LRH-1 is a protein that is inappropriately present in cancers of the breast and other tissues. It causes cancer cells to divide and multiply, and therefore it is important to block its activity. There are, however, no treatments available that block LRH-1. This proposal brings together a team of researchers with broad experience. We will use high throughput technologies to identify and characterize novel LRH-1 inhibitors, and demonstrate their efficacy in reducing the growth of cancer cells.
Altered Nuclear Trafficking And Nuclear Body Dynamics As Drivers Of Ataxin-1 Toxicity
Funder
National Health and Medical Research Council
Funding Amount
$755,190.00
Summary
Ataxias are a large group of neurodegenerative disorders in which balance, motor skills and memory are progressively lost. While mutations in specific proteins do cause certain hereditary ataxias, the mechanisms of their detrimental actions is unclear. Our studies probe the toxic mechanisms of the ataxin-1 protein, focusing on its partners and stress-initiated formation of a toxic hydrogel state. The outcomes will define impacts on cellular protein movement in neurodegeneration more broadly.
STABILISING G PROTEIN-COUPLED RECEPTORS FOR DRUG DISCOVERY
Funder
National Health and Medical Research Council
Funding Amount
$628,140.00
Summary
Prescription drugs targeting human proteins called GPCRs are sold as effective treatments for many diseases. However, there are over 800 different types of GPCRs in the human body and only a small fraction is targeted by drugs, mainly because GPCRs are unstable and thus difficult to work with in the laboratory. We are applying newly developed technologies to engineer stabilised ?1-adrenoceptors, a class of GPCRs, for drug discovery against cardiovascular diseases, epilepsy and neurodegeneration
It is estimated that one quarter of people over the age of 65 suffer from some form of memory impairment, mostly in the form of AlzheimerÍs disease. The enormous economic and social costs of the disease and an aging population make it a major health problem. This work will lead to atomic structures of proteins centrally involved in the disease, thus increasing our understanding of the molecular mechanisms of the disease and form the basis for the design of drugs to combat it.
Development Of New Anticancer Drugs Using Sortase-mediated Ligation
Funder
National Health and Medical Research Council
Funding Amount
$618,274.00
Summary
There is a great need for new cancer treatments. We are developing cyclic peptides as the next generation of safe and effective cancer drugs. Cyclic peptides, unlike their linear counterparts, display high stability and oral bioavailability, as well as high solubility and negligible immune response. One of the hurdles is the cyclisation process and we aim to develop enzyme-mediated cyclisation as a convenient and cost effective method for cyclic peptide production.
Enhancing The Immune Response To Disordered Malaria Antigens
Funder
National Health and Medical Research Council
Funding Amount
$643,739.00
Summary
Half of the worlds population live at risk of malaria, and the disease kills half a million people a year, predominantly young children. Despite recent progress, a vaccine with the efficacy required to help control and ultimately eradicate malaria remains out of reach. This project studies an important class of proteins likely to form part of a future malaria vaccine, and will develop new ways to improve their effectiveness as vaccine components.
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.
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.
Rational Development Of Novel Analgesics For The Treatment Of Chronic Pain
Funder
National Health and Medical Research Council
Funding Amount
$595,945.00
Summary
Chronic pain is a major global health problem that currently affects over three million Australians. There are few drugs available for treatment of chronic pain and most have significant side-effects. Individuals lacking a particular type of ion channel known as Nav1.7 are completely insensitive to pain, but are otherwise normal. Block of this channel therefore appears to be an ideal avenue for pain relief. This project aims to produce selective Nav1.7 blockers that can be used as analgesics for ....Chronic pain is a major global health problem that currently affects over three million Australians. There are few drugs available for treatment of chronic pain and most have significant side-effects. Individuals lacking a particular type of ion channel known as Nav1.7 are completely insensitive to pain, but are otherwise normal. Block of this channel therefore appears to be an ideal avenue for pain relief. This project aims to produce selective Nav1.7 blockers that can be used as analgesics for treating chronic pain.Read moreRead less
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