GENETIC ANALYSIS OF POLYSACCHARIDE CAPSULE BIOSYNTHESIS AND REGULATION IN STREPTOCOCCUS PNEUMONIAE
Funder
National Health and Medical Research Council
Funding Amount
$377,036.00
Summary
Streptococcus pneumoniae (the pneumococcus) is an important cause of invasive diseases such as pneumonia, meningitis and bacteraemia in humans. Many people carry this organism in the nasopharynx asymptomatically. However, in a small proportion, the organism overcomes host defences and invades the body causing life-threatening disease. An essential virulence factor of the pneumococcus is the polysaccharide capsule which protects it from the immune defences of the host during an infection. Until r ....Streptococcus pneumoniae (the pneumococcus) is an important cause of invasive diseases such as pneumonia, meningitis and bacteraemia in humans. Many people carry this organism in the nasopharynx asymptomatically. However, in a small proportion, the organism overcomes host defences and invades the body causing life-threatening disease. An essential virulence factor of the pneumococcus is the polysaccharide capsule which protects it from the immune defences of the host during an infection. Until recently, very little was known of the pneumococcal genes involved in production of this antigen. This project aims to continue characterization of these genes, and examination of the factors which regulate their expression. This regulatory mechanism may be very important, because production of increased levels of the polysaccharide capsule is believed to be an crucial step in the transition from carriage to invasion. An understanding of the molecular events involved in biosynthesis and regulation of capsule production will improve our understanding of the disease process and identify alternative targets for antimicrobial therapy.Read moreRead less
Polysaccharide Biosynthesis As A New Drug Target In Leishmania Parasites
Funder
National Health and Medical Research Council
Funding Amount
$422,517.00
Summary
Leishmania are protozoan parasites that cause a number of important diseases in humans, afflicting more than 12 million people worldwide. There are currently few drugs that target infectious disease causing stages of these parasites. We have recently shown that Leishmania parasites accumulate a highly unusual sugar polymer when they infect mammalian cells, which appears to be important for infectivity. In this proposal , we will investigate how this sugar polymer is made, identify enzymes involv ....Leishmania are protozoan parasites that cause a number of important diseases in humans, afflicting more than 12 million people worldwide. There are currently few drugs that target infectious disease causing stages of these parasites. We have recently shown that Leishmania parasites accumulate a highly unusual sugar polymer when they infect mammalian cells, which appears to be important for infectivity. In this proposal , we will investigate how this sugar polymer is made, identify enzymes involved in its synthesis and develop new chemical tools for generating highly specific inhibitors of Leishmania sugar biosynthesis. This project will provide new insights into processes that are essential for the survival and infectivity of an improtant group of human pathogens, and lead to the development of new classes of enzyme inhibitors with anti-parasite activity.Read moreRead less
Optimising Prevention And Vaccination Policy For Pneumococcal Disease, Influenza And RSV In Indigenous Australians
Funder
National Health and Medical Research Council
Funding Amount
$174,933.00
Summary
Despite recommending pneumococcal vaccine in the Northern Territory since 2000 for Indigenous Australians from 15 years of age, and increasing vaccination coverage, a corresponding reduction in disease has not been observed. This study will provide an evidence base for future vaccination policy by examining whether there is an adequate immune response to pneumococcal vaccination in Indigenous Australians, and whether prior vaccination could reduce the immune response to revaccination.
