Molecular Epidemiology Of Melioidosis In Australia
Funder
National Health and Medical Research Council
Funding Amount
$357,875.00
Summary
Melioidosis is an important infection in northern Australia. It is a common cause of fatal pneumonia and blood infection in the region. Two outbreaks of melioidosis with fatalities occurring in remote Aboriginal communities have been linked to contamination of the community water supply with the melioidosis bacteria, Burkholderia pseudomallei. In addition, a rare form of melioidosis affecting the brain and spinal cord has resulted in a number of deaths in healthy Aboriginal people and also a num ....Melioidosis is an important infection in northern Australia. It is a common cause of fatal pneumonia and blood infection in the region. Two outbreaks of melioidosis with fatalities occurring in remote Aboriginal communities have been linked to contamination of the community water supply with the melioidosis bacteria, Burkholderia pseudomallei. In addition, a rare form of melioidosis affecting the brain and spinal cord has resulted in a number of deaths in healthy Aboriginal people and also a number left living in remote communities with severe disabilities such as complete paralysis of both legs. Melioidosis has also been identified in two outbreaks occurring over many years in separate locations in southern Australia. It is thought that it may have been introduced to these regions by imported animals, eg via cattle drives, and human fatalities have occurred after local flooding in these temperate locations. This project is built on the ongoing melioidosis collaboration between researchers in Western Australia, the Northern Territory and Queensland. The aim is to use new DNA fingerprinting methods developed specifically for the melioidosis bacteria to understand better why melioidosis can be such a severe disease and how it spreads from the environment to humans and animals and also how it has possibly spread within Australia and overseas. Better recognition and treatment of melioidosis has resulted in a halving of the death rate from this disease in northern Australia (mortality decreased from 40%-18%). This study aims to give us a better understanding of how this soil and water bacteria interacts with humans to cause such severe disease and will hopefully result in new primary preventative measures to complement the improved diagnosis and treatment.Read moreRead less
Hepatic Fibrogenesis In Paediatric Cholestatic Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
Liver disease in children causes a significant impact on lifespan and quality of life. The commonest causes of liver disease in children are cholestatic, or diseases related to obstruction of bile flow out of the liver. In ways we are only beginning to understand, obstruction of bile flow stimulates liver scar formation which, if untreated, leads to replacement of normal liver tissue and ultimately to failure of the liver. In infants, the most common and serious cholestatic liver disease is bili ....Liver disease in children causes a significant impact on lifespan and quality of life. The commonest causes of liver disease in children are cholestatic, or diseases related to obstruction of bile flow out of the liver. In ways we are only beginning to understand, obstruction of bile flow stimulates liver scar formation which, if untreated, leads to replacement of normal liver tissue and ultimately to failure of the liver. In infants, the most common and serious cholestatic liver disease is biliary atresia. It develops at, or shortly after birth with progressive destruction of the bile ducts, responsible for transporting bile out of the liver. Without early diagnosis and surgery these infants develop progressive liver scarring leading to liver failure and death or liver transplantation within 1-2 years. It is the commonest reason for liver transplantation in children (55-60%) in the Western world. Even with successful surgery, most, if not all patients will come to liver transplantation over the subsequent 25 years because of ongoing, but slower, scar formation. In older children, diseases like cystic fibrosis cause bile duct blockages leading to progressive liver scarring that is slower and unpredictable, contributing to ill health in up to 20% of patients and death from end stage liver disease or liver transplantation in 5%. Using liver tissue from children with these two disorders we have been able to identify the key cells that control the liver scar process, the Hepatic Stellate Cell. We now need to investigate the role of bile constituents on the scar-forming process in these two diseases. We will utilise a well characterised animal model to investigate the influence of bile constituents on cells isolated from this model and apply these findings back to patient samples to determine their role in paediatric cholestatic liver disease. This will help us to better understand the disease process and importantly, develop more effective and earlier treatment.Read moreRead less
Role Of Chemoattractants In Hepatic Stellate Cell Recruitment And Fibrogenesis In Paediatric Cholestatic Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$589,175.00
Summary
This project investigates how decreased bile flow in children's liver diseases such as cystic fibrosis and biliary atresia, leads to the release of molecules from the liver which cause recruitment of scar-forming cells. This results in cirrhosis (liver scar) and the necessity for liver transplantation. This project will investigate whether some children are more susceptible to liver scarring due to mutations in genes which cause increased release of these recruitment molecules from the liver.
