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Molecular Characterisation Of Receptor Activity Modifying Proteins (RAMPs)
Funder
National Health and Medical Research Council
Funding Amount
$340,399.00
Summary
The maintenance of optimum health and function of living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific receiver protein at the cell surface called a receptor. In one class of such receptors called G protein-coupled r ....The maintenance of optimum health and function of living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific receiver protein at the cell surface called a receptor. In one class of such receptors called G protein-coupled receptors, the transmission of the message to the interior of the cell involves yet another protein called G protein. These receptors are the most abundant type of cell surface receptors and form the targets for nearly 50% of currently used therapeutic drugs. It is, therefore, extremely important to unravel how each of these components works. To make this process even more complex, it was recently shown that another newly discovered group of proteins called receptor activity modifying proteins (RAMPs) too play a critical role in some systems. We have shown that RAMPs interact with many G protein-coupled receptors and that they have a wider range of actions than has previously been appreciated. Moreover, it has been shown that the RAMP-receptor interface is a viable target for drug development. Understanding the extent to which RAMPs interact with G protein-coupled receptors, how they interact with the receptors and the consequences of this interaction forms the basis of the current proposal. Such knowledge is central to the unraveling of the processes involved in the maintenance of health, abnormalities that lead to disease, and in the development of new treatments.Read moreRead less
Understanding Selective Drug Signaling At G Protein-coupled Receptors
Funder
National Health and Medical Research Council
Funding Amount
$362,206.00
Summary
The maintenance of optimum health and function living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific reciever protein at the cell surface called receptor. In one class of such receptors called G protein-coupled recept ....The maintenance of optimum health and function living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific reciever protein at the cell surface called receptor. In one class of such receptors called G protein-coupled receptors, the transmission of the message to the interior of the cell involves yet another protein called G protein. These receptors are the most abundant type of cell surface receptors and form the targets for nearly 50% of currently used therapeutic drugs. It is, therefore, extremely important to unravel how each of these components works, and in particular to know how they work in living cells. This project utilizes state-of-the-art methodologies to examine interactions between receptors and their cognate G proteins, in living cells and in real-time. The work will answer fundamental questions about the nature of G protein-coupled receptor signaling, in particular whether new classes of drugs can be identified that more selectively activate signaling pathways or factors that attenuate signaling. This work has potential for future development of more effective therapeutic agents.Read moreRead less
A major obstacle to the development of safer and more effective pain treatments is the poorly defined nature of the different pathways involved in chronic pain. The applicant team bring together a unique set of research expertise in using neurotoxins to define, at the molecular level, how the nervous system functions. The applicants also share a common interest in understanding and improving treatments for pain, especially chronic pain which continues to remain poorly managed Through a focus on ....A major obstacle to the development of safer and more effective pain treatments is the poorly defined nature of the different pathways involved in chronic pain. The applicant team bring together a unique set of research expertise in using neurotoxins to define, at the molecular level, how the nervous system functions. The applicants also share a common interest in understanding and improving treatments for pain, especially chronic pain which continues to remain poorly managed Through a focus on pain research, the Program will significantly enhance the scope of existing multidisciplinary collaborations between the Cis Lewis Alewood, Adams and Christie, which have already made a considerable impact in the fields of pharmacology and neuroscience. The CIs also have considerable experience in the development of pain therapeutics, having discovered two conopeptides now under commercial development with AMRAD (AM336) and Xenome Ltd (Xen2174). This Program will discover and use highly selective conopeptides such as these to dissect the pharmacology of peripheral pain pathways and their projections into the central nervous system, and to identify and characterise new targets amenable to drug intervention. The long-term goal of the Program is to discover new targets in pain pathways and develop conopeptides that act on these targets in animal models of chronic pain. These molecules will be optimised within the Program to the point where they can be considered for pre-clinical development in collaboration with commercial partners.Read moreRead less