Structural Investigations Of Bacterial Evasion Of IgA Mucosal And Systemic Immunity
Funder
National Health and Medical Research Council
Funding Amount
$488,812.00
Summary
Nose, throat and skin infections are often caused by streptococcal and staphylococcal bacteria, known as Strep Throat and Golden Staph. Infections can be life-threatening in newborns, the elderly or individuals with weak immune systems. These bacteria make proteins bind and inactivate immune proteins. Our research examines the structural basis for bacterial interactions with a key immune system protein (an antibody called IgA) and may lead to new prevention and treatment strategies.
Crohn's disease is a severe, chronic inflammatory disease of the gut which affects up to 50,000 Australians. The majority of patients develop the disease in their twenties, with significant impact on their quality of life. Our preliminary work has identified a novel gene, which could potentially cause a critical reduction in the production of anti-bacterial proteins by cells in the small bowel. Exploring the function of this gene in relation to clinical outcome could lead to better treatment.
Some of the world's most important diseases, including important diseases of indigenous chilren and the hospitalised elderly are caused by bacteria that carry a surface coating called a capsule. It is not clear how this capsule is retained by bacteria. Resolution of this question could lead to the development of new disinfectants that will stop hospital-acquired infections, to new reagents that can be incoporated into medical devices where bacteria frequently grow, and new antibiotics.
Evolution And Function Of A Novel Lateral Flagellar Locus, Flag-2, In Pathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$465,158.00
Summary
This project will study how the bacteria that cause infant diarrhoea colonize the intestine and induce disease. We have identified a novel genetic region that allows E. coli to survive and persist in the intestine. Similar genes are also present in closely related organisms. This project will help us to undestand how new diseases evolve and emerge and may lead to the development of new vaccines to protect against infant diarrhoea.
Contribution Of Nuclear Targeting Of The NleE-OspZ Family Of Proteins To Escherichia Coli And Shigella Virulence
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
This project will study how the bacteria that cause infant diarrhoea colonize the intestine and induce disease. We have identified new bacterial proteins that allow E. coli to manipulate the normal host cell processes involved in killing an invading bacterium. Similar proteins are also present in the closely related organism, Shigella which causes dysentary. We will determine how these proteins act by finding the host cell proteins they bind.
Characterisation Of A Novel Type Of Promoter Controlling Expression Of Virulence Genes In Neisseria.
Funder
National Health and Medical Research Council
Funding Amount
$200,880.00
Summary
This project will investigate how two different types of bacteria control genes that are involved in determining their disease-causing ability. The expression of many bacterial genes is controlled by a sophisticated battery of regulatory systems that respond to individual, very specific, environmental signals. Such regulatory systems are capable of exerting very precise control over the level of gene expression, in response to the concentration of specific molecules in the immediate environment. ....This project will investigate how two different types of bacteria control genes that are involved in determining their disease-causing ability. The expression of many bacterial genes is controlled by a sophisticated battery of regulatory systems that respond to individual, very specific, environmental signals. Such regulatory systems are capable of exerting very precise control over the level of gene expression, in response to the concentration of specific molecules in the immediate environment. However, there is evidence to suggest that many important disease-causing bacteria are much less reliant on specific regulatory systems. Instead, these bacteria rely more heavily what have been termed global systems for the regulation of gene expression. Such systems typically respond to less specific signals, such as the growth rate of the bacterial cell, but nevertheless appear capable of very precise control. We have evidence for a previously uncharacterised type of global control system that appears to be widespread amongst bacteria. It is likely that many virulence genes in a variety of disease-causing bacteria will prove to be controlled by similar means. Therefore this project will not only provide an insight into how expression of these particular virulence determinants is regulated, but will yield data that may help in our understanding of precise global regulatory processes in other bacterial species of medical importance.Read moreRead less
Cell Surface Mucins In Gastrointestinal Mucosal Innate Immunity
Funder
National Health and Medical Research Council
Funding Amount
$475,500.00
Summary
