCRs) often result in low success rate due to the lack of understanding of the complexity and the spatiotemporal control of receptor function. The research program aims to understand the molecular mechanisms of receptor/transducer selectivity. The proposal integrated multi-disciplinary approaches to provide a deeper understanding of how the receptor is activated responding to different ligands. The anticipated outcome including an enhanced capacity for understanding the fundamental biology, a stronger national and international collaborations. This will provide significant benefits including expanded basic knowledge and improvements in drug development efficiency. Read moreRead less
Determinants of Expression, Assembly and Function of the Noradrenaline Transporter. The noradrenaline transporter protein that is the focus of this project is important for mental health because it belongs to the family of proteins where psychostimulants, such as cocaine, and drugs used in the treatment of depression act. The project will lead to exciting advances in our understanding of how the structure of this protein controls its functions, and potentially to the design of better antidepress ....Determinants of Expression, Assembly and Function of the Noradrenaline Transporter. The noradrenaline transporter protein that is the focus of this project is important for mental health because it belongs to the family of proteins where psychostimulants, such as cocaine, and drugs used in the treatment of depression act. The project will lead to exciting advances in our understanding of how the structure of this protein controls its functions, and potentially to the design of better antidepressant drugs and to the design of drugs to prevent the effects of cocaine.Read moreRead less
Pharmacological modification of retinal and visual function and relation to control of refractive error. Myopia (short-sightedness) affects many hundreds of millions of people worldwide and can lead to blindness. Drug treatments that prevent myopia are being developed, however there is no efficient way of determining who is at risk of myopia or who will benefit from these treatments. This fundamental research project will determine the retinal and visual effects of pharmacologic agents that inhi ....Pharmacological modification of retinal and visual function and relation to control of refractive error. Myopia (short-sightedness) affects many hundreds of millions of people worldwide and can lead to blindness. Drug treatments that prevent myopia are being developed, however there is no efficient way of determining who is at risk of myopia or who will benefit from these treatments. This fundamental research project will determine the retinal and visual effects of pharmacologic agents that inhibit myopia, with the aim of determining an ocular measure that is related to myopia, which is altered by drugs that are known to slow myopia progression, and that could be used as an indication of an agent's likely effectiveness.Read moreRead less