PrtFII, A Streptococcus Pyogenes Fibronectin Binding Protein, And Invasive Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$296,540.00
Summary
Our recent work revealed that, in the Aboriginal population, young age is a risk factor for severe invasive diseases caused by group A streptococcus. For group A streptococcus infection to occur, bacterial attachment is the first step. The bacterium attaches to host cells through interactions involving host fibronectin and the pathogen's fibronectin-binding proteins. We have found that streptococcal strains from severe disease cases are more likely to have the gene for PrtFII, a fibronectin bind ....Our recent work revealed that, in the Aboriginal population, young age is a risk factor for severe invasive diseases caused by group A streptococcus. For group A streptococcus infection to occur, bacterial attachment is the first step. The bacterium attaches to host cells through interactions involving host fibronectin and the pathogen's fibronectin-binding proteins. We have found that streptococcal strains from severe disease cases are more likely to have the gene for PrtFII, a fibronectin binding protein, than those from uncomplicated skin sores. In this application we propose to extend this observation and compare biochemical properties of PrtFII from strains belonging to the above two sets of collections. We hypothesise that PrtFII from invasive strains bind to fibronectin more tightly than the proteins from strains that cause uncomplicated infection. We also will test whether sera from invasive disease cases have lower titre of antibodies to the conserved region of PrtFII than sera from uncomplicated cases. A streptococcal vaccine by necessity has to be a multi-component vaccine to cover a wide spectrum of diseases and epidemiological differences. The study proposed here may provide a basis to argue whether or not to include PrtFII in such a multi-component vaccine.Read moreRead less
Infectious pathogens invade cells by hijacking cellular pathways, termed endocytosis, that normally internalise material from outside the cell. We will identify the molecular details of these pathways and how they are modulated in response to infection with Salmonella, a leading cause of human gastroenteritis. Such studies are necessary in order to understand host-pathogen interactions so that treatments can be developed targeting the symptoms of infection
Uropathogenic Escherichia coli (UPEC) are a major cause of urinary tract infections (UTI) and sepsis. Recently, a highly virulent clone of UPEC (E. coli ST131) that is resistant to multiple types of antibiotics has emerged worldwide. This project addresses the mechanisms by which E. coli ST131 can colonise the urinary tract and cause disease. The outcomes of this project will be a better understanding of how E. coli ST131 causes disease, and potentially new treatment regimes for UTI.
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.
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
Mechanism Of Action Of Sec1p-like Proteins In Membrane Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$234,936.00
Summary
One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has ....One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has developed a complex assembly line of modifications that are added to proteins in a specific order as they travel to their final destination within the cell. This necessitates the accurate passage of molecules between compartments, a process known as vesicle transport. To orchestrate the complex network of vesicular transport steps between all of the various intracellular compartments it is necessary to employ complex machinery to guide and check that these steps occur with high fidelity. The goal of our research proposal is to define the function of one of the molecules involved in this control process, the so-called Sec1p proteins. The strength of our proposal lies in the diversity of our approach. We intend to explore the molecular advantages of a relatively simple eukaryotic organism, a yeast cell, and apply the findings obtained from this cell to a more complex but highly related vesicular transport process; that of the insulin-regulated movement of a glucose transporter in mammalian fat and muscle cells. While we intend to apply our findings to the treatment of patients with diabetes, it is our ultimate goal to be able to learn more about this fundamental cell biological process so that we can apply our knowledge to understanding many different disease states.Read moreRead less
Enhancing Erythropoietin Therapy In Ischaemia-reperfusion Injury Of Heart And Kidney
Funder
National Health and Medical Research Council
Funding Amount
$361,021.00
Summary
Heart attacks and kidney disease from a lack of blood flow are common causes of morbidity and have poor treatment options. Erythropoietin (epo) is a useful new treatment, but there remain some caveats to its use in humans: eg. it may cause excessive scarring during repair. Use of epo with an anti-inflammatory drug may decrease scarring and provide benefit to long-term health. We plan to carefully define the biomolecular pathways of injury and repair, to better plan this therapy for human use.
Reliability Of An Online Geriatric Assessment Procedure
Funder
National Health and Medical Research Council
Funding Amount
$343,822.00
Summary
This study will examine the reliability, safety and cost of a novel new method of providing geriatrician assessment to older people in hospital. Nurses consult with the patient and enter their findings on a web-based software system that enables the geriatrician to review, report and make recommendations over the internet.
Impact Of DTP Schedules On The Immunogenicity Of 2 Doses Of 13v-PCV Followed By An Early Booster
Funder
National Health and Medical Research Council
Funding Amount
$2,651,687.00
Summary
This project aims to come up with a vaccination schedule to make pneumococcal vaccines more effective and affordable for Fiji and other developing countries. We will evaluate schedules involving a 2 dose primary series in early infancy with a booster at 9 months of age. We will compare the immune responses to 3 different primary series and 2 booster options. The results of this project will be used to provide advice, at global and country levels, regarding introduction of pneumococcal vaccines.
Using Conversational Computer Technology To Improve Diabetes Management: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$708,606.00
Summary
The diabetes epidemic is a growing challenge for the Australian health care system with over 1 million Australians living with diabetes. The impact on individuals' lives and the whole of Australian society is very substantial indeed. There is very good evidence that this impact would be reduced by developing new approaches to manage the disease and facilitate improved self-management. Recent developments in information and communications technologies offer some promising new ways and tools for a ....The diabetes epidemic is a growing challenge for the Australian health care system with over 1 million Australians living with diabetes. The impact on individuals' lives and the whole of Australian society is very substantial indeed. There is very good evidence that this impact would be reduced by developing new approaches to manage the disease and facilitate improved self-management. Recent developments in information and communications technologies offer some promising new ways and tools for achieving this. This research will evaluate a computer-controlled, interactive telephone system for improving the management and self-management of Type 2 diabetes in addition to routine care. Patients with Type 2 diabetes will be recruited from Brisbane and each patient will be randomly assigned to receive either this new program or just their usual care from their doctor or Diabetes Clinic. The first group will call the system weekly for six months using a regular phone or a mobile phone if they wish. During the call, they will answer questions by speaking into the phone, listen to feedback and strategies for improving management of their diabetes and then discuss their next targets and behavioural actions. They will receive systematic and tailored advice on blood glucose testing, nutrition and physical activity, as well as medication taking and foot care. The system individualises conversations according to the user s answers and responses over all the interactive sessions. The trial will formally evaluate the clinical impact on blood glucose control and the adoption and maintenance of the targeted health habits, as well as the intervention s cost-effectiveness and users satisfaction with the system. This project s significance lies in the excellent potential of using this new technology to provide a 'low cost' but effective program to help people better manage Type 2 diabetes.Read moreRead less