Understanding How Toxins Interact With Lipid Membranes And Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$598,220.00
Summary
Chronic pain affects one in five Australians and current treatments have limited effectiveness, with only about one third of patients getting meaningful, pain relief. The aim of the current project is to create alternative treatments for pain that can potentially lead to the reduced suffering and improvement of life quality of many Australians. To achieve this aim we propose to study how spider toxins interact with cells and deactivate sensor targets responsible for chronic pain.
Understanding How Perforin Forms Pores: The Role Of Calcium And Lipids.
Funder
National Health and Medical Research Council
Funding Amount
$797,813.00
Summary
This grant aims to study perforin, a key part of the mammalian immune system. The work will facilitate the development of perforin inhibitors. It is anticipated that these data will be of utility in developing first in class drugs to improve the success of bone marrow transplantation.
Burkholderia Pseudomallei Disulfide-forming Proteins: Structure, Function And Inhibition
Funder
National Health and Medical Research Council
Funding Amount
$707,032.00
Summary
Our research will lead to a better understanding of melioidosis, a disease endemic to Northern Australia and which impacts indigenous communities at twice the rate of the rest of the population. This project will also aim to generate new compounds with the potential for development as treatments against this devastating disease.
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.
Defining The Molecular Mechanisms Of Lyssavirus Replication And Immune Evasion: The P Protein Axis
Funder
National Health and Medical Research Council
Funding Amount
$900,995.00
Summary
Lyssaviruses such as rabies virus (RABV) and Australian bat lyssavirus cause rabies disease, which has the highest case-fatality rate of known infectious diseases, causing >60,000 human deaths/year. Critical to this is a protein produced by the virus that is important for both viral growth and evasion of the host's immune defences. This project aims to understand the molecular mechanisms underlying these processes, which may lead to new approaches to combat currently incurable viral diseases.
Structural Basis Of Substrate Recognition By The Membrane-Associated E3 Ubiquitin Ligases
Funder
National Health and Medical Research Council
Funding Amount
$415,244.00
Summary
Membrane-associated E3 ubiquitin ligases control cellular levels of important immunoregulatory molecules and occur in both host- and virus-encoded forms. Target selectivity maps to the transmembrane domains of ligases and their substrates in a little-studied mode of intramembrane molecular recognition. Our goal is to determine the physical basis of this interaction by establishing which sequences drive the association and providing atomic-resolution structures of the membrane-embedded complexes.
Control Of Immunoreceptor Assembly And Function By Intramembrane Sequence Elements
Funder
National Health and Medical Research Council
Funding Amount
$403,121.00
Summary
The cells of the immune system constantly survey their environment for changes that indicate damage. To sense their surroundings cells employ a host of receptors that are associated with signalling adapter proteins that initiate signalling cascades inside the cell when receptors bind ligands. This project seeks to determine the structural mechanisms of signal propagation across the plasma membrane of immune cells.
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
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