Epithelial cell surface mucins are large complex proteins found on the surface of all mucosal epithelial tissues, for example in the respiratory, gastrointestinal, reproductive and urinary tracts. We have recently identified three of the seven genes currently known to produce this type of molecule. We propose that mucins have a very important role in maintaining the barrier between potentially infectious microorganisms often present in epithelial tracts and the internal organs. We also believe t ....Epithelial cell surface mucins are large complex proteins found on the surface of all mucosal epithelial tissues, for example in the respiratory, gastrointestinal, reproductive and urinary tracts. We have recently identified three of the seven genes currently known to produce this type of molecule. We propose that mucins have a very important role in maintaining the barrier between potentially infectious microorganisms often present in epithelial tracts and the internal organs. We also believe that these molecules trigger epithelial cell defensive responses to the presence of microorganisms. The proposed research aims to prove these propositions and to elucidate the molecular mechanisms underlying function of cell surface mucins. Understanding the function of cell surface mucins could lead to the development of new drugs to treat epithelial inflammation such as that seen in inflammatory bowel diseases and respiratory diseases such as asthma and cystic fibrosis.Read moreRead less
Origins And Relationships Of Shigella And Enteroinvasive Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$377,310.00
Summary
Shigella is a well known highly infectious human pathogen with as few as 10 cells allowing effective spread by infected food or water, and also by person to person contact. Shigellosis is a particularly significant disease for children due to lack of pre-existing immunity and greater chance of transfer by fecal-oral route. One group of E. coli called Enteroinvasive E. coli (EIEC) resembles Shigella in many aspects from disease symptoms to biochemical properties. EIEC is a major cause of diarrhoe ....Shigella is a well known highly infectious human pathogen with as few as 10 cells allowing effective spread by infected food or water, and also by person to person contact. Shigellosis is a particularly significant disease for children due to lack of pre-existing immunity and greater chance of transfer by fecal-oral route. One group of E. coli called Enteroinvasive E. coli (EIEC) resembles Shigella in many aspects from disease symptoms to biochemical properties. EIEC is a major cause of diarrhoea in less developed countries and has also caused large outbreaks in developed countries. It is now clear that Shigella and E. coli are really one species. EIEC and Shigella strains are variants of E. coli with humans as the only host. However separation of the two in all records and most studies means that there is no integrated understanding of the forms. We aim to study the relationships of Shigella and EIEC and expect significant insights into the origins of Shigella-EIEC. This will facilitate diagnosis and understanding of the disease(s) and lead to a far better classification . EIEC-Shigella strains have arisen from other E. coli independently. This has happened seven times in the derivation of Shigella and we expect more such events with EIEC. An interesting phenomenon during this process is that strains tend to lose metabolic functions. In this study we will look at what, why and how functions are lost. O antigens are important in evading the host immune system. Shigella strains obtained many O antigens, the majority apparently from other species. This is quite likely the key to its success. We will look at how Shigella obtained new O antigens. This project will be significant in the understanding of Shigell-EIEC, a very significant human pathogen, and in general for understanding emergence of new pathogens.Read moreRead less
Investigation Of The Role Of Specific Mucous Associated Bacteria In Children And Young Adults With Crohns Disease
Funder
National Health and Medical Research Council
Funding Amount
$431,764.00
Summary
The role of bacteria in Crohn's disease is well accepted however to date no conclusive agents have been identified. Recent animal studies have implicated mucus-associated bacteria. We have recently shown that such bacteria, the Helicobacteriaceae, are present in humans and children with Crohn's disease. The aim of this project is to determine in children and young adults the role of these bacteria in IBD thus providing information that could be used to design improved therapies for IBD.
Cell Surface Mucins In Gastrointestinal Infection And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$591,967.00
Summary
Mucosal tissues, such as the gastrointestinal and respiratory tracts, are the most common site of infectious disease. We have found that the cells in these tissues produce molecules on their surface, known as mucins, that protect from infection. In the case of chronic infection the mucins prevent the inflammation that underlies the development of cancer. In this project we will be exploring the mechanisms by which mucins prevent infection and inflammation.