Role Of HtrA And RseP, Stress Response Proteases, In Development And Persistence Of Chlamydia Trachomatis Infections
Funder
National Health and Medical Research Council
Funding Amount
$389,984.00
Summary
This project will research the most commonly reported bacterial sexually transmitted infection Chlamydia trachomatis. Bacterial proteins which could play a role in chronic infections of humans will be investigated. Proteins will be biologically examined to determine their role during disease. This may identify proteins which could be used for diagnostic and therapeutic tools to prevent chronic Chlamydia infection (which can result in infertility and other serious conditions).
Assessment Of Oxidant Stress And Mitochondrial Dysfunction In Young Adults With Iron Loading Diseases
Funder
National Health and Medical Research Council
Funding Amount
$601,979.00
Summary
Disorders of iron metabolism are particularly prevalent in Australia and the consequences of excess iron can be severe. Liver disease is frequently associated with iron loading. The commonest form of iron loading can be treated readily, but it is unclear when the first signs of tissue damage occur and thus at what stage treatment should commence. This project will examine in detail the relationship between body iron levels and signs of tissue damage in young subjects with iron loading disease.
Which Mental Activities And When For Dementia Prevention? The Four Nations Longitudinal Collaboration
Funder
National Health and Medical Research Council
Funding Amount
$183,218.00
Summary
We will examine the link between lifetime participation in complex mental activities and long term dementia risk in a level of detail not previously possible. Four major studies of brain health from around the world will join forces for the first time to determine which mental activities are most closely linked to protection from dementia, and when during the lifespan these are most important. Mental activity will be assessed using our recently published Lifetime of Experiences Questionnaire.
Recycling Endosomes Governing Cell Polarity And Cytokine Secretion.
Funder
National Health and Medical Research Council
Funding Amount
$958,412.00
Summary
Cytokines are chemical messengers released by cells to mount inflammatory responses to fight infections. The timing and direction of cytokine release must be tightly regulated. We investigate the cellular compartments and molecules that control cytokine secretion using sophisticated live cell imaging. Uncontrolled cytokine release is the main cause of ongoing inflammation in arthritis and inflammatory bowel disease and our studies aim to identify cellular targets for new drug development.
Regulating The Secretion Of Inflammatory Cytokines
Funder
National Health and Medical Research Council
Funding Amount
$558,441.00
Summary
Cytokines or chemical messengers released by cells are essential for controlling immune responses but, in excess, they cause Crohn's disease and arthritis. Our research aims to block cytokine release as a novel way to ameliorate disease. We have identified specific cellular proteins, called golgins, that can be targeted to reduce cytokines. Here, characterization of golgin mediated cytokine transport in cells and in a mouse disease model is necessary to translate these findings for human benefit
Urotensin-II In Human Heart: Investigation Of Mechanisms Involved In Cardiac Function
Funder
National Health and Medical Research Council
Funding Amount
$255,990.00
Summary
The normal function of the body is maintained by naturally occurring compounds. Some for example affect the heart, fine tuning it to make it beat faster or slower, or beat with greater or less force when required in different situations in health and disease. We were the first to show just recently that a small protein which occurs naturally in the body, called urotensin-II can affect the way the heart beats. We showed that extremely tiny amounts increase the force of the heart beat. Our finding ....The normal function of the body is maintained by naturally occurring compounds. Some for example affect the heart, fine tuning it to make it beat faster or slower, or beat with greater or less force when required in different situations in health and disease. We were the first to show just recently that a small protein which occurs naturally in the body, called urotensin-II can affect the way the heart beats. We showed that extremely tiny amounts increase the force of the heart beat. Our findings indicate that urotensin-II is the most potent heart stimulator identified to date. In patients with heart failure, short term stimulation of heart contraction is beneficial, supplying the heart and other organs with vital oxygen and nutrients. However, in the long term excessive stimulation causes worsening of the patients condition. Very little is currently known about the way in which urotensin-II alters heart function. The goal of our study is to understand the mechanism involved in urotensin-II mediated effects on the heart. This will involve identifying the location of urotensin-II and its receptors in the heart, and determining what signalling changes occur after the interaction of urotensin-II with its receptors. Urotensin-II must first be cleaved from a larger drug. We will determine where in the heart this cleavage occurs and whether the process is crucial to the ability of urotensin-II to stimulate contraction of the heart. Since stimulators of heart contraction are detrimental to patients with heart failure in the long term, we will determine whether these patients have more urotensin-II in their blood than patients who do not have heart failure. If the levels of urotensin-II are higher in heart failure patients, it may indicate a need to interfere with the interaction of urotensin-II with its receptors.Read moreRead less