Novel Small Molecule FosB/AP-1 Inhibitors For The Prevention Of Proliferative Vascular Disorders
Funder
National Health and Medical Research Council
Funding Amount
$343,597.00
Summary
This project examines the effect of a novel FosB/AP-1 inhibitor (LK001) on neointima formation after injury in animal models of restenosis, atherosclerosis and abdominal aortic aneurysm, and a human ex vivo model of graft stenosis Given the current prevalence of CVD in Australia and the increasing demographic of susceptible individuals in the ageing population, this project has enormous clinical implications.
Genetics And Biochemistry Of Biosynthesis Of The Cell Wall Of Mycobacteria
Funder
National Health and Medical Research Council
Funding Amount
$260,831.00
Summary
Mycobacteria commolnly cause human disease. The major killer in the group is Mycobacterium tuberculosis which annually causes millions of deaths from tuberculosis (TB) worldwide. Another pathogen from this group is Mycobacterium avium which often infects immunosuppressed people such as those with advanced HIV-AIDS. Mycobacteria have evolved a specialised wall that surrounds their cells which protects them from chemical attack from antibiotics and helps them to establish infections. The major ant ....Mycobacteria commolnly cause human disease. The major killer in the group is Mycobacterium tuberculosis which annually causes millions of deaths from tuberculosis (TB) worldwide. Another pathogen from this group is Mycobacterium avium which often infects immunosuppressed people such as those with advanced HIV-AIDS. Mycobacteria have evolved a specialised wall that surrounds their cells which protects them from chemical attack from antibiotics and helps them to establish infections. The major antibiotic used for TB stops cells from synthesising the protective layer thereby making them very vulnerable to human immune defences. Unfortunately, resistance to this antibiotic is common and new antibiotics are needed to treat mycobacterial infections. We are studying how mycobacteria make the cell wall and are looking for key steps where new drugs might be able to inhibit the process. Our approach is to inactivate genes in the mycobacteria that make the enzymes which control cell wall synthesis. The gene inactivation results in crippled mycobacteria that are unable to make proper cell walls. We analyse the cell wall changes that gene inactivation cause studying the chemical composition of the cell. This helps to identify the steps in cell wall biosynthesis and each step becomes a potential target for new drugs. Each of the weaken mycobacteria can be tested to see how well they can resist antibiotics and to see if they can survive host defences. In this way we can identify which components of the cell wall are critical for them to establish infections and resist antibiotic treatments. Enzymes that participate in the synthesis of such components are prime targets for us to concentrate on to design new antibiotics.Read moreRead less
Production And In Vivo Delivery Of Bacteriphage Lytic Enzymes By Lactobacillus Fermentum For Disease Prevention.
Funder
National Health and Medical Research Council
Funding Amount
$272,250.00
Summary
Lactic acid bacteria are commonly found in the oral cavity, digestive and female urogenital tracts of humans and other mammals. They are almost completely harmless with only some streptococci and enterococci being able to cause disease. The harmless lactic acid bacteria are mainly classified as Lactobacillus or Lactococcus, and members of of these groups are used in the manufacture of dairy foods such as yoghurt and cheese. Lactobacilli in particular are marketed in a number of health-promoting ....Lactic acid bacteria are commonly found in the oral cavity, digestive and female urogenital tracts of humans and other mammals. They are almost completely harmless with only some streptococci and enterococci being able to cause disease. The harmless lactic acid bacteria are mainly classified as Lactobacillus or Lactococcus, and members of of these groups are used in the manufacture of dairy foods such as yoghurt and cheese. Lactobacilli in particular are marketed in a number of health-promoting or probiotic foodstuffs which are consumed all over the world. We are interested in developing lactobacilli into therapeutic agents which will prevent or treat infections caused by a range of harmful bacteria including the bacteria which cause strep throat and food poisoning. Lactobacilli will be genetically modified to produce enzymes which specifically kill harmful bacteria. These enzymes are from viruses which infect specific bacteria. Using animal models the modified lactobacilli or lactobacilli produced enzymes will be administered orally and tested for their ability to treat possible infections caused by pathogenic bacteria in the oral cavity and intestine. This new therapeutic production and delivery system offers an alternative infectious disease control method to antibiotics. This agent may also be used to control some of the antibiotic-resistant bacteria that are of significant worldwide concern.Read moreRead less
Regulation Of Inflammatory And Epithelial Responses In An Experimental Model Of Chronic Human Asthma
Funder
National Health and Medical Research Council
Funding Amount
$164,061.00
Summary
This project examines how chronic inflammation and scarring develop in the walls of the airways in asthma. The particular role of allergic mechanisms and of specific types of cells that are involved in allergic inflammation will be tested, using a much-improved mouse model of asthma. In this experimental model, which was developed by the investigators, sensitised mice are chronically exposed to low concentrations of aerosolised egg white protein. The proposed studies will involve comparisons wit ....This project examines how chronic inflammation and scarring develop in the walls of the airways in asthma. The particular role of allergic mechanisms and of specific types of cells that are involved in allergic inflammation will be tested, using a much-improved mouse model of asthma. In this experimental model, which was developed by the investigators, sensitised mice are chronically exposed to low concentrations of aerosolised egg white protein. The proposed studies will involve comparisons with animals that are genetically deficient in their ability to produce certain inflammation-related molecules, as well as with mice treated with antibodies to block the action of other such molecules.Read moreRead less
Morphometric Analysis Of Normal Airway Structure In Childhood And The Influence Of A History Of Asthma On This Structure
Funder
National Health and Medical Research Council
Funding Amount
$186,113.00
Summary
The architectural structure of the airways of the lung is thought to have profound effects on airway function. Changes in this structure are believed to be partly responsible for limiting the flow of air into the lung in conditions such as constant wheezing, bronchitis and asthma. Pathological studies carried out on adult lungs have shown that the structure of the airways is indeed altered in patients with lung disease when compared with patients with no history of breathing difficulties. For ex ....The architectural structure of the airways of the lung is thought to have profound effects on airway function. Changes in this structure are believed to be partly responsible for limiting the flow of air into the lung in conditions such as constant wheezing, bronchitis and asthma. Pathological studies carried out on adult lungs have shown that the structure of the airways is indeed altered in patients with lung disease when compared with patients with no history of breathing difficulties. For example, the walls of the airways are much thicker in patients with lung disease. This thickening means that the airways are much narrower and therefore not able to carry as much air as in people with healthy lungs. In addition, the muscle within the airway wall, which is normally very sparse, is much denser in people with asthma and bronchitis. Thus, the airways can be squeezed closed more easily. It is not known if these changes are present in children who have lung disease. X-rays and sophisticated breathing tests suggest that these children may also have thicker walls and more muscle in their airways. The major difficulties in assessing whether such changes are present in children, is the lack of information on the normal structure in infants; how this changes as they grow to adulthood; or if there are any gender differences. This project aims to obtain this information from the airways of male and female children from 0-18 years. This information can then be used as a basis for comparison with the structure found in children with lung disease, in particular asthma, and therefore assist in making assessments as to the cause of their breathing difficulties. With more knowledge about these causes, we will be in a better position to design new and better treatments and produce ways of preventing them ever occurring.Read moreRead less