How Does Fra-1 Regulate The Invasive Properties Of Tumour Cells?
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Most cancer deaths occur when tumours spread and destroy vital body functions. The invasion of tumour cells into surrounding tissue is a critical step during the spread of cancer. This project aims to unravel the molecular mechanisms that control the ability of tumour cells to invade into surrounding tissue and subsequently spread to other sites in the body. We expect to identify potential targets to better diagnose and treat the spread of cancer.
Regulation Of Actin Polymerization During Malaria Parasite Invasion Of The Human Erythrocyte
Funder
National Health and Medical Research Council
Funding Amount
$318,147.00
Summary
Malaria parasites depend on successful invasion of red blood cells for their survival. Invasion is powered by a molecular motor based on two key proteins: actin and myosin. Non-specific drugs that inhibit parasite actin block invasion, demonstrating how important its regulation is to parasite success. This project will study several newly identified malaria actin-regulators, aiming to identify new drug targets that will block malaria actin function, stop motility and as such prevent disease.
Investigating Cytoskeletal Dynamics Across The Lifecycle Of The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$387,741.00
Summary
During its lifecycle the malaria parasite must cross tissues and invade cells in two very different hosts - humans and mosquitos. Although the molecules that drive this process are known, we know nothing about their dynamics in live parasites. Here, we will use state-of-the art microscopy and genetics to dissect parasite motility, tracking proteins in the parasite cell on their journey from human host through to the mosquito - utilising the first Australian malaria-dedicated insectary.
A Study Of The Molecular Epidemiology And Virulence Determinants Of Enterovirus 71 Strains From The Asia-Pacific Region
Funder
National Health and Medical Research Council
Funding Amount
$286,325.00
Summary
In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to ....In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to poliomyelitis. There has been a large increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997, including a large epidemic in Perth, Western Australia in 1999. These epidemics have resulted in many deaths and cases of severe neurological disability. In view of the severity of EV71 neurological disease and the lack of effective treatments, our research effort needs to focus on prevention through public health surveillance and vaccine development. The major aims of our study are two-fold: 1. To study the origin and evolution of EV71 in the Asia-Pacific region using molecular techniques and to use this information to implement surveillance in Australia and Southeast Asia. It is anticipated that improved surveillance will provide early warning of impending epidemics. 2. To understand the molecular basis of virulence of EV71, with emphasis on the ability of virus to cause severe disease of the central nervous system. This study will have two goals: a. To identify the human cellular receptor of EV71. The ultimate goal of this research will be the development of a small animal model of EV71 encephalitis by constructing a transgenic mouse expressing the human cellular receptor for EV71. b. To construct an infectious cDNA clone of EV71 and to develop genetically defined attenuated strains by mutagenesis of the infectious clone. Mutant strains of EV71 will be tested for replication and virulence in newborn mice and in human neuroblastoma cells.Read moreRead less
Identification Of The Plasmodium Falciparum Translocon That Exports Parasite Proteins Into Their Erythocytic Hosts.
Funder
National Health and Medical Research Council
Funding Amount
$409,027.00
Summary
Up to 10% of the world's population will suffer from malaria in any given year and for over a million this disease will be fatal. This devastating disease is caused by the parasite Plasmodium falciparum that infects and destroys our red blood cells. Infected red cells are greatly modified by the parasites so they can feed and avoid elimination by the human immune system. We wish to investigate the red blood cell modification process and assess it as a potential target for anti-malarial drugs.
Dissecting The Pseudoexfoliation Syndrome With Complementary Genetic, Proteomic And Biophysical Strategies
Funder
National Health and Medical Research Council
Funding Amount
$490,352.00
Summary
Pseudoexfoliation syndrome (PEX) is an eye condition in which flaky material deposits in the eye, greatly increasing the risk of cataract and glaucoma which can lead to blindness. PEX is also associated with heart disease, strokes and aneurysms. Cataract surgery in PEX patients has a higher rate of complications. In this project we will determine the nature of PEX material and why it forms. This knowlege will facilitate better diagnosis and treatment of PEX preventing associated blindness.
Can Skin Infection With Group A Streptococcus Cause Acute Rheumatic Fever?
