Iron, Pseudomonas Aeruginosa And Lung Disease In Cystic Fibrosis.
Funder
National Health and Medical Research Council
Funding Amount
$322,875.00
Summary
Cystic fibrosis (CF) is the most common lethal geneticdisease in Caucasians. The worldwide incidence of the disorder is approximately 1 in 2,500 live births. The most significant clinical manifestation of CF is chronic lung infection, particularly with the bacterium, Pseudomonas aeruginosa. Even with the current aggressive antibiotic treatment regimens most patients ultimately succumb to infection with this organism and die before they reach 40 years-of-age. The overall aim of our work is to inc ....Cystic fibrosis (CF) is the most common lethal geneticdisease in Caucasians. The worldwide incidence of the disorder is approximately 1 in 2,500 live births. The most significant clinical manifestation of CF is chronic lung infection, particularly with the bacterium, Pseudomonas aeruginosa. Even with the current aggressive antibiotic treatment regimens most patients ultimately succumb to infection with this organism and die before they reach 40 years-of-age. The overall aim of our work is to increase the understanding of how P. aeruginosa persists in the CF lung, with the goal of developing more effective therapeutic strategies to eliminate chronic infection with this bacterium. The new perception is that P. aeruginosa bacteria flourish in mucus with a low oxygen content within the CF lung and persist despite aggressive antibiotic therapy because they have adopted an antibiotic-resistant, biofilm mode of growth. This has opened up exciting directions for new therapeutic strategies. Factors in CF mucus that regulate this mode of bacterial growth are potential targets for intervention. Our past work has shown that iron is likely to be one such factor. In this study, we will extend these findings and determine whether using iron-binding chemicals can disrupt these biofims and allow the host immune system and antibiotics to work more efficiently to kill the bacteria. Not only will this study provide further insights into the pathogenesis of P. aeruginosa in CF and the role of iron, but ultimately it will contribute to the improved treatment and prevention of chronic infection with this organism.Read moreRead less
NOD1 Sensing Of H. Pylori Peptidoglycan Promotes Cell Survival And Bacterial Persistence
Funder
National Health and Medical Research Council
Funding Amount
$792,492.00
Summary
The bacterium H. pylori lives in the stomach of half the world’s population and is a major cause of human disease, including peptic ulcers and stomach cancer. This project will investigate how H. pylori is able to manipulate the host immune system by modifying the composition of its outside layer (the cell wall). In so doing, H. pylori causes changes in cells of the stomach lining that allow the bacterium to persist, but that also may predispose the host to cancer.
Understanding The Complex Relationship Between Host, Pathogen And Antibiotic Factors On Treatment Outcome In Serious Bacterial Infections
Funder
National Health and Medical Research Council
Funding Amount
$380,945.00
Summary
Millions of people still die every year from bacterial infections despite the availability of antibiotics. The same bacterial infection in one person can behave very differently in another person, so infections can range from trivial to life-threatening or fatal. Understanding the relationship between the patient, the infecting bacteria and the antibiotic treatment given will ultimately help to predict and improve outcomes for patients with serious bacterial infections.
New Mechanisms Of Immunomodulation By Interferon Transsignaling
Funder
National Health and Medical Research Council
Funding Amount
$540,441.00
Summary
The aim of this project is to characterise a new discovery of how the body can regulate its response to disease such as infections and cancer. Interferons are produced by the body to stimulate immune reactions to these diseases. We have dicovered that a circulating form of an interferon binding protein or receptor can change the nature of an immune response. We plan to study how this is achieved and whether this information can be used therapeutically.
Modulation Of Leishmaniasis By The Proinflammatory Cytokines TNF
Funder
National Health and Medical Research Council
Funding Amount
$288,911.00
Summary
We have established a mouse model that has been genetically modified and cannot produce the cytokine tumour necrosis factor. This cytokine is secreted in the beginning of the inflammatory response. If these mice are infected with a parasite they are not able to heal the infection and die quickly. We can demonstrate that these mice cannot regulate the beginning inflammatory response and do not form a cellular infiltrate at the site of infection.
Bacterial Outer Membrane Vesicles As Immunomodulatory Agents In Helicobacter Pylori Infection
Funder
National Health and Medical Research Council
Funding Amount
$306,510.00
Summary
Chronic inflammation of the stomach is a hallmark of Helicobacter pylori infection, and is a precursor to peptic ulcer disease and cancer. Like many other bacteria, H. pylori sheds spherical blebs from its surface. These blebs bind to stomach cells in vitro and have been found in stomach biopsies of H. pylori-infected subjects. The aims of the work are to investigate the mechanisms whereby H. pylori blebs enter and disseminate within host cells, and how this may contribute to inflammation.
Macrophage Lineage Contribution To Breast Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$602,501.00
Summary
When diagnosed early, breast cancer can be treated with a high degree of success. However, if the cancer spreads to other organs such as lungs and bone, patients suffer from severe pain and debilitating symptoms that often lead to death. Therapies for patients with advanced disease are extremely limited. It is the aim of this project to define the role that macrophages and stromal fibroblasts play in assisting the tumour cells to spread around the body and grow in other tissues.