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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.
Peptides (mini proteins) have outstanding potential as new drugs for cancer, pain and many other diseases, but their potential has not been realised so far because peptides tend to be unstable in the body. I have discovered a new class of peptides that are ultra-stable and have very favourable pharmaceutical properties. I will use these peptides to develop a new generation of drugs that are more potent and with fewer side effects than traditional drugs.
Structure, Transport And Assembly Of PorB, A Key Invasion Molecule Of Meningococcal Disease
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
When the bacteria that cause meningococcal disease invade cells, they use specialized cell surface pore proteins to hijack the human cell and maintain infection. This research will study the structure of these bacterial pore proteins to help understand how they function to subvert normal cellular processes, and this insight will be important in the development of new treatments for meningococcal disease.
Detailed images of protein molecules underpin our understanding of biological function and our attempts to find new medicines to counter biological malfunction. Proteins belonging to the so-called Bcl-2 family determine whether a cell lives or dies and, because failure to die on cue is a hallmark of many cancers, high resolution images of these molecules will reveal new targets for cancer therapies.
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.