Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contr ....Imaging the generation and recall of protective antiviral immune responses in vivo. Our understanding of the in vivo dynamics of cellular immune responses to infectious diseases is poor. This project will utilise advanced intravital imaging combined with novel tools to dissect the cellular events involved in the generation and recall of T cell responses to localised virus infection, combined with a detailed functional analysis of the lymphoid organ stroma. Such fundamental information will contribute to the development of new generation vaccines and therapies to protect against tissue-specific infectious diseases, cancers and autoimmune diseases.Read moreRead less
Unlocking malaria invasion by ultraresolution microscopy. This project describes the microscopic analysis of malaria-causing parasites invading human blood cells. The project aims to better understand how this invasion works and to understand how it might be inhibited.
Molecular dissection of malaria parasite motility and host-cell invasion across the lifecycle. Malaria parasites move in a unique way, gliding across cell surfaces and infecting host cells using a unique molecular motor. This research aims to understand the molecular mechanics behind parasite movement and use this to develop novel drugs that might throw a spanner in the parasite motor, blocking movement and thereby preventing malaria disease.
Investigating the molecular basis of T-cell receptor cross-reactivity. This project will explore the basis of unexpected immune reactions whereby the immune system mistakes one molecular structure for another, a phenomenon known as cross-reactivity. This project will examine how often this is due to molecular mimicry, potentially explaining why immune T cells sometimes react inappropriately to different agents.
Cellular Organisation of Protective Immune Responses. Our immune system consists of a task force of white blood cells that coordinate to defeat invading pathogens. Research has revealed a cell receptor, CXCR3, controls immune cell interactions, which determine immune control and protection during initial cell activation and viral infection. This project will use a multi-disciplinary approach combining viral immunology, unique mouse models, advanced imaging, and bioinformatic analyses to dissect ....Cellular Organisation of Protective Immune Responses. Our immune system consists of a task force of white blood cells that coordinate to defeat invading pathogens. Research has revealed a cell receptor, CXCR3, controls immune cell interactions, which determine immune control and protection during initial cell activation and viral infection. This project will use a multi-disciplinary approach combining viral immunology, unique mouse models, advanced imaging, and bioinformatic analyses to dissect the cellular conversations that underpin immune protection. Revealing the mechanisms of cellular interactions during an immune response will have a major impact on development of targeted vaccines, and therapeutics (particularly for chronic infections and cancer), which are major health burdens.Read moreRead less
Multifunctional biodegradable nanoparticles for enhanced DNA vaccine delivery. DNA vaccine, which shows better immunological and economic merits than conventional vaccines, suffers clinical failure due to the difficulty of delivering intact DNA molecules to relevant cells. This project seeks to develop smart polymer nanospheres to protect the DNA molecules from premature degradation in order to improve its efficacy.
Investigation of a Novel Protein Implicated in Phosphate Metabolism in Bacteria. Phosphate is an important nutrient for all forms of life on Earth. A novel bacterial protein has been identified that appears to be important for the uptake or processing of phosphate, since mutants lacking the protein grow poorly inside certain cells of the human immune system (where phosphate levels are low) and in media containing low phosphate. The aims of this project are: to determine the role of the protein b ....Investigation of a Novel Protein Implicated in Phosphate Metabolism in Bacteria. Phosphate is an important nutrient for all forms of life on Earth. A novel bacterial protein has been identified that appears to be important for the uptake or processing of phosphate, since mutants lacking the protein grow poorly inside certain cells of the human immune system (where phosphate levels are low) and in media containing low phosphate. The aims of this project are: to determine the role of the protein by examining all phosphate containing molecules in our mutants; to determine its location in bacteria and functional domains; to identify other affected genes in our mutants; and, to find proteins that interact with this new protein. This project expects to demonstrate the importance of this protein in phosphate metabolism in bacteria.Read moreRead less
Programmed cell death in host-microbe interactions. This project aims to address how host cell death, as part of the immune defence system, controls invading microbes. By following host-microbe interactions at high resolution, the project will generate new knowledge in the area of infection and immunity based on an interdisciplinary approach to discover new cell death factors. The expected outcome of this project will enhance the imaging capacity and develop new technologies in Australia by buil ....Programmed cell death in host-microbe interactions. This project aims to address how host cell death, as part of the immune defence system, controls invading microbes. By following host-microbe interactions at high resolution, the project will generate new knowledge in the area of infection and immunity based on an interdisciplinary approach to discover new cell death factors. The expected outcome of this project will enhance the imaging capacity and develop new technologies in Australia by building on international collaborations, providing significant benefits to the health of the community and potential to develop innovative applications in biomedical industries.Read moreRead less
Molecular basis of synergy between PIs and defensins against fungi. The plant defensin nicotinamide adenine dinucleotide dehydrogenase subunit 1 (NaD1) has potent antifungal activity against agricultural and human pathogens and has potential in the treatment of serious diseases that affect crop production and human health. NaD1 has been found to permeabilise membranes and allows entry of other molecules into the fungal cytoplasm. While screening for molecules that enhance the activity of defensi ....Molecular basis of synergy between PIs and defensins against fungi. The plant defensin nicotinamide adenine dinucleotide dehydrogenase subunit 1 (NaD1) has potent antifungal activity against agricultural and human pathogens and has potential in the treatment of serious diseases that affect crop production and human health. NaD1 has been found to permeabilise membranes and allows entry of other molecules into the fungal cytoplasm. While screening for molecules that enhance the activity of defensins a number of proteinase inhibitors were identified that act synergistically with NaD1. This project aims to identify the molecular basis of this synergy which is expected to lead to better control of fungal diseases of crops and in humans.Read moreRead less
Host-pathogen interactions: the role of mimicry. The proposed research program, using a combination of structure and functional analysis will provide insight into the mechanism of nucleotide hydrolysis by the enzymes NTPDases. This study will not only improve our fundamental understanding of NTPDase action but could lead to the rational design of antimicrobials.