Host Parasite Interactions: Disease, Pathogenesis And Control
Funder
National Health and Medical Research Council
Funding Amount
$13,738,897.00
Summary
Our program will investigate two major global parasitic diseases: malaria and leishmaniasis. We will explore how the parasites identify and invade the host. This is a critical stage of the infection and we will characterise proteins involved as they are potential targets for drugs and vaccines against the parasites. Many of these recognition and interaction components are excellent candidates for the development of vaccines to interrupt the cycle of infection. We are also unravelling metabolic p ....Our program will investigate two major global parasitic diseases: malaria and leishmaniasis. We will explore how the parasites identify and invade the host. This is a critical stage of the infection and we will characterise proteins involved as they are potential targets for drugs and vaccines against the parasites. Many of these recognition and interaction components are excellent candidates for the development of vaccines to interrupt the cycle of infection. We are also unravelling metabolic pathways unique to the parasites using a mixture of genetic and computational tools complemented with sophisticated instrumentation to chemically identify the parasite�s entire repertoire of metabolic compounds. These pathways, absent from human hosts, are also highly vulnerable and we will feed the key steps into the drug development facet of the program. Our program also looks at how the parasites cause disease and how the host responds to the disease. We will explore the reactions of the immune system to infection and consequences of the body�s (often only partially successful) attempts to fight off the disease.Read moreRead less
Analysing the protective role of platelets during malaria infection. Platelets protect the host during malarial infection. This project aims to study how platelets kill the malaria parasite by investigating the role of host molecules and their potential as novel antimalarial agents. The role of platelets in the pathogenesis of cerebral malaria syndrome will also be investigated.
Cholera Toxin Co-receptor Interaction In The Prevention Of Inflammatory Autoimmune Disorders
Funder
National Health and Medical Research Council
Funding Amount
$359,577.00
Summary
Vaccination is undoubtedly one of mankind's greatest achievements. While infections continue to be the major cause of morbidity and mortality in the developing world, heart disease, cancer, chronic allergies and autoimmune disorders are taking their toll in advanced societies. Our expanding knowledge of these 'modern diseases' shows that the immune system plays a central role and hence it is important to learn if new immunologically-based therapies can be developed for such chronic human disorde ....Vaccination is undoubtedly one of mankind's greatest achievements. While infections continue to be the major cause of morbidity and mortality in the developing world, heart disease, cancer, chronic allergies and autoimmune disorders are taking their toll in advanced societies. Our expanding knowledge of these 'modern diseases' shows that the immune system plays a central role and hence it is important to learn if new immunologically-based therapies can be developed for such chronic human disorders. This project takes advantage of our recent discoveries on the immunological properties of a hitherto feared molecule - cholera toxin. We have shown that one portion of the toxin, the B-subunit, responsible for binding to cell membranes, possesses remarkable immunomodulatory properties that prevent the development of inflammatory autoimmune disorders such as rheumatoid arthritis in animal models. The B-subunit, in contrast to the whole cholera toxin, is non-toxic and has no adverse effects in humans. This has sparked considerable interest in the development of such molecules as novel anti-inflammatory agents and highlighted the necessity to better understand the B-subunit's mode of action. Current theory specifies that the B-subunit mediates its immunomodulatory effects by binding and cross-linking a ubiquitous plasma membrane glycosphingolipid, GM1 ganglioside. The essential role of GM1-interaction was recently challenged by our discovery that a mutant B-subunit (H57A) was unable to modulate the immune system even though it still bound to GM1; suggesting that the B-subunits interact with another receptor (or co-receptor), and that it is this second interaction that directs the immune system to prevent development of autoimmune disease. The primary aims are to characterize the nature of B-subunit interaction with the cell membrane and to identify the co-receptor. This work has the potential to provide a new target for drug discovery and development of immunotherapeutics.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120101340
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Subversion of innate immune responses by pathogenic Escherichia coli. This project will determine how bacteria that cause diarrhoeal diseases prevent the immune system from signalling efficiently. It will provide important information not only about how the bacteria establish disease, but also provide insight into the host response in the early stages of infection.
The Role Of The Intracellular Pathogen-recognition Molecule Nod1 In The Host Response To Helicobacter Pylori Infection.
Funder
National Health and Medical Research Council
Funding Amount
$243,000.00
Summary
The report in 1982 by two Australian clinicians, Drs Marshall and Warren, of a link between a spiral-shaped bacterium, Helicobacter pylori, and stomach disease in humans was to prove one of the ground breaking discoveries of medical research in the last 20-30 years. Despite extensive studies since, including the sequencing of the entire genomes of two different H. pylori isolates, many issues relating to H. pylori disease remain unanswered. For instance, it is still not known why all infected in ....The report in 1982 by two Australian clinicians, Drs Marshall and Warren, of a link between a spiral-shaped bacterium, Helicobacter pylori, and stomach disease in humans was to prove one of the ground breaking discoveries of medical research in the last 20-30 years. Despite extensive studies since, including the sequencing of the entire genomes of two different H. pylori isolates, many issues relating to H. pylori disease remain unanswered. For instance, it is still not known why all infected individuals develop inflammation of the stomach lining, yet only a proportion (15-20%) will go on to develop severe diseases, such as peptic ulcer disease and stomach cancer. Recent work from our groups has identified the mechanism by which H. pylori induces host responses in the cells lining the stomach, the epithelial cell. The interaction of the bacterium with these cells represents its first contact with the host, and sets the scene for the development of immune responses in the stomach. From their position on the outside surfaces of epithelial cells, certain strains of H. pylori are able to deliver a bacterial component into host cells, thus triggering an inflammatory response in the latter. Curiously, a host molecule called Nod1, which is present on the inside of cells and not on the surface, acts as an internal sensor by interpreting the entry of this H. pylori component as a danger signal for the host. The aim of the project will be to characterise the resulting defence mechanisms that are induced by Nod1 in order to prevent the colonisation of the stomach by H. pylori bacteria. It is expected that this work will address questions concerning the role of host immune defence mechanisms in H. pylori infection and stomach disease. Amongst the possible public health benefits of this work will be the development of novel therapies to reduce inflammation in the stomach by blocking Nod1 responses to H. pylori bacterial components.Read moreRead less