Funder
National Health and Medical Research Council
Funding Amount
$459,450.00
Summary
It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of ....It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of the cause of ARF, and have important implications for prevention of ARF around the world. Presently, these approaches focus on diagnosing and treating sore throat, but no country has proven that such a program can be successful in substantially reducing new cases of ARF. If it was known that skin infection could lead to ARF, then countries (including Australia) could emphasise the importance of skin health programs. A further benefit of this knowledge would be to influence GAS vaccine development, which presently is largely focused on the prevention of sore throat. A different possibility has recently been raised - that the cause of ARF may not always be GAS, but instead that the related bacteria GCS and GGS may have the potential to cause this disease. Proof of this hypothesis would even more dramatically alter our understanding of disease causation, prevention, and vaccine development. We propose to determine the cause of ARF in Aboriginal communities by regularly swabbing families of people with a history of ARF, and using genetic fingerprinting of the bacteria from the skin and throat swabs. When cases of ARF occur, we will be able to determine the site and type of infection that precipitated the attack. We will conduct a related study in more communities, in which we will swab family members of people with ARF and of control families (without ARF) to determine the bacteria most commonly isolated from ARF families.Read moreRead less
MicroRNA Networks That Safeguard The Functional Program Of Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$457,941.00
Summary
A newly discovered group of molecules termed microRNAs are thought to function as rheostats for the activity of genes. We have shown that these molecules are critical for the function of an immune cell type termed regulatory T cells. Without these cells, the immune system is unable to prevent uncontrolled and destructive inflammation. This proposal aims to utilize diverse technologies to uncover the precise molecular mechanisms by which microRNAs safeguard the function of regulatory T cells.
Dissemination And Virulence Properties Of The She Pathogenicity Island Of Shigella Flexneri.
Funder
National Health and Medical Research Council
Funding Amount
$110,625.00
Summary
Bacterial species belonging to the genus Shigella are responsible for intestinal diseases ranging from mild diarrhoea to life threatening bacillary dysentery. Such diseases kill over a million people, mainly infants in developing countries, every year and lead to serious morbidity and mortality even in industrialised countries with well developed health care systems. In many cases the virulence of Shigella species is augmented by large fragments of DNA, called pathogenicity islands, that carry g ....Bacterial species belonging to the genus Shigella are responsible for intestinal diseases ranging from mild diarrhoea to life threatening bacillary dysentery. Such diseases kill over a million people, mainly infants in developing countries, every year and lead to serious morbidity and mortality even in industrialised countries with well developed health care systems. In many cases the virulence of Shigella species is augmented by large fragments of DNA, called pathogenicity islands, that carry genes which contribute to the development of disease (pathogenesis) in humans. Pathogenicity islands are important genetic elements which appear to spread independantly throughout bacterial populations and therefore contribute to the emergence of new virulence traits in bacteria. Recently, we identified two related pathogenicity islands carried by both Shigella flexneri and other species of the genus Shigella. The two pathogenicity islands belong to a unique class of genetic elements found in Shigella species and virulent strains of the intestinal bacterium E. coli. Our current study is aimed at (1) understanding the mechanisms by which one of these islands, the she pathogenicity island, spreads from one bacterial strain to another to introduce disease-producing or virulence genes to new bacteria and (2) to study how the sigA virulence gene, carried on the she pathogenicity island, contributes to disease development in humans. We know that sigA encodes a protein toxin which contributes to the loss of fluid from the intestines of rabbits that have been experimentally infected with Shigella flexneri. We propose to study the structure and function of the SigA protein to determine how it interacts with tissues to produce a pathological state. Such studies will enhance our understanding of the process of disease development and contribute to the investigation and assessment of new strategies for therapeutic intervention.Read moreRead less
Finding The Genetic Causes Of Asthma: The Australian Asthma Genetics Consortium (AAGC)
Funder
National Health and Medical Research Council
Funding Amount
$1,697,639.00
Summary
Asthma is a major burden on individuals and health systems. Despite many decades of research, no major effective new treatments for asthma have emerged recently. We will establish a large international consortium to systematically test nearly all known human genes to identify those that influence asthma susceptibility. We expect to identify pathways not previously implicated in asthma and so lead to a potential breakthrough in the development of more effective treatments.