Functional Analyses Of The Major Merozoite Surface Protein Of Malaria Parasites
Funder
National Health and Medical Research Council
Funding Amount
$70,285.00
Summary
In this project we aim to learn about the function of one of the leading malaria vaccine candidates, merozoite surface protein 1 (MSP-1). Although a promising candidate, little is known about the role of this protein in the invasion by parasites of red blood cells or of the likelihood that the parasites will adapt to avoid vaccines based on MSP-1. To address these issues we propose to use the powerful new technology of parasite transfection, that is the ability to insert DNA into parasites to sp ....In this project we aim to learn about the function of one of the leading malaria vaccine candidates, merozoite surface protein 1 (MSP-1). Although a promising candidate, little is known about the role of this protein in the invasion by parasites of red blood cells or of the likelihood that the parasites will adapt to avoid vaccines based on MSP-1. To address these issues we propose to use the powerful new technology of parasite transfection, that is the ability to insert DNA into parasites to specifically alter its genetic code. We have pioneered this technology and have developed many of the most effective tools for the process. Insight gained from these studies is likely to influence significantly the design and potential uses of MSP-1 as a vaccine to control malaria.Read moreRead less
Molecular Characterization Of The Gingipains Of Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$394,000.00
Summary
Chronic periodontitis is a bacteria-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease and pre-term birth and low birth weight. The bacterium Porphyromonas gingivalis has now been identified as a major pathogen in the development of chronic perio ....Chronic periodontitis is a bacteria-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease and pre-term birth and low birth weight. The bacterium Porphyromonas gingivalis has now been identified as a major pathogen in the development of chronic periodontitis. We have identified a major virulence factor of P. gingivalis which is an extracellular complex of proteins involved in binding and destroying host proteins. The aim of this proposal is to characterize the secretion, molecular processing and assembly of the cell surface complex using state-of-the-art proteomic techniques. This study will provide valuable insight into the molecular processes of a bacterial pathogen that leads to virulence. Detailed knowledge on the unique molecular events involved in secretion, processing and assembly of a major virulence factor will provide molecular targets for the development of specific inhibitors that may have utility as an adjunctive therapeutic and-or as part of a preventive regime or maintenance program for the control of chronic periodontitis. Further, the molecular insight that will result from this study will have broader application in the understanding of virulence factor processing of a Gram-negative pathogen that will provide paradigms for other bacterial pathogens.Read moreRead less
Development Of A Novel Bioengineered Tissue Construct For Repairing The Eye.
Funder
National Health and Medical Research Council
Funding Amount
$335,817.00
Summary
Corneal diseases are often treated using donor tissue transplants. Nevertheless, donor tissue is unsuitable for treating the peripheral or limbal margin of the cornea. We have therefore developed a way to transplant sheets of limbal tissue (epithelium) grown in the laboratory from a patient's own cells, but this tissue lacks a foundation of connective tissue that we believe is essential for sustained healing. Thus, our aim is to develop a novel limbal transplant which contains both layers.
Schistosomes are parasitic flukes that survive in the blood vessels of their human hosts for many years. More than 200 million people are infected in developing countries, and Australian travelers to these regions are often infected. As larval schistosomes mature, they undergo physiological changes in the their outer surface, the tegument, and rapidly become refractory to vigorous immune responses. In the 1960's, researchers proposed that schistosomes evade otherwise destructive immune responses ....Schistosomes are parasitic flukes that survive in the blood vessels of their human hosts for many years. More than 200 million people are infected in developing countries, and Australian travelers to these regions are often infected. As larval schistosomes mature, they undergo physiological changes in the their outer surface, the tegument, and rapidly become refractory to vigorous immune responses. In the 1960's, researchers proposed that schistosomes evade otherwise destructive immune responses by masking their presence through the adsorption of host molecules onto the parasite surface. Intriguingly, most of the molecules adsorbed by the parasite are proteins involved in immune responses, such as MHC and immunoglobulins. In order to understand the molecular basis of schistosome maturation and masking, we recently isolated a protein that binds host IgG-Fc from the surfaces of schistosomes. We hypothesise that masking proteins expressed on the surface of developing parasites interfere with the development of protective immune responses by masking the otherwise susceptible tegument. Moreover, masking proteins are ideal candidate antigens for anti-schistosome vaccines. We now propose to test this hypothesis by identifying schistosome surface proteins that acquire host immune molecules, and isolate the genes encoding these parasite masking proteins. Masking proteins will be identified using protein-based affinity methods and differentially expressed gene- and protein-based methods. Recombinant masking proteins will then be assessed as unmasking vaccines in a mouse model of schistosomiasis. Elucidation of these aims should help to unravel the widely reported enigma of schistosome masking and the long-term survival of the parasite in the human bloodstream. By unmasking these parasites from their host-derived cloak, novel methods of controlling schistosomiasis will be revealed and efforts to develop a vaccine will be greatly accelerated.Read moreRead less
Molecular Characterisation Of The Dendritic Cell Receptor Clec9a And Its Ligand Interactions
Funder
National Health and Medical Research Council
Funding Amount
$651,784.00
Summary
The immune system senses danger from infectious diseases, damaged and dead cells. We identified a danger receptor, Clec9A, on a specialised cell type of the immune system in mice and humans. Clec9A recognizes and induces immunity to dangerous dead cells. Delivering vaccines to Clec9A improves vaccine responses. We will investigate how Clec9A recognises and reacts to danger, and how we can mimic this recognition to improve vaccine design.
Characterisation Of The Role & Biomarker Potential Of The Novel Cell Surface Protein TTYH2 In Renal Cell Carcinoma
Funder
National Health and Medical Research Council
Funding Amount
$489,000.00
Summary
Renal cell carcinoma is the most common cancer of the kidney. One-third of patients upon first diagnosis have secondary tumour sites already within their body as well as new treatment approaches for more advanced disease making them very difficult to cure. An early specific test for this cancer is urgently needed. Our group has identified a new gene called TTYH2 which is highly expressed by renal cell carcinoma tissue samples but not in normal kidney tissues. In this study, we intend to look at ....Renal cell carcinoma is the most common cancer of the kidney. One-third of patients upon first diagnosis have secondary tumour sites already within their body as well as new treatment approaches for more advanced disease making them very difficult to cure. An early specific test for this cancer is urgently needed. Our group has identified a new gene called TTYH2 which is highly expressed by renal cell carcinoma tissue samples but not in normal kidney tissues. In this study, we intend to look at the expression of TTYH2 in more clinical samples to determine if TTYH2 will be a useful bio-marker for this cancer. We are also studying the function of this protein in renal cell carcinoma cells to identify the exact role that TTYH2 performs in cancer development and progression. Finally we will look at what other proteins are interacting with TTYH2 in kidney cancer cells. These latter studies will help us to understand the disease process better and may help us design new treatment methods.Read moreRead less
Structure And Interactions Of A Disordered Malaria Surface Protein: Implications For Antigenicity
Funder
National Health and Medical Research Council
Funding Amount
$511,020.00
Summary
Malaria is responsible for around 2 million deaths annually, many in children under 5 years of age. Merozoite surface protein 2 (MSP2) from Plasmodium falciparum is being developed as a vaccine candidate. We will investigate the structure of MSP2 in various environments, including when bound to inhibitory antibodies. Key goals are to understand how the disordered structure of MSP2 affects its interaction with the host immune system and how that information can be used to design better vaccines.