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A significant proportion of Australian children are at health risk due to environmental metal exposure. It is suspected that exposure to metals during the prenatal period can result in permanent impairment. Human studies are, however, limited by lack of biomarkers that accurately measure exposure at specific times of intrauterine development. We are proposing to develop a novel method that utilizes human primary teeth to provide a direct measure of metal exposure during foetal development.
Artificial Synthesis Of The Type III Secretion System Translocon. A New Approach To Vaccine Design
Funder
National Health and Medical Research Council
Funding Amount
$668,742.00
Summary
Today hospitals are plagued with bacterial infections that do not respond to antibiotics. The problem exists because although antibiotics are effective at killing bacteria, this paradoxically also helps the drug-resistant bacteria thrive. We will pioneer a completely new approach to vaccine design that allows us to construct a vaccine that protects us from bacterial infection without killing the bacteria. The vaccine should therefore be far less susceptible to drug resistance.
Characterization And Inhibition Of Higher-order Assembly Signalling In Toll-like Receptor Pathways
Funder
National Health and Medical Research Council
Funding Amount
$711,995.00
Summary
The innate immune system is the first line of defence against pathogens. Inhibitors of innate immune pathways can be developed into therapeutic agents against a number of disorders including chronic inflammatory diseases, such as rheumatoid arthritis. We have discovered a new mechanisms of signaling by a set of key molecules in these pathways, through formation of large assemblies. We will characterize these assemblies and uncover ways to inhibit their formation.
The Molecular Basis For Manganese Uptake By Pathogenic Bacteria.
Funder
National Health and Medical Research Council
Funding Amount
$632,949.00
Summary
Bacterial antimicrobial resistance is an increasing threat to human health. At this point in time, there is an urgent, fundamental need for the development of new antimicrobial strategies. Bacterial infection involves a constant tug-of-war between the pathogen and the human host for the essential nutrients of life, including trace metal nutrients such as Mn. This project seeks to understand the machinery for Mn uptake by pathogenic bacteria as a target for novel antibacterial design.
Molecular And Structural Basis Of Signalling By TIR Domain-containing Adaptors In TLR Pathways
Funder
National Health and Medical Research Council
Funding Amount
$666,417.00
Summary
Humans first detect the presence of pathogens and respond to them through specific pathways termed innate immune pathways. The proposed research will study proteins that participate in these pathways, in particular their three-dimensional structures and how they interact with each other, to understand how they work together to mount an immune response, and to find ways to modulate this response in infectious diseases as well as chronic inflammatory diseases.
Mechanism Of Action Of A Quinazolinone In Models Of PD
Funder
National Health and Medical Research Council
Funding Amount
$667,548.00
Summary
By the time symptoms of Parkinson's disease (PD) appear, 60-70% of the cells in a crucial part of the brain called the substantia nigra have been destroyed and within a few years of diagnosis, most of the remaining cells have died. This project investigates the causes of this cell loss and a how a new class of compounds could interrupts the process. Success in achieving the aims of this proposal will add to our knowledge of the causes of neuronal death in PD
Structural Investigations Of The Bax And Bak Cell Death Apparatus
Funder
National Health and Medical Research Council
Funding Amount
$275,509.00
Summary
Programmed cell death is a process by which the body keeps rogue cells in check. Cancer cells adapt to avoid this process and thus evade this important defence mechanism. This project seeks to understand the machinery that controls programmed cell death at the molecular level. It will provide the atomic details of how this machinery is regulated and how it functions to induce cell death. These insights will provide new avenues for targeting this machinery for a new generation of cancer therapeut ....Programmed cell death is a process by which the body keeps rogue cells in check. Cancer cells adapt to avoid this process and thus evade this important defence mechanism. This project seeks to understand the machinery that controls programmed cell death at the molecular level. It will provide the atomic details of how this machinery is regulated and how it functions to induce cell death. These insights will provide new avenues for targeting this machinery for a new generation of cancer therapeutics.Read moreRead less
Dissecting The Molecular Basis Of Actin Filament Disassembly In The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$576,716.00
Summary
Cell movement by the malaria parasites is fundamental to parasite infection and disease. However, whilst core components of the parasite motor driving movement are known, little is understood about their regulation, in particular actin – the dynamic force behind all parasite motility. Here by dissecting the role of actin-depolymerizing-factor-1, an essential parasite actin regulator, we hope to reveal one of the central processes that underlies motility and develop it into a potential drug targe ....Cell movement by the malaria parasites is fundamental to parasite infection and disease. However, whilst core components of the parasite motor driving movement are known, little is understood about their regulation, in particular actin – the dynamic force behind all parasite motility. Here by dissecting the role of actin-depolymerizing-factor-1, an essential parasite actin regulator, we hope to reveal one of the central processes that underlies motility and develop it into a potential drug target.Read moreRead less
Plasmin is a complex enzyme that performs major roles in removal of blood clots, wound healing and in tumor metastasis. Here we will understand how plasmin function is regulated at the molecular level. These key insights will be of future use in the development of therapeutics targeting the plasmin system in cancer and clotting diseases.
Understanding The Structure And Function Of The Chromosome Condensin Complex
Funder
National Health and Medical Research Council
Funding Amount
$620,731.00
Summary
In order to survive cells need to divide their genetic material (DNA) equally between two daughter cells. For correct cell division to occur DNA has to be correctly packaged into condensed and organised chromosomes. Improper packaging of genetic material can result in unregulated cells that may become cancerous or lead to other genetic diseases such as Down's Syndrome. Understanding the key players regulating this process is vital to allowing researchers to further work in these areas.