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.
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
Determining Modes Of Binding And Activation Of Complex G-protein Coupled Receptor Targets
Funder
National Health and Medical Research Council
Funding Amount
$620,399.00
Summary
The peptide hormones 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 and the related peptide INSL3 with their cell surface receptors and the mechanisms by which the receptors function. The knowledge gained will aid in the design of smaller, more potent and orally active forms of relaxin which will be able to be used as drugs f ....The peptide hormones 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 and the related peptide INSL3 with their cell surface receptors and the mechanisms by which the receptors function. The knowledge gained will aid in the design of smaller, more potent and orally active forms of relaxin which will be able to be used as drugs for the treatment of heart failure.Read moreRead less
Determining Modes Of Binding And Activation Of Peptide G-protein Coupled Receptor Targets
Funder
National Health and Medical Research Council
Funding Amount
$576,538.00
Summary
The neuropeptide relaxin-3 and the peptide hormone INSL5 are recently discovered members of the relaxin peptide family. Relaxin-3 has important roles in stress and feeding whereas INSL5 is a gut hormone. We will study the interaction of relaxin-3 and INSL5 with their cell surface receptors and the mechanisms by which the receptors function. The knowledge gained will aid in the design of smaller, more potent and orally active forms of relaxin-3 and INSL5 for future clinical applications
Specific Roles Of The Transmembrane Exoloops And The LDLa Module In The Activity Of Relaxin And INSL3 Receptors
Funder
National Health and Medical Research Council
Funding Amount
$598,863.00
Summary
The peptide hormone relaxin is currently in clinical trials to treat acute heart failure. The related hormone INSL3 has important roles in fertility. We will continue our previously successful approaches to study the interaction of relaxin and INSL3 with their cell surface receptors and the mechanisms by which the receptors function. The knowledge gained will aid in the design of smaller, more potent and orally active forms of relaxin and INSL3 for future clinical applications.
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.