Affinity-based Profiling Of Bacterial Fe(III)-siderophore Receptors: Design Strategies For Antibiotics And Iron Overload
Funder
National Health and Medical Research Council
Funding Amount
$275,016.00
Summary
In order to establish an infection, bacteria compete with the host for iron, which is in scarce supply. To access iron, bacteria produce compounds called siderophores which bind iron strongly. The iron-siderophore complex, which is unique to each bacterium, is recognised by specific receptors at the bacterial cell-surface and imported for use. In this project, we are using modified siderophores as platforms for bacteria-specific drug design with the aim of producing new antibiotics.
Examination Of The Role Of Biofilms In Infection With Enteropathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$456,382.00
Summary
Many infections are caused by bacteria living in communities, known as biofilms. Enteropathogenic E. coli (EPEC) is a major cause of diarrhoea and results in the death of millions of children annually. We have found a link between biofilm formation by EPEC and disease. In this project we will examine how biofilm formation by EPEC occurs and the contribution of biofilm formation to disease. The results of this study may indicate new ways to treat and prevent E. coli diarrhoea.
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
Regulation Of Bone Resorption And Formation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$5,596,183.00
Summary
Bone is continually being formed and broken down, and these two processes are critical forthe maintenance of a normal skeleton. These processes are dependent upon communication between the bone building and degrading cells, and the hormones growth factors and cytokines that are present in the circulation or produced in bone. The tightly regulated processes of bone formation and degradation need to remain equal, and are essential for the achievement and maintenance of skeletal strength and form. ....Bone is continually being formed and broken down, and these two processes are critical forthe maintenance of a normal skeleton. These processes are dependent upon communication between the bone building and degrading cells, and the hormones growth factors and cytokines that are present in the circulation or produced in bone. The tightly regulated processes of bone formation and degradation need to remain equal, and are essential for the achievement and maintenance of skeletal strength and form. Osteoporosis results from an excess of bone breakdown over formation, and our Program aims to identify the factors that regulate these processes, and develop new therapies that can modify them. We will also determine what it is about bone cell properties that make some cancers, especially those of breast and prostate, particularly prone to spread to bone.Read moreRead less
Genetic Dissection Of Biofilm Development By Non-typeable Haemophilus Influenzae
Funder
National Health and Medical Research Council
Funding Amount
$418,516.00
Summary
The bacterial pathogen non-typeable Haemophilus influenzae (NTHi) is a common cause of chronic infections of the middle ear and of the airways of patients suffering cystic fibrosis, or chronic obstructive pulmonary disease (COPD). These infections are associated with bacterial biofilms that are significantly resistant to both antibiotics and immune defences. This project aims to characterise the process of NTHi biofilm development so that novel diagnostic tools and therapeutics can be developed.
The Role Of Proteoglycans In Contributing To Placental Thrombosis And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$368,269.00
Summary
Fetal growth restriction (FGR) is a pregnancy complication in which the baby doesn�t grow properly in the womb. Growth restricted babies are much more likely to be stillborn. These babies are also at risk of problems later in life such as obesity, diabetes and heart disease. This study investigates molecules in the placenta that may be responsible for causing FGR. If we can understand how these molecules cause the problem of FGR, we may be able to find better ways of treating or preventing it.
Statistical Methods To Assist The Control Of Communicable Diseases, And Their Application
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
A range of programs, such as vaccination schedules and intervention in outbreaks, is in place to reduce our burden of illness from infectious diseases. This project aims to develop new methods, based on models and associated statistical analyses, to help ensure that our control programs are based on the best available evidence. There are five specific themes: 1. Developed methods for predicting major outbreaks of diseases and appy them to Australian data on measles, pertussis and Ross River viru ....A range of programs, such as vaccination schedules and intervention in outbreaks, is in place to reduce our burden of illness from infectious diseases. This project aims to develop new methods, based on models and associated statistical analyses, to help ensure that our control programs are based on the best available evidence. There are five specific themes: 1. Developed methods for predicting major outbreaks of diseases and appy them to Australian data on measles, pertussis and Ross River virus. The new methods will enable timely intervention to reduce the population risk from these diseases, and to guide the proposed elimination of measles from Australia. 2. The current concept of vaccine efficacy, which is central to the epidemiological assessment of vaccines, performs poorly when the vaccine provides only partial protection, when immunity wanes over time and when infected vaccinees have a lower infectivity. A concept of vaccine efficacy will be developed that overcomes these weaknesses. This concept will find widespread use in epidemiology. 3. Data available from 80 outbreak investigations of transmissible diseases will be analysed to assess the relative effectiveness of various intervention steps. 4. A comprehensive model, and associated computer software, will be developed as a tool for assessing the relative merits of different vaccination schedules. It will be applied to address Australian policy issues for vaccination against pertussis, chickenpox and rubella. 5. The method of backprojection for estimating trends in HIV infection and predicting AIDS incidence will be enhanced to incorporate newly available data in which HIV and AIDS diagnoses are linked. This will enable a precise assessment of infection incidence among heterosexuals and other exposure categories with relatively few cases, to ensure that HIV does not spread more widely.Read moreRead less
Representation Of Spatial Coordinate Systems Within Posterior Parietal Cortex And Hippocampus
Funder
National Health and Medical Research Council
Funding Amount
$43,759.00
Summary
To accurately reach for an object or walk from one room to another, our brains need to be able to locate objects around us and detect obstacles in our path. Our amazing ability to make an accurate eye movement directly towards an object such as a cup of tea and move our hand smoothly and directly to the cup is something we all take for granted. However, this ability requires enormous computational complexity which our brains have evolved to handle with ease. We plan to determine the parts of the ....To accurately reach for an object or walk from one room to another, our brains need to be able to locate objects around us and detect obstacles in our path. Our amazing ability to make an accurate eye movement directly towards an object such as a cup of tea and move our hand smoothly and directly to the cup is something we all take for granted. However, this ability requires enormous computational complexity which our brains have evolved to handle with ease. We plan to determine the parts of the brain that perform these computations by using a relatively new technique called functional magnetic resonance imaging or fMRI. This is a non-invasive technique that requires a person to lie in an MRI scanner and perform simple eye movement tasks while the scanner takes images of the brain. With this technology we are able to determine which regions of the brain are most active during the performance of each task, thereby giving us an insight into how the brain works. An area of the brain called the parietal lobe is thought to be involved in the localization of objects, such as reaching for a cup of tea. We will study this area using fMRI to determine how a map of space is represented within the parietal lobe. This region of the brain communicates with another region, the hippocampus which is thought to be involved in navigation, such as walking about the house or driving in the city. Functional MRI will be used to study the hippocampus of our subjects while they perform simple navigational tasks through a maze which is simulated on a computer screen. This will reveal the role hippocampus plays in navigation and the relationship between the parietal lobe and hippocampus. We hope that the greater understanding of hippocampus that will arise from this study will enable us to devise a robust method for imaging hippocampal function with fMRI. We expect that these techniques will aid in the diagnosis of hippocampal abnormalities in patients with temporal lobe epilepsy.Read moreRead less
Characterisation Of Extracellular DNases Of Pseudomonas Aeruginosa And Their Contribution To Disease
Funder
National Health and Medical Research Council
Funding Amount
$418,516.00
Summary
The bacterium Pseudomonas aeruginosa causes a number of serious diseases of humans particularly of immunocompromised patients. We have found that this bacterium secretes enzymes that have the ability to digest DNA. This proposal aims to work out how this bacterium uses these enzymes to infect human tissues and escape killing by immune cells. The results from this study will help to determine if these proteins may be used as targets for the development of new anti-infective drugs.