Analysis Of FGF Receptor Signalling Involved In Lens Cell Proliferation And Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$343,028.00
Summary
Cataract, the loss of transparency of the eye lens, is the leading cause of blindness in the world. An eventual cure for cataract depends on a better understanding of the basic molecular processes in the normal and cataractous lens. Our research has focussed on identifying the molecules that control the formation and maintenance of the lens. Growth factors are important regulators of cell behaviour and our studies have provided compelling evidence that members of the FGF growth factor family pla ....Cataract, the loss of transparency of the eye lens, is the leading cause of blindness in the world. An eventual cure for cataract depends on a better understanding of the basic molecular processes in the normal and cataractous lens. Our research has focussed on identifying the molecules that control the formation and maintenance of the lens. Growth factors are important regulators of cell behaviour and our studies have provided compelling evidence that members of the FGF growth factor family play pivotal roles in lens developmental biology by influencing lens cell proliferation and differentiation. An important finding from our laboratory is that FGF induces lens epithelial cell proliferation and differentiation at different concentrations. The FGFs elicit intracellular responses upon binding to and activating cell surface FGF receptors (FGFRs). The FGFRs are membrane bound tyrosine kinases which upon activation, activate specific signalling pathways leading to a specific cellular response. To understand how FGFs mediate and regulate different responses in lens cells, namely cell proliferation and fibre differentiation, we plan to examine the role of FGFRs in normal lens development using genetically altered FGFRs that will be expressed specifically in lenses of transgenic mice. While it is known that four different FGF receptor genes are expressed by the normal developing lens, it is unknown what role each of these play in the process of lens cell proliferation and differentiation. In addition, as we can reproduce a specific FGF-induced lens cellular response in vitro, we will use our lens explant culture system to dissect the signalling pathway(s) downstream from specific receptor activation and correlate this with a specific cellular response. By identifying the molecules and mechanisms that control the cellular processes essential for normal lens development, we can better understand how disruptions of these processes lead to cataract formation.Read moreRead less
Fatty Acid Biosynthesis In The Malaria Chloroplast As A Drug Target
Funder
National Health and Medical Research Council
Funding Amount
$131,035.00
Summary
Malarial parasites contain a chloroplast similar to that of plants. We recently found genetic evidence suggesting the malaria chloroplast makes fats in the same way as plant chloroplasts. Additionally, we have found that drugs and herbicides that block plant chloroplast fat production stop growth of malaria cultures. Parasitologists had assumed that malaria was unable to make fats and would scavenge them from its human host so we have probably discovered a new metabolic pathway in these parasite ....Malarial parasites contain a chloroplast similar to that of plants. We recently found genetic evidence suggesting the malaria chloroplast makes fats in the same way as plant chloroplasts. Additionally, we have found that drugs and herbicides that block plant chloroplast fat production stop growth of malaria cultures. Parasitologists had assumed that malaria was unable to make fats and would scavenge them from its human host so we have probably discovered a new metabolic pathway in these parasites. We now propose to prove that the drugs work by blocking essential, chloroplast-based fat production in parasites. This could lead to novel treatment of malaria and related parasites.Read moreRead less
Bridging The Gap Between Cartilage Biology And Osteoarthritis Risk Prediction
Funder
National Health and Medical Research Council
Funding Amount
$512,256.00
Summary
Osteoarthritis is a painful and debilitating cartilage disease affecting just under 1 in 10 Australians and costs the Australian economy roughly $12 billion per year. This project will develop computational models of cartilage with the ability to incorporate genetic and environmental risk factors into a predictive model of cartilage disease.
Coenzyme A Synthesis In The Human Malaria Parasite, Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$428,250.00
Summary
Malaria is responsible for hundreds of millions of cases and an estimated 1.5-2.7 million deaths each year. The disease is caused by a microscopic parasite which is becoming increasingly resistant to antimalarial drugs. There is a very real possibility that there will soon be parts of the world in which malaria is an untreatable disease, and there is an urgent need to identify new drug targets. This work focuses on a particular biochemical pathway in the human malaria parasite, Plasmodium falcip ....Malaria is responsible for hundreds of millions of cases and an estimated 1.5-2.7 million deaths each year. The disease is caused by a microscopic parasite which is becoming increasingly resistant to antimalarial drugs. There is a very real possibility that there will soon be parts of the world in which malaria is an untreatable disease, and there is an urgent need to identify new drug targets. This work focuses on a particular biochemical pathway in the human malaria parasite, Plasmodium falciparum. The pathway mediates the conversion of the nutrient, vitamin B5, into a molecule called Coenzyme A. It plays an essential role in the intraerythrocytic parasite and our preliminary data indicate that components of this pathway hold significant potential as antimalarial drug targets. In this project we will use a range of biochemical and molecular biology approaches to characterise in detail the components of this pathway in the parasite and to explore the possibility that compounds that inhibit this pathway may be of value as much-needed new antimalarial agents.Read moreRead less
I have discovered particular factors produced by our white blood cells have the ability to shut down or boost protein production in the gut, pancreas and lung. My vision is to harness these to devise new strategies for treatments for infectious and non-infectious diseases (inflammatory bowel disease, diabetes) that have a high burden on our healthcare system.