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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
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).
Non-viral Vectors For Targeted Delivery Of RNAi Nucleotides To Cervical Cancers
Funder
National Health and Medical Research Council
Funding Amount
$415,738.00
Summary
RNA interference (or gene silencing) is a new technique whereby we are able to turn off the expression of a particular gene either temporarily or permanently. Cancer is basically a genetic disease where certain protective genes are lost or cancer-causing genes expressed. Gene silencing holds great promise in the treatment of genetic disorders, infectious diseases and cancer. Cervical cancer is caused by infection with the human papillomavirus and the expression of two cancer-causing genes. Using ....RNA interference (or gene silencing) is a new technique whereby we are able to turn off the expression of a particular gene either temporarily or permanently. Cancer is basically a genetic disease where certain protective genes are lost or cancer-causing genes expressed. Gene silencing holds great promise in the treatment of genetic disorders, infectious diseases and cancer. Cervical cancer is caused by infection with the human papillomavirus and the expression of two cancer-causing genes. Using RNA interference we can turn off the expression of these two genes which results in the death of the cancer cell. We are also able to cure mice of tumours derived from human cervical cancer. The major issue with gene silencing is how to deliver it effectively to patients. Here we are investigating novel nanoparticulate systems to deliver this new gene-inhibiting drugs preferentially to the tumour site.Read moreRead less
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.
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
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