A group of bacteria called Neisseria cause human-specific infections. To initiate infection, the bacteria must produce a hair-like surface structure, the pilus. The pilus consists mainly of a protein called pilin, and we now understand how pilin production is controlled. However 20 other genes are also involved in pilus production. This project aims to understand how these other genes are controlled and coordinated to assemble this structure that is central to the ability to cause disease.
Glycosylation Of Pili In Pathogenic Neisseria: Function In Disease And Potential As A Vaccine Antigen
Funder
National Health and Medical Research Council
Funding Amount
$150,880.00
Summary
Disease caused by Group B Neisseria meningitidis and Neisseria gonorrhoeae remain a significant health problem worldwide. There are currently no vaccines available for either of these bacteria. A surface structure found on these bacteria, called pili, are key in host colonisation and disease. Genetics and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. The role of glycosylation in the disease process is not ....Disease caused by Group B Neisseria meningitidis and Neisseria gonorrhoeae remain a significant health problem worldwide. There are currently no vaccines available for either of these bacteria. A surface structure found on these bacteria, called pili, are key in host colonisation and disease. Genetics and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. The role of glycosylation in the disease process is not known. It is possible that the glycosylation of pili is required for attachment to host cells or perhaps in evasion of the immune system. In our current studies, we have identified and analysed a number of genes involved in pili glycosylation, in bacteria which make structre that are know. We have also identified a series of new genes we believe are also involved in glycosylation. Some of these genes are involved in the biosynthesis of unknown structures and are common in bacteria isolated from patients with meningitis. We will identify these stuctures and characterise bacteria in which these genes have been inactivated so that we can examine the role of pili glycosylation in colonisation and disease. This study has the potential to yield important new information about the process of colonisation and disease, and also has the potential to facilitate novel approaches in vaccine development.Read moreRead less
Mechanisms Of Central Nervous System Disease Induced By Dysregulated Interferon Signalling
Funder
National Health and Medical Research Council
Funding Amount
$618,165.00
Summary
Interferons are proteins that on one hand have been found to protect cells against infectious agents such as viruses but on the other can cause injury and disease in the brain. In this project the way in which interferons affect the brain to bring about these outcomes will be studied. The results of this work will advance our understanding of how interferons function and may lead to better approaches for combating immune and infectious diseases of the nervous system.
Identifying Genes In The HLA Complex That Influence Clinical Course And Susceptibility In Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$725,177.00
Summary
There is no cure for multiple sclerosis (MS), but a person's genetic make-up can influence their susceptibility to developing MS and the symptoms of their condition. Knowing more about these MS genes will help to a) provide better advice concerning a person's risk of developing the disease or their prognosis b) in the design of new treatments. This project aims to identify 'MS genes in a region of the human genome call the HLA complex.
Pelvic organ prolapse in women is associated with poor quality of life. The standard treatment currently available for prolapse is surgery. The evidence for conservative management with physiotherapy is not clear. This randomised controlled trial will examine the effect of physiotherapy treatment, including pelvic floor muscle training, on prolapse symptoms and severity, compared with lifestyle advice only. Appropriate conservative management may reduce the need for surgery and associated costs.
A Computer Alert To Increase Chlamydia Testing Of High Risk Women In General Practice: A Randomised Controlled Trial.
Funder
National Health and Medical Research Council
Funding Amount
$182,575.00
Summary
Chlamydia trachomatis infection is the most common notifiable sexually transmissible infection (STI) in Australia, with over 30,000 infections notified in 2003, rising by 20% each year. Infection with chlamydia can have considerable complications, particularly for women - it is a leading cause of pelvic inflammatory disease and tubal infertility. Unfortunately, as many as 85% of people with infection do not have any symptoms, so are unaware they have chlamydia; yet chlamydia is easy to diagnose ....Chlamydia trachomatis infection is the most common notifiable sexually transmissible infection (STI) in Australia, with over 30,000 infections notified in 2003, rising by 20% each year. Infection with chlamydia can have considerable complications, particularly for women - it is a leading cause of pelvic inflammatory disease and tubal infertility. Unfortunately, as many as 85% of people with infection do not have any symptoms, so are unaware they have chlamydia; yet chlamydia is easy to diagnose with urine tests and easy to treat with single dose antibiotics. Over 65% of infections diagnosed in women are among those aged 16 to 24 years. Internationally, screening programs for chlamydia have reduced the number of people with the infection and have also reduced the rate of complications arising from infection. However, Australia does not have a screening program and only tests about 4% of 16 to 24 year old women, the largest group at risk of infection, each year. We propose to conduct a study which tests the effect of using a computer based alert. This alert is designed to prompt doctors to discuss chlamydia testing with sexually active women aged 16 to 24 years. A group of general practices will be selected. We will randomly allocate some practices to have the alert installed on their computers and the remaining practices will receive no intervention. We will observe both groups of general practices over 12 months and compare their chlamydia testing rates among women aged 16 to 24 years. We estimate that the alert will increase testing rates from the 4% currently tested to 10%. By testing and treating more women with the infection, we can reduce the number of people in the community with the infection. We will also be collecting information about the dollar cost of chlamydia infection to the community. This study will produce valuable information which can be used by government to inform the design of future chlamydia screening and control programs.Read moreRead less
Innate Immunity And Chlamydia Infection: Bacterial:epithelial Cell Cross-talk At The Mucosal Surface.
Funder
National Health and Medical Research Council
Funding Amount
$593,340.00
Summary
Chlamydial infections are the most common sexually transmitted disease in Australia. Infection induces short term immunity that is only partially protective. Furthermore, in many infected individuals the immune response causes inflammation of the fallopian tubes leading to pelvic inflammatory disease, ectopic pregnancy and infertility. In these individuals the initial chlamydial infection may not be cleared and a chronic infection may develop that can be reactivated, perhaps many times, contribu ....Chlamydial infections are the most common sexually transmitted disease in Australia. Infection induces short term immunity that is only partially protective. Furthermore, in many infected individuals the immune response causes inflammation of the fallopian tubes leading to pelvic inflammatory disease, ectopic pregnancy and infertility. In these individuals the initial chlamydial infection may not be cleared and a chronic infection may develop that can be reactivated, perhaps many times, contributing to the ongoing inflammatory response. Evidence from in vitro studies suggests that antibiotics routinely used to treat Chlamydia infection may actually contribute to the development of chronic infection. The stage of menstrual cycle at the time of exposure and oral contraceptive use can also influence susceptibility to infection suggesting that sex hormones influence infection outcomes. The innate or early immune response to infection by reproductive tract epithelial cells, the target cells of chlamydial infection, is believed to initiate the pro-inflammatory immune responses that will develop in some individuals following primary infection, however very little is known regarding this early epithelial cell immune response. In the proposed studies we will use reproductive tract epithelial cell lines, freshly isolated epithelial cells and cervical biopsy explant cultures to define this early innate immune response to chlamydial infection. Using gene-profiling techniques we will identify the types of innate immune response that predispose to long-term inflammatory sequelae. Gene-profiling techniques will also be used to determine why chronic chlamydial infections develop in some individuals and whether antibiotics influence this. Our ultimate aim is to be able to predict which infected individuals are likely to develop long term inflammatory disease and may therefore need more intensive antibiotic therapy or treatments such as therapeutic vaccination.Read moreRead less
Characterisation Of Antigenic Variation Of Neisserial Cell Surface Adhesins, And Their Role In Infection
Funder
National Health and Medical Research Council
Funding Amount
$556,983.00
Summary
A group of bacteria called Neisseria cause human-specific infections. They produce two types of surface proteins termed adhesins, which allow the bacteria to adhere to, and invade, human cells. There is circumstantial evidence to suggest the bacteria can rapidly vary the structure of these adhesins, even within a single infection. This project will determine whether, and how, this variation is occurring, and what effect it has on the ability of the bacteria to cause disease.
Development Of A Vaccine For Genital Chlamydial Infection
Funder
National Health and Medical Research Council
Funding Amount
$207,551.00
Summary
Genital Chlamydia infections are the most common sexually transmitted infection in Australia with annual health costs of 90-160 million dollars. Infection rates in 15-29 olds are increasing at 15-20% per year. Antibiotics are currently the treatment of choice, however antibiotic resistance is increasing and most infections are asymptomatic and not treated in the absence of screening programs. This project aims to develop a genital Chlamydia vaccine using a combination of novel